Journal of Men's Health. 2026; 22(7): 1-9. doi: 10.22514/jomh.2026.055
Review

Metabolic–endocrine and epigenetic mechanisms linking obesity to male infertility: a narrative review

Guoqing Zhang1, Mukhri Hamdan1,*,

1Department of Obstetrics and Gynecology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

*Corresponding Author(s):mukhri@um.edu.my (Mukhri Hamdan)

History Submitted: 23 January 2026 | Accepted: 03 April 2026 | Published: 30 July 2026
Copyright:  ©2026 The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

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Abstract

Obesity is a globally prevalent chronic condition and a well-recognized metabolic disorder associated with systemic metabolic dysregulation and various diseases. In recent years, growing evidence suggests that obesity also plays a significant role in male reproductive dysfunction. This narrative review was based on a targeted literature search primarily conducted in PubMed using combinations of keywords. Priority was given to recent high-quality clinical and experimental studies, and seminal earlier studies and additional relevant references from key articles were also included. Current evidence indicates that obesity impairs male reproductive health through multiple interconnected mechanisms, including adipokine dysregulation, chronic inflammation, insulin resistance, endocrine imbalance, impaired spermatogenesis, and sperm epigenetic remodeling. However, findings regarding paternal obesity and assisted reproductive technology (ART) outcomes remain inconsistent, although some studies suggest potential associations with adverse offspring outcomes. Lifestyle modification and pharmacological interventions can partially improve obesity-associated reproductive impairment, underscoring male obesity as a modifiable risk factor. In summary, by integrating metabolic, endocrine, and epigenetic perspectives, this review provides a mechanistic framework to better understand obesity-related male infertility and to inform future clinical and translational research.

Keywords:ObesityMale fertilitySperm epigeneticsEndocrine dysfunction
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Cite this article

Guoqing Zhang, Mukhri Hamdan. Metabolic–endocrine and epigenetic mechanisms linking obesity to male infertility: a narrative review. Journal of Men's Health. 2026; 22(7): 1-9. doi: 10.22514/jomh.2026.055

1. Introduction

Obesity is a globally prevalent chronic metabolic disorder and has escalated into a major public health concern over recent decades. According to the World Health Organization (WHO), the prevalence of obesity continues to rise globally, which contributes significantly to the burden of cardiovascular diseases, type 2 diabetes mellitus (T2DM), and various cancers [1]. Since 1975, the global prevalence of obesity has nearly tripled, and it is expected to reach 1.02 billion adults (18% of the population) by 2030 [2].

In parallel, a notable global decline in male fertility has been documented, with studies reporting reduced sperm counts and impaired semen quality [3], and increased dependence on assisted reproductive technologies (ART) [4]. This downward trend has prompted increasing attention to modifiable risk factors, such as obesity. Mechanistically, obesity-induced hormonal imbalance [5, 6, 7], inflammation, and oxidative stress may jointly disrupt the hypothalamic–pituitary–testicular (HPT) axis and impair spermatogenesis [8, 9].

Beyond these direct effects, recent studies have highlighted the potential for transgenerational consequences of paternal obesity via epigenetic modifications in sperm [8, 10, 11, 12]. At the molecular level, paternal obesity has been shown to reduce chromatin accessibility and alter the histone landscape in sperm, potentially affecting offspring metabolic and reproductive outcomes [11, 12]. While some studies have examined the association between paternal obesity and ART success, the relationship remains inconclusive, likely due to heterogeneous methodologies and inconsistent definitions of obesity [13, 14].

Despite these advances, existing research remains fragmented. Most studies focus on isolated mechanisms or clinical endpoints without integrating molecular, clinical, and intergenerational perspectives. Additionally, there is no consensus on how to assess obesity effectively in reproductive studies, many rely solely on body mass index (BMI), which may not fully capture central adiposity or metabolic dysfunction. Moreover, while animal studies support the role of epigenetic inheritance, human data remain sparse and largely observational.

In this narrative review, we conducted a targeted literature search to synthesize recent experimental and clinical evidence on the multifaceted effects of obesity on male reproductive function. Unlike previous reviews that focus on isolated clinical or metabolic outcomes, this review integrates endocrine dysregulation, sperm epigenetic remodeling, and potential intergenerational effects to provide a comprehensive mechanistic framework linking obesity to male infertility.

2. Literature search strategy

This narrative review was based on a targeted literature search primarily conducted in PubMed. The search focused on studies related to obesity and male reproductive dysfunction using combinations of keywords derived from the core topics of this review, including “obesity”, “male infertility”, “sperm epigenetics”, and “endocrine dysfunction”.

Priority was given to recent high-quality studies published in peer-reviewed journals, including clinical studies, experimental studies, and influential review articles. Seminal earlier studies were also included when relevant. Additional references were identified by screening the reference lists of key publications to ensure comprehensive coverage of important studies in this field.

3. Definitions and diagnoses of obesity

Obesity is the excessive accumulation of fat in various parts of the body or organs [15]. According to WHO, obesity is defined as a BMI ≥30 kg/m2 (http://www.who.int). However, it is important to consider that BMI is only useful as a screening tool because it is not a direct measure of adiposity. Therefore, as a complementary criterion to BMI, assessment of Waist Circumference (WC) is helpful for evaluating cardiometabolic disease risk [16].

WHtR (Waist-to-Height Ratio) and WHT-5R (WC divided by height0.5) are two anthropometric predictors of fat distribution. WHtR has been shown to be a better surrogate measure of body adiposity compared with other anthropometric indexes in adults, adolescents, and children [17]. For WHT-5R, it has been proposed as a suitable index for screening for metabolic disease [18].

Advanced imaging methods, such as dual X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI), can accurately assess fat mass and distribution [19, 20], but high costs of advanced imaging methods limit routine use [21]. In contrast, bioelectrical impedance analysis (BIA) and digital anthropometry provide quick, noninvasive, and affordable alternatives [22], while three-dimensional (3D) optical and two-dimensional (2D) photographic systems offer precise digital assessments of body composition [23].

In summary, although BMI is still widely used as an easy, quick, low-cost, and reproducible method, BMI alone is insufficient to evaluate obesity and body composition. Therefore, clinical practice recommends combining WC, WHtR, and more precise body composition analysis methods to improve the accuracy and effectiveness of obesity diagnosis and management.

4. Global burden of high BMI

High BMI has increasingly become a significant public health risk factor, contributing to a growing burden of disease worldwide. It accounts for 129 million Disability-Adjusted Life Years (DALYs) and is responsible for 3.7 million deaths globally, ranking as the seventh leading risk factor for attributable DALYs [24]. Apart from increasing the incidence of various chronic diseases, high BMI also imposes a substantial burden on healthcare systems, underscoring the urgent need for effective prevention and management strategies at a global level.

The burden of diseases linked to high BMI is primarily driven by non-communicable diseases (NCDs), notably diabetes, nephrological, and cardiovascular diseases [24]. Although a direct relationship between high BMI and male reproductive health is not well established, these metabolic comorbidities are strongly associated with impaired reproductive function [25, 26, 27].

From 2010 to 2021, DALYs related to high BMI increased by 44.6%, and its ranking raised from eighth in 2010 to seventh in 2021, reflecting the growing severity of overweight and obesity issues worldwide [28]. Interestingly, DALYs caused by high BMI are slightly higher in men than in women [29]. Given the growing global burden, understanding how obesity impacts male reproductive health is increasingly important.

5. Consequences of obesity on male reproductive health

5.1 Obesity as a metabolic disorder: pathophysiological insights

Metabolic homeostasis plays a crucial role in reproductive health, yet obesity undermines this equilibrium through multiple mechanisms [30]. Obesity disrupts metabolic homeostasis through adipokine dysregulation, chronic inflammation, and insulin resistance, which may directly impair sperm function and the testicular microenvironment [4, 31].

Adiponectin is negatively associated with body fat mass and positively associated with total sperm count, sperm concentration, as well as the percentage of spermatozoa with normal morphology [32, 33]. In addition, adiponectin can enhance insulin sensitivity, regulate food intake, and exert anti-inflammatory effects [34]. Individuals with obesity have increased leptin levels and leptin resistance, which in turn affects sperm motility and sperm morphology [35]. Resistin and irisin are negatively correlated with BMI and are suggested to exert anti-inflammatory effects [32, 36].

Chemerin has emerged as a metabolically relevant adipokine that may contribute to obesity-related male reproductive dysfunction [37, 38]. An observational study (n = 4101) demonstrated that circulating chemerin levels were positively associated with BMI, WC, and WHtR [39]. Chemerin is mainly secreted by the liver and is found to reduce sperm count and motility in vitro in roosters [40]. In clinical studies of obese men, altered circulating or seminal levels of chemerin/adipokine profiles have been associated with poorer reproductive hormone balance and/or semen quality [41].

Obesity-induced chronic inflammation directly impairs male reproductive function. Obesity-induced inflammation is an important pathogenic mediator of many metabolic diseases, including insulin resistance, T2DM, and cardiovascular diseases [42, 43, 44]. Clinical evidence indicates that obese men exhibit increased tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) levels in seminal plasma, and these cytokines are positively correlated with BMI, but inversely correlated with sperm concentration and motility [45]. Experimental studies further show that obesity-induced inflammation disrupts Sertoli-cell function, increasing reactive oxygen species (ROS) production, and promoting blood-testis barrier injury, thereby impairing spermatogenesis [46]. In addition, obesity-associated activation of the proprotein convertase subtilisin/kexin type 9–NLR family pyrin domain containing 3 (PCSK9–NLRP3) inflammasome in Leydig cells has been shown to reduce testosterone production and disrupt spermatogenesis in high-fat-diet mice [47].

Additionally, insulin resistance may directly impair male reproductive function. In a rat model, diet-induced hyperinsulinemia and insulin resistance were accompanied by reduced sperm motility, and decreased testosterone levels [48]. In obese men, increased serum and seminal insulin concentrations have been reported together with reduced sperm concentration, lower sperm vitality, and increased sperm DNA fragmentation [49]. Moreover, homeostatic model assessment of insulin resistance (HOMA-IR) has been negatively correlated with serum testosterone, semen volume, and the percentage of progressively motile sperm. These findings support a direct association of obesity-related insulin resistance with impaired sperm quality and a less favorable testicular endocrine environment for spermatogenesis.

Together, these findings indicate that adipokine imbalance, chronic inflammation, and insulin resistance are direct metabolic mechanisms linking obesity to impaired spermatogenesis, sperm dysfunction, and testicular microenvironmental injury.

5.2 Obesity and HPT axis

The HPT axis regulates the spermatogenesis in the testis and synthesis of testosterone in humans and animals [50, 51]. Concerning gonadotropin-releasing hormone (GnRH) secretion, KNDy (kisspeptin/neurokinin B/dynorphin A) is considered as a crucial regulator and is co-secreted by neurons of the hypothalamus [52]. GnRH in turn stimulates pituitary secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [52, 53]. FSH and LH act on specific gonadal cells to stimulate the secretion of testosterone, estrogen, and gametogenesis. Testosterone is an important anabolic hormone, circulating as albumin-bound or sex hormone-binding globulin-bound (SHBG), while only a minor fraction is free and bioactive [54].

FSH primarily acts to stimulate testicular Sertoli cell function. These cells promote spermatogenesis, as each cell is able to support the maturation of 2–4 germ cells on average [55]. Testosterone has a synergistic effect with the FSH to support spermatogenesis [56]. FSH supports germ cells until the stage of spermatocyte, while it synergistically supports spermatids to differentiate into spermatozoa together with intratubular testosterone [57]. LH triggers the testosterone synthesis in Leydig cells, and the proliferation of Leydig cells depends on FSH [58, 59]. LH beta-null male mice are reported to be infertile, combined with defects in Leydig cells and suppression of testosterone level [60]. Circulating sex hormone concentrations, metabolic disorders, and environmental factors directly or indirectly regulate the HPT axis.

Regarding the effects of increased body weight on serum steroid hormone levels, a recent systematic review concludes that obesity is negatively correlated with total testosterone and SHBG levels, while positively correlated with estrogen levels [61]. These hormonal changes are partly attributable to the excessive conversion of testosterone into 17 beta-estradiol by adipocytes [62]. Elevated 17β-estradiol may further modulate the expression of the kisspeptin gene, which regulates pulsatile GnRH secretion to inhibit the HPT axis [63, 64].

Beyond this aromatase-dependent mechanism, obesity-related metabolic disturbances likely act upstream of endocrine dysfunction, rather than representing an independent parallel pathway. Hyperleptinemia accompanied by leptin resistance may impair hypothalamic kisspeptin/GnRH signaling [65, 66], whereas insulin resistance is closely linked to suppression of the HPT axis and low-testosterone states [67, 68]. In addition, chronic low-grade inflammation may impair Leydig-cell steroidogenesis through pro-inflammatory cytokines [69]. Adipokine imbalance may further contribute to this process: beyond leptin excess, experimental studies suggest that adiponectin signaling can modulate hypothalamic GnRH/KiSS-1 metastasis suppressor (KISS1) activity and pituitary LH release [70, 71, 72].

5.3 Obesity and testicular dysfunction

Due to the excess aromatase activity in many men with obesity, obese males often present with functional hypogonadism [62]. It is characterized by inappropriately normal levels of gonadotropins despite low testosterone levels [73]. Combined with the inhibition of SHBG on testosterone function, the lower level and lower activity of circulating testosterone facilitate the accumulation of body fat. Thus, a vicious circle of obesity, low testosterone levels, and hypogonadism is formed. Due to its inhibitory effect on testicular function, aromatase inhibitors have been used in hypogonadism treatment.

A recent observational study investigating the relationship between BMI and erectile dysfunction (ED) risk found that obese individuals had a 1.3-fold greater risk of ED than normal-weight individuals [74]. This association suggests that metabolic abnormalities accompanying obesity, such as insulin resistance and hyperglycemia, may play a pivotal role in the pathophysiology of erectile dysfunction.

Hyperglycemia triggers a cascade of cellular events that increases the production of ROS and oxygen-derived free radicals, contributing to increased oxidative stress. Additionally, hyperglycemia can lead to the glycation of penile cavernosal tissue, compromising collagen production and potentially contributing to ED [75]. Hyperglycemia, along with obesity interfering steroidogenesis in Leydig cells by proinflammatory cytokines, like IL-1β, IL-6 and TNF-α, can lead to ED [76]. Testosterone supplementations are encouraged by European Society of Endocrinology to improve erectile function [77].

It is noted that the prevalence of obesity has coincided with a steady decline in sperm quality worldwide, particularly in sperm counts over the past 50 years [3, 78, 79]. Obesity is also associated with a pro-inflammatory environment derived from adipose tissue that is likely detrimental to sperm function and spermatogenesis [80, 81]. Obesity-associated co-morbidities, such as metabolic syndrome and increased scrotal temperature in case of increased abdominal adiposity, are amongst other causal mechanisms impacting the male reproductive axis and semen parameters [82, 83, 84, 85].

5.4 Obesity and sperm epigenetics

Beyond hormonal mechanisms, obesity can exert heritable effects via sperm epigenetic reprogramming. Animal studies have shown that paternal obesity impaired the structure of testicular seminiferous tubules and reduced the number of epididymal sperm in offspring [86, 87]. These findings highlight the importance of further investigating the underlying mechanisms.

Insulin resistance and inflammation should be considered an upstream metabolic disturbance linked to sperm epigenetic remodeling. Sperm from obese men with abnormal glucose metabolism exhibit altered small non-coding RNA expression and DNA methylation patterns, and these methylation signatures can be dynamically remodeled after substantial weight loss [88]. Experimental studies further show that paternal high-fat diet induces impaired glucose tolerance and insulin tolerance, together with altered sperm tsRNA profiles [89]. Moreover, paternal obesity has been associated with changes in sperm histone H3 lysine 4 trimethylation (H3K4me3) enrichment at loci related to metabolic and developmental regulation [9]. In parallel, inflammation appears to be one of the mediating pathways, as paternal inflammation has been shown to alter sperm 5′-tsRNAs, whereas anti-inflammatory treatment in high-fat-fed sires reduces specific sperm tsRNAs and partially improves offspring metabolic phenotypes [90, 91].

There is mounting evidence that obesity in males is associated with altered sperm DNA methylation and may contribute to offspring phenotypes [92, 93]. A human study in Germany collected sperm from 294 participants at the Fertility Center Wiesbaden, fetal cord blood samples were successfully obtained from 103 pregnancies resulting in live births after ART [94]. In this study, maternally expressed gene 3-intergenic (MEG3-IG) differentially methylated region (DMR), sperm DNA methylation, and MEG3-IG DMR cord blood DNA methylation in male offspring showed a positive correlation with male BMI [94]. Hypoxia inducible factor 3 subunit alpha (HIF3A) cord blood DNA methylation in male offspring showed a positive correlation with the paternal BMI, while insulin-like growth factor 2 (IGF2) DMR0 in female offspring showed a negative correlation with the paternal BMI [94]. Another study investigated 67 men and found that overweight/obese individuals had differences in mature spermatozoa DNA methylation profiles. They identified 3264 cytosine-phosphate-guanine (CpG) sites in human sperm that correlated significantly with BMI [95].

As a subtype of sncRNA, tRNA-derived small RNAs (tsRNAs) are known to be abundant in mammalian sperm, including humans [96]. Human sperm are acutely sensitive to nutrient flux, both in respect of sperm motility and changes in sperm tsRNA (primarily from mitochondrial origin: mt-tRNAs), and a 1-week sugar-rich dietary intervention was shown to increase mitochondrial tsRNAs while reducing sperm motility [97]. In mice, acute paternal HFD-feeding leads to impaired glucose homeostasis in male offspring via mt-tRNAs [98]. Mechanistically, increased accumulation of mt-tRNAs is transcribed and fragmented in mature spermatozoa, which can be transferred to the oocyte at fertilization and results in early altered transcription of genes important for oxidative metabolism, shown to predispose to adult-onset glucose intolerance [98].

Regarding the sperm proteome, a recent study identified 2034 proteins by analyzing sperm samples from healthy (BMI ≤25 kg/m2, n = 5) and obese men (BMI ≥30 kg/m2, n = 5) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) [99]. They found significantly altered abundances in 27 of those proteins, which are involved in a variety of biological processes, including oxidative stress (glutathione synthetase, GSS; NADH:ubiquinone oxidoreductase core subunit S2, NDUFS2; jagunal homolog 1, JAGN1), inflammation (suppressor of G2 allele of skp1 homolog 1, SUGT1; leukotriene A4 hydrolase, LTA4H), translation (eukaryotic translation initiation factor 3 subunit F, EIF3F; eukaryotic translation initiation factor 4A2, EIF4A2; casein kinase 1 gamma 1, CSNK1G1), DNA damage repair (ubiquitin protein ligase E3A 4, UBEA4), and sperm function (N-ethylmaleimide-sensitive factor attachment protein alpha, NAPA; arginyl aminopeptidase, RNPEP; barrier-to-autointegration factor 2, BANF2) [99]. In addition, a prospective study performed seminal plasma proteomic analysis in eutrophic (BMI 18.5–24.9 kg/m2, n = 20) and obese men (BMI ≥30 kg/m2, n = 27), and identified 69 differentially expressed proteins between the two groups [100]. Importantly, these proteomic alterations were accompanied by impaired sperm morphology, reduced acrosome integrity, decreased mitochondrial activity, and increased sperm DNA fragmentation in the obese group [100]. It has been demonstrated that sperm telomere length (STL) is significantly shorter in obese individuals (n = 32) compared to normal-weight controls [101]. And this telomere shortening turns out to be correlated negatively with age, BMI, DNA fragmentation index (DFI), the percentage of sperm with immature chromatin, and intracellular reactive ROS levels [101].

In summary, the impact of paternal obesity is not limited to the individuals themselves, but may also be transmitted to offspring through epigenetic modifications in sperm. Therefore, further elucidation of the sperm epigenetic mechanisms involved in the transgenerational inheritance of obesity is of great significance for understanding hereditary risks associated with obesity and guiding clinical preventive strategies.

5.5 Clinical implications and interventions

Given the adverse effects of obesity on sperm parameters and testicular function, increasing attention has been paid to its potential impact on ART outcomes. A largely retrospective cohort study in China (n = 11,191) assessed the effect of female and male overweight/obesity on In Vitro Fertilization (IVF) outcomes individually and in combination. Although the combined overweight/obesity was associated with fewer available and high-quality embryos, as well as lower fertilization and normal fertilization rates, no significant association was observed between male overweight/obesity alone and clinical pregnancy rate (CPR), live birth rate (LBR), or abortion rate [102]. Similar results are reported in a more recent retrospective cohort study of 2075 oligozoospermia and/or asthenospermia males in which obesity was not associated with fertilization, in vitro embryonic development, and pregnancy outcomes [103]. However, they show that paternal BMI is positively correlated with macrosomia, large for gestational age (LGA), and very LGA [103].

However, the reported effects of paternal obesity on ART outcomes remain inconsistent. In a recent observational study, infertile individuals (n = 296) were categorized into three groups by WC [104]. They found that males with a WC larger than 100.5 cm had a 33.5% lower total sperm count than males with a WC of 90 cm [104]. Additionally, WC is negatively correlated with the probabilities of implantation, clinical pregnancy, and live birth rate during ART treatment [104]. However, when using BIA and BMI as adiposity measurement metrics, paternal obesity shows no meaningful impact on embryologic or clinical results on IVF (including blastocyst formation rates, miscarriage rates, sustained implantation rates, and live birth rates) [105]. These conflicting findings may partly reflect methodological heterogeneity across studies, particularly differences in obesity assessment, sample size, patient selection, and study design [13, 103, 106].

A prior systematic review and meta-analysis of 30 studies and 115,158 participants has indicated that obese men are more likely to experience infertility than their nonobese counterparts [107]. A major challenge of obesity treatment is weight regain after weight loss. This has prompted increasing interest in whether effective weight-loss interventions can also improve male reproductive outcomes.

Recently, a randomized, head-to-head, placebo-controlled trial was designed and enrolled obese adults whose BMI was 32–43 (did not have diabetes) [108]. These adults (n = 195) underwent an 8-week low-calorie diet and had a mean decrease of 13.1 kg in body weight [108]. After that, participants were randomly assigned for 1 year to one of four strategies: placebo plus habitual activity (placebo), exercise training plus placebo (exercise), the Glucagon Like Peptide 1 (GLP-1) analogue liraglutide plus usual activity (liraglutide), exercise training plus liraglutide (combination) [108]. In the first year, all the active-treatment strategies led to a decreased body weight and body-fat percentage, and additional health benefits, such as improvements in the insulin sensitivity, glycated hemoglobin level, cardiorespiratory fitness, emotional well-being, and physical functioning were found in combination group [108]. Further research in semen parameters indicates that adult men who delivered semen samples (n = 56, aged 18–65) lost on average 16.5 kg body weight during the 8-week low-calorie diet, which increased sperm concentration 1.49-fold and sperm count 1.41-fold [20]. Moreover, these improvements in men who maintained the weight loss were maintained for 1 year, but not in men who regained weight [20].

Although clinical management of obesity remains challenging, exercise combined with weight-loss medications may be an effective treatment for weight loss and has potential benefits for obesity-related reproductive disorders. To visually summarize the multifactorial mechanisms linked to obesity in male infertility and highlight potential intervention targets, an integrated mechanistic framework is presented in Fig. 1.

Integrated metabolic-endocrine-epigenetic framework linking obesity and male infertility and potential interventions. Obesity induces interconnected metabolic disturbances including adipokine dysregulation, chronic inflammation, and insulin resistance (inner circle). These upstream mechanisms disrupt the hypothalamic–pituitary–testicular axis, impair testicular function, and induce sperm epigenetic alterations, ultimately contributing to male infertility (outer circle). Lifestyle interventions, pharmacological treatments, and assisted reproductive technologies may partially mitigate these effects. GnRH: gonadotropin-releasing hormone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; GLP-1: Glucagon Like Peptide 1; TNF-α: tumor necrosis factor alpha; IL-6: Interleukin-6; NLRP3: NLR family pyrin domain containing 3.

Fig. 1.Integrated metabolic-endocrine-epigenetic framework linking obesity and male infertility and potential interventions. Obesity induces interconnected metabolic disturbances including adipokine dysregulation, chronic inflammation, and insulin resistance (inner circle). These upstream mechanisms disrupt the hypothalamic–pituitary–testicular axis, impair testicular function, and induce sperm epigenetic alterations, ultimately contributing to male infertility (outer circle). Lifestyle interventions, pharmacological treatments, and assisted reproductive technologies may partially mitigate these effects. GnRH: gonadotropin-releasing hormone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; GLP-1: Glucagon Like Peptide 1; TNF-α: tumor necrosis factor alpha; IL-6: Interleukin-6; NLRP3: NLR family pyrin domain containing 3.

6. Strengths and limitations

This review provides a comprehensive overview of the multifaceted impact of obesity on male reproductive health, encompassing key mechanisms, such as endocrine disruption, inflammatory responses, adipokine regulation, and epigenetic alterations. It highlights both the direct and transgenerational effects of obesity on fertility. Moreover, the review emphasizes the clinical relevance of body composition assessment tools beyond BMI, as well as the value of lifestyle interventions, offering theoretical support for future research and clinical strategies.

The included studies vary considerably in design, population characteristics, and methods of obesity assessment, which limits the comparability and generalizability of the conclusions. In addition, much of the mechanistic evidence is derived from animal or in vitro studies, and clinical validation remains insufficient. Research on ART outcomes and long-term offspring health in the context of male obesity is still limited. As a narrative review, there is also an inherent risk of selection bias in the literature included.

7. Conclusions

Obesity is increasingly recognized as a multifactorial metabolic disorder that negatively impacts male reproductive health. Current evidence suggests that obesity impairs the HPT axis, disrupts steroid hormone balance, and interferes with spermatogenesis and sperm function through interconnected mechanisms involving adipokine dysregulation, chronic inflammation, insulin resistance. In addition, obesity may exert potential transgenerational effects through sperm epigenetic alterations, including changes in DNA methylation, small non-coding RNAs, and chromatin-related markers.

Although the association between male obesity and ART outcomes remains inconsistent, obesity should still be regarded as an important and modifiable risk factor in reproductive medicine. Future studies should adopt more comprehensive measures of adiposity beyond BMI and further clarify the integrated metabolic, endocrine, inflammatory, and epigenetic pathways linking obesity to male infertility. In clinical management, attention should be paid not only to weight reduction and metabolic improvement, but also to the potential reproductive and transgenerational consequences of obesity. A better understanding of these mechanisms may help refine prevention strategies and improve reproductive outcomes for affected individuals and future generations.

Abbreviations

2D, two-dimensional; 3D, three-dimensional; ART, assisted reproductive technology; BANF2, BANF family member 2; BIA, Bioelectrical Impedance Analysis; BMI, Body Mass Index; CpG, cytosine-phosphate-guanine; CPR, Clinical Pregnancy Rate; CSNK1G1, casein kinase 1 gamma 1; CT, computed tomography; DALYs, Disability-Adjusted Life Years; DFI, DNA Fragmentation Index; DMR, differentially methylated region; DXA, Dual X-ray Absorptiometry; ED, Erectile Dysfunction; EIF3F, eukaryotic translation initiation factor 3 subunit F; EIF4A2, eukaryotic translation initiation factor 4A2; FSH, Follicle-Stimulating Hormone; GLP-1, Glucagon Like Peptide 1; GnRH, Gonadotropin-Releasing Hormone; GSS, glutathione synthetase; H3K4me3, histone H3 lysine 4 trimethylation; HIF3A, hypoxia inducible factor 3 subunit alpha; HOMA-IR, homeostatic model assessment of insulin resistance; HPT axis, Hypothalamic–Pituitary–Testicular Axis; IGF2, insulin-like growth factor 2; IL-6, Interleukin-6; IVF, In Vitro Fertilization; JAGN1, jagunal homolog 1; KISS1, KiSS-1 metastasis suppressor; KNDy, kisspeptin/neurokinin B/dynorphin; LBR, live birth rate; LC-MS/MS, liquid chromatography–tandem mass spectrometry; LGA, large for gestational age; LH, Luteinizing Hormone; LTA4H, leukotriene A4 hydrolase; MEG3-IG, MEG3 intergenic differentially methylated region; MRI, Magnetic Resonance Imaging; NAPA, NSF attachment protein alpha; NCDs, non-communicable diseases; NDUFS2, NADH, ubiquinone oxidoreductase core subunit S2; PCSK9–NLRP3, proprotein convertase subtilisin/kexin type 9–NLR family pyrin domain containing 3; ROS, reactive oxygen species; RNPEP, arginyl aminopeptidase; SHBG, Sex Hormone-Binding Globulin; STL, Sperm Telomere Length; SUGT1, SGT1 assembly cochaperone of MIS12 kinetochore complex; T2DM, Type 2 Diabetes Mellitus; TNF-α, tumor necrosis factor alpha; tsRNA, tRNA-derived Small RNA; UBEA4, ubiquitination factor E4A; WC, Waist Circumference; WHO, World Health Organization; WHtR, Waist-to-Height Ratio.

Availability of data and materials

Not applicable.

Author contributions

GQZ—drafted and revised the manuscript. MH—communicated with the journal and editorial office during the submission process. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

References

World Health Organization. Obesity and overweight. 2025. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (Accessed: 08 December 2025).

[Google Scholar]

NCD Risk Factor Collaboration. Obesity prevalence, body-mass index 2023. 2023. Available at: https://ncdrisc.org/obesity-prevalence-ranking.html (Accessed: 02 November 2023).

[Google Scholar]

Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Jolles M, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. Human Reproduction Update. 2023; 29: 157–176.

[Google Scholar]

Cannarella R, Crafa A, Curto R, Condorelli RA, La Vignera S, Calogero AE. Obesity and male fertility disorders. Molecular Aspects of Medicine. 2024; 97: 101273.

[Google Scholar]

Choubey M, Nikolettos N. Editorial: adipose tissue and adipokines: their roles in human reproduction. Frontiers in Endocrinology. 2024; 15: 1497744.

[Google Scholar]

Aisike G, Kuerbanjiang M, Muheyati D, Zaibibuli K, Lv MX, Han J. Correlation analysis of obesity phenotypes with leptin and adiponectin. Scientific Reports. 2023; 13: 17718.

[Google Scholar]

Obaideen M, Önel T, Yıldırım E, Yaba A. The role of leptin in the male reproductive system. Journal of the Turkish German Gynecological Association. 2024; 25: 247–258.

[Google Scholar]

Lismer A, Dumeaux V, Lafleur C, Lambrot R, Brind’Amour J, Lorincz MC, et al. Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring. Developmental Cell. 2021; 56: 671–686.e6.

[Google Scholar]

Pepin AS, Lafleur C, Lambrot R, Dumeaux V, Kimmins S. Sperm histone H3 lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction. Molecular Metabolism. 2022; 59: 101463.

[Google Scholar]

Tahiri I, Llana SR, Fos-Domènech J, Milà-Guash M, Toledo M, Haddad-Tóvolli R, et al. Paternal obesity induces changes in sperm chromatin accessibility and has a mild effect on offspring metabolic health. Heliyon. 2024; 10: e34043.

[Google Scholar]

Shi Y, Li W, Yu X, Zhao Y, Zhu D, Song Y, et al. Paternal obesity-induced H3K27me3 elevation leads to MANF-mediated transgenerational metabolic dysfunction in female offspring. Advanced Science. 2025; 12: e2415956.

[Google Scholar]

Siklenka K, Erkek S, Godmann M, Lambrot R, McGraw S, Lafleur C, et al. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science. 2015; 350: aab2006.

[Google Scholar]

Mossetti L, Hervás-Herrero I, Gil-Juliá M, Navarro Gomez-Lechon A, Pacheco-Rendón RM, Rivera-Egea R, et al. Effect of paternal body mass index on cumulative live birth rates: retrospective analysis of 3048 embryo transfers in couples using autologous gametes. Cells. 2024; 13: 1836.

[Google Scholar]

Bibi R, Jahan S, Afsar T, Almajwal A, Hammadeh ME, Alruwaili NW, et al. The influence of paternal overweight on sperm chromatin integrity, fertilization rate and pregnancy outcome among males attending fertility clinic for IVF/ICSI treatment. BMC Pregnancy and Childbirth. 2022; 22: 620.

[Google Scholar]

Lingvay I, Cohen RV, Roux CWL, Sumithran P. Obesity in adults. The Lancet. 2024; 404: 972–987.

[Google Scholar]

Tanasescu MD, Rosu AM, Minca A, Rosu AL, Grigorie MM, Timofte D, et al. Beyond BMI: rethinking obesity metrics and cardiovascular risk in the era of precision medicine. Diagnostics. 2025; 15: 3025.

[Google Scholar]

Ashtary-Larky D, Daneghian S, Alipour M, Rafiei H, Ghanavati M, Mohammadpour R, et al. Waist circumference to height ratio: better correlation with fat mass than other anthropometric indices during dietary weight loss in different rates. International Journal of Endocrinology and Metabolism. 2018; 16: e55023.

[Google Scholar]

Browning LM, Hsieh SD, Ashwell M. A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value. Nutrition Research Reviews. 2010; 23: 247–269.

[Google Scholar]

Bray GA. Beyond BMI. Nutrients. 2023; 15: 2254.

[Google Scholar]

Andersen E, Juhl CR, Kjøller ET, Lundgren JR, Janus C, Dehestani Y, et al. Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomized controlled trial. Human Reproduction. 2022; 37: 1414–1422.

[Google Scholar]

Sweatt K, Garvey WT, Martins C. Strengths and limitations of BMI in the diagnosis of obesity: what is the path forward? Current Obesity Reports. 2024; 13: 584–595.

[Google Scholar]

Yamashita K, Kondo T, Osugi S, Shimokata K, Maeda K, Okumura N, et al. The significance of measuring body fat percentage determined by bioelectrical impedance analysis for detecting subjects with cardiovascular disease risk factors. Circulation Journal. 2012; 76: 2435–2442.

[Google Scholar]

Mocini E, Cammarota C, Frigerio F, Muzzioli L, Piciocchi C, Lacalaprice D, et al. Digital anthropometry: a systematic review on precision, reliability and accuracy of most popular existing technologies. Nutrients. 2023; 15: 302.

[Google Scholar]

Zhou XD, Chen QF, Yang W, Zuluaga M, Targher G, Byrne CD, et al. Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021. eClinicalMedicine. 2024; 76: 102848. Erratum in: eClinicalMedicine. 2024; 78: 102958.

[Google Scholar]

Graziani A, Scafa R, Grande G, Ferlin A. Diabetes and male fertility disorders. Molecular Aspects of Medicine. 2024; 99: 101303.

[Google Scholar]

Smith PA, Sarris I, Clark K, Wiles K, Bramham K. Kidney disease and reproductive health. Nature Reviews Nephrology. 2025; 21: 127–143.

[Google Scholar]

Rosman L, Cahill JM, McCammon SL, Sears SF. Sexual health concerns in patients with cardiovascular disease. Circulation. 2014; 129: e313–e316.

[Google Scholar]

GBD 2021 Risk Factors Collaborators. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. 2024; 403: 2162–2203.

[Google Scholar]

Xie F, Xiong F, Yang B, Yan Z, Shen Y, Qin H, et al. Global, regional, and national burden of mortality and DALYs attributable to high body mass index from 1990 to 2021 with projections to 2036. BMC Public Health. 2025; 25: 2053.

[Google Scholar]

Barbouni K, Jotautis V, Metallinou D, Diamanti A, Orovou E, Liepinaitienė A, et al. When weight matters: how obesity impacts reproductive health and pregnancy—a systematic review. Current Obesity Reports. 2025; 14: 37.

[Google Scholar]

George BT, Jhancy M, Dube R, Kar SS, Annamma LM. The molecular basis of male infertility in obesity: a literature review. International Journal of Molecular Sciences. 2023; 25: 179.

[Google Scholar]

Zorena K, Jachimowicz-Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and obesity. Potential link to metabolic disorders and chronic complications. International Journal of Molecular Sciences. 2020; 21: 3570.

[Google Scholar]

Thomas S, Kratzsch D, Schaab M, Scholz M, Grunewald S, Thiery J, et al. Seminal plasma adipokine levels are correlated with functional characteristics of spermatozoa. Fertility and Sterility. 2013; 99: 1256–1263.e3.

[Google Scholar]

Fang H, Judd RL. Adiponectin regulation and function. Comprehensive Physiology. 2018; 8: 1031–1063.

[Google Scholar]

Dong Z, Song X, Dong D, Cai Z. Increased serum leptin levels are associated with metabolic syndrome and semen parameters in patients with infertility. Medicine. 2024; 103: e40353.

[Google Scholar]

Rodríguez-Pérez MDC, Kontro TK, Almeida González D, Gómez Álvarez B, Marcelino Rodríguez I, Cabrera de León YA. Irisin is more strongly associated with leisure-time physical activity than resistin and high-density lipoprotein cholesterol are. Journal of Exercise Science and Fitness. 2022; 20: 366–371.

[Google Scholar]

Würfel M, Breitfeld J, Gebhard C, Scholz M, Baber R, Riedel-Heller SG, et al. Interplay between adipose tissue secreted proteins, eating behavior and obesity. European Journal of Nutrition. 2022; 61: 885–899.

[Google Scholar]

Adeyemi TE, Channa ML, Nadar A. Evaluation of maternal high-fat diet and Quercetin-3-O-rutinoside treatment on the reproductive profile of diet naive male offspring. Life Sciences. 2021; 271: 119179.

[Google Scholar]

Chou HH, Teng MS, Hsu LA, Er LK, Wu S, Ko YL. Circulating chemerin level is associated with metabolic, biochemical and haematological parameters—a population-based study. Clinical Endocrinology. 2021; 94: 927–939.

[Google Scholar]

Estienne A, Reverchon M, Partyka A, Bourdon G, Grandhaye J, Barbe A, et al. Chemerin impairs in vitro testosterone production, sperm motility, and fertility in chicken: possible involvement of its receptor CMKLR1. Cells. 2020; 9: 1599.

[Google Scholar]

Bobjer J, Katrinaki M, Dermitzaki E, Margioris AN, Giwercman A, Tsatsanis C. Serum chemerin levels are negatively associated with male fertility and reproductive hormones. Human Reproduction. 2018; 33: 2168–2174.

[Google Scholar]

Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014; 156: 20–44.

[Google Scholar]

Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, et al. Obesity-linked PPARγ S273 phosphorylation promotes insulin resistance through growth differentiation factor 3. Cell Metabolism. 2020; 32: 665–675.e6.

[Google Scholar]

Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. The Journal of Clinical Investigation. 2017; 127: 74–82.

[Google Scholar]

Fan W, Xu Y, Liu Y, Zhang Z, Lu L, Ding Z. Obesity or overweight, a chronic inflammatory status in male reproductive system, leads to mice and human subfertility. Frontiers in Physiology. 2018; 8: 1117.

[Google Scholar]

Mu Y, Yin TL, Zhang Y, Yang J, Wu YT. Diet-induced obesity impairs spermatogenesis: the critical role of NLRP3 in Sertoli cells. Inflammation and Regeneration. 2022; 42: 24.

[Google Scholar]

Wang J, Zhang S, Hu L, Wang Y, Liu K, Le J, et al. Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice. Cell Death & Disease. 2023; 14: 723.

[Google Scholar]

Hsia SM, Chiang YF, Chen HY, Ali M, Wang PS, Wang KL. Effect of high-fructose diet-induced metabolic syndrome on the pituitary-gonadal axis in male rats. Biomedicines. 2022; 10: 3009.

[Google Scholar]

Leisegang K, Bouic PJ, Menkveld R, Henkel RR. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort. Reproductive Biology and Endocrinology. 2014; 12: 34.

[Google Scholar]

Corradi PF, Corradi RB, Greene LW. Physiology of the hypothalamic pituitary gonadal axis in the male. The Urologic Clinics of North America. 2016; 43: 151–162.

[Google Scholar]

De Silva NL, Papanikolaou N, Grossmann M, Antonio L, Quinton R, Anawalt BD, et al. Male hypogonadism: pathogenesis, diagnosis, and management. The Lancet Diabetes & Endocrinology. 2024; 12: 761–774.

[Google Scholar]

Sharma A, Jayasena CN, Dhillo WS. Regulation of the hypothalamic-pituitary-testicular axis: pathophysiology of hypogonadism. Endocrinology and Metabolism Clinics of North America. 2022; 51: 29–45.

[Google Scholar]

Rohayem J, Alexander EC, Heger S, Nordenström A, Howard SR. Mini-puberty, physiological and disordered: consequences, and potential for therapeutic replacement. Endocrine Reviews. 2024; 45: 460–492.

[Google Scholar]

Romejko K, Rymarz A, Sadownik H, Niemczyk S. Testosterone deficiency as one of the major endocrine disorders in chronic kidney disease. Nutrients. 2022; 14: 3438.

[Google Scholar]

Cortes D, Müller J, Skakkebaek NE. Proliferation of Sertoli cells during development of the human testis assessed by stereological methods. International Journal of Andrology. 1987; 10: 589–596.

[Google Scholar]

Abel MH, Baker PJ, Charlton HM, Monteiro A, Verhoeven G, De Gendt K, et al. Spermatogenesis and Sertoli cell activity in mice lacking sertoli cell receptors for follicle-stimulating hormone and androgen. Endocrinology. 2008; 149: 3279–3285.

[Google Scholar]

Bhattacharya I, Basu S, Pradhan BS, Sarkar H, Nagarajan P, Majumdar SS. Testosterone augments FSH signaling by upregulating the expression and activity of FSH-receptor in pubertal primate Sertoli cells. Molecular and Cellular Endocrinology. 2019; 482: 70–80.

[Google Scholar]

Esteves SC, Humaidan P. The role of luteinizing hormone activity in spermatogenesis: from physiology to clinical practice. Reproductive Biology and Endocrinology. 2025; 23: 6.

[Google Scholar]

Wang JM, Li ZF, Yang WX, Tan FQ. Follicle-stimulating hormone signaling in Sertoli cells: a licence to the early stages of spermatogenesis. Reproductive Biology and Endocrinology. 2022; 20: 97.

[Google Scholar]

Ma X, Dong Y, Matzuk MM, Kumar TR. Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101: 17294–17299.

[Google Scholar]

Salas-Huetos A, Maghsoumi-Norouzabad L, James ER, Carrell DT, Aston KI, Jenkins TG, et al. Male adiposity, sperm parameters and reproductive hormones: an updated systematic review and collaborative meta-analysis. Obesity Reviews. 2021; 22: e13082.

[Google Scholar]

Ahmed F, Hetty S, Laterveer R, Surucu EB, Mathioudaki A, Hornbrinck E, et al. Altered expression of aromatase and estrogen receptors in adipose tissue from men with obesity or type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism. 2025; 110: e3410–e3424.

[Google Scholar]

Smith JT, Acohido BV, Clifton DK, Steiner RA. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. Journal of Neuroendocrinology. 2006; 18: 298–303.

[Google Scholar]

Smith JT, Clifton DK, Steiner RA. Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling. Reproduction. 2006; 131: 623–630.

[Google Scholar]

Quennell JH, Howell CS, Roa J, Augustine RA, Grattan DR, Anderson GM. Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice. Endocrinology. 2011; 152: 1541–1550.

[Google Scholar]

Zhai L, Zhao J, Zhu Y, Liu Q, Niu W, Liu C, et al. Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity. Endocrine. 2018; 62: 195–206.

[Google Scholar]

Fernandez CJ, Chacko EC, Pappachan JM. Male obesity-related secondary hypogonadism–pathophysiology, clinical implications and management. European Endocrinology. 2019; 15: 83–90.

[Google Scholar]

Miller C, Madden-Doyle L, Jayasena C, McIlroy M, Sherlock M, O’Reilly MW. Mechanisms in endocrinology: hypogonadism and metabolic health in men-novel insights into pathophysiology. European Journal of Endocrinology. 2024; 191: R1–R17.

[Google Scholar]

Hong CY, Park JH, Ahn RS, Im SY, Choi HS, Soh J, et al. Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha. Molecular and Cellular Biology. 2004; 24: 2593–2604.

[Google Scholar]

Wen JP, Lv WS, Yang J, Nie AF, Cheng XB, Yang Y, et al. Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential. Biochemical and Biophysical Research Communications. 2008; 371: 756–761.

[Google Scholar]

Wen JP, Liu C, Bi WK, Hu YT, Chen Q, Huang H, et al. Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons. The Journal of Endocrinology. 2012; 214: 177–189.

[Google Scholar]

Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena-Sempere M, Dieguez C, et al. Regulation of pituitary cell function by adiponectin. Endocrinology. 2007; 148: 401–410.

[Google Scholar]

Grossmann M, Jayasena CN, Anawalt BD. Approach to the patient: the evaluation and management of men ≥50 years with low serum testosterone concentration. The Journal of Clinical Endocrinology and Metabolism. 2023; 108: e871–e884.

[Google Scholar]

Liu Y, Hu X, Xiong M, Li J, Jiang X, Wan Y, et al. Association of BMI with erectile dysfunction: a cross-sectional study of men from an andrology clinic. Frontiers in Endocrinology. 2023; 14: 1135024.

[Google Scholar]

González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. International Journal of Molecular Sciences. 2023; 24: 9352.

[Google Scholar]

Lee RK, Chughtai B, Te AE, Kaplan SA. Sexual function in men with metabolic syndrome. The Urologic Clinics of North America. 2012; 39: 53–62.

[Google Scholar]

Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020; 8: 970–987.

[Google Scholar]

Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update. 2017; 23: 646–659.

[Google Scholar]

GBD 2015 Obesity Collaborators; Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health effects of overweight and obesity in 195 countries over 25 years. The New England Journal of Medicine. 2017; 377: 13–27.

[Google Scholar]

Cox AR, Masschelin PM, Saha PK, Felix JB, Sharp R, Lian Z, et al. The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice. Cell Metabolism. 2022; 34: 1932–1946.e7.

[Google Scholar]

Leisegang K, Sengupta P, Agarwal A, Henkel R. Obesity and male infertility: mechanisms and management. Andrologia. 2021; 53: e13617.

[Google Scholar]

Craig JR, Jenkins TG, Carrell DT, Hotaling JM. Obesity, male infertility, and the sperm epigenome. Fertility and Sterility. 2017; 107: 848–859.

[Google Scholar]

Bellastella G, Menafra D, Puliani G, Colao A, Savastano S; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) Group. How much does obesity affect the male reproductive function? International Journal of Obesity Supplements. 2019; 9: 50–64.

[Google Scholar]

Cazzaniga W, Candela L, Boeri L, Capogrosso P, Pozzi E, Belladelli F, et al. The impact of metabolically healthy obesity in primary infertile men: results from a cross-sectional study. Andrology. 2020; 8: 1762–1769.

[Google Scholar]

McPherson NO, Tremellen K. Increased BMI ’alone’ does not negatively influence sperm function—a retrospective analysis of men attending fertility treatment with corresponding liver function results. Obesity Research & Clinical Practice. 2020; 14: 164–167.

[Google Scholar]

McPherson NO, Fullston T, Bakos HW, Setchell BP, Lane M. Obese father’s metabolic state, adiposity, and reproductive capacity indicate son’s reproductive health. Fertility and Sterility. 2014; 101: 865–873.

[Google Scholar]

Oshio LT, Andreazzi AE, Lopes JF, Sá JP, Bolotari M, Costa VMG, et al. A paternal hypercaloric diet affects the metabolism and fertility of F1 and F2 Wistar rat generations. Journal of Developmental Origins of Health and Disease. 2020; 11: 653–663.

[Google Scholar]

Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metabolism. 2016; 23: 369–378.

[Google Scholar]

Wang B, Xia L, Zhu D, Zeng H, Wei B, Lu L, et al. Paternal high-fat diet altered sperm 5′tsRNA-Gly-GCC is associated with enhanced gluconeogenesis in the offspring. Frontiers in Molecular Biosciences. 2022; 9: 857875.

[Google Scholar]

Bak ST, Haupt-Jorgensen M, Dudele A, Wegener G, Wang T, Nielsen AL, et al. The anti-inflammatory agent 5-ASA reduces the level of specific tsRNAs in sperm cells of high-fat fed C57BL/6J mouse sires and improves glucose tolerance in female offspring. Journal of Diabetes and Its Complications. 2023; 37: 108563.

[Google Scholar]

Zhang Y, Ren L, Sun X, Zhang Z, Liu J, Xin Y, et al. Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs. Nature Communications. 2021; 12: 6673.

[Google Scholar]

Akhatova A, Jones C, Coward K, Yeste M. How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health. Clinical Epigenetics. 2025; 17: 7.

[Google Scholar]

Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB Journal. 2013; 27: 4226–4243.

[Google Scholar]

Potabattula R, Dittrich M, Schorsch M, Hahn T, Haaf T, El Hajj N. Male obesity effects on sperm and next-generation cord blood DNA methylation. PLOS ONE. 2019; 14: e0218615.

[Google Scholar]

Keyhan S, Burke E, Schrott R, Huang Z, Grenier C, Price T, et al. Male obesity impacts DNA methylation reprogramming in sperm. Clinical Epigenetics. 2021; 13: 17.

[Google Scholar]

Pantano L, Jodar M, Bak M, Ballescà JL, Tommerup N, Oliva R, et al. The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. RNA. 2015; 21: 1085–1095.

[Google Scholar]

Nätt D, Kugelberg U, Casas E, Nedstrand E, Zalavary S, Henriksson P, et al. Human sperm displays rapid responses to diet. PLOS Biology. 2019; 17: e3000559.

[Google Scholar]

Tomar A, Gomez-Velazquez M, Gerlini R, Comas-Armangué G, Makharadze L, Kolbe T, et al. Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs. Nature. 2024; 630: 720–727.

[Google Scholar]

Pini T, Parks J, Russ J, Dzieciatkowska M, Hansen KC, Schoolcraft WB, et al. Obesity significantly alters the human sperm proteome, with potential implications for fertility. Journal of Assisted Reproduction and Genetics. 2020; 37: 777–787.

[Google Scholar]

Ferigolo PC, Ribeiro de Andrade MB, Camargo M, Carvalho VM, Cardozo KHM, Bertolla RP, et al. Sperm functional aspects and enriched proteomic pathways of seminal plasma of adult men with obesity. Andrology. 2019; 7: 341–349.

[Google Scholar]

Raee P, Shams Mofarahe Z, Nazarian H, Abdollahifar MA, Ghaffari Novin M, Aghamiri S, et al. Male obesity is associated with sperm telomere shortening and aberrant mRNA expression of autophagy-related genes. Basic and Clinical Andrology. 2023; 33: 13.

[Google Scholar]

Liu X, Shi S, Sun J, He Y, Zhang Z, Xing J, et al. The influence of male and female overweight/obesity on IVF outcomes: a cohort study based on registration in Western China. Reproductive Health. 2023; 20: 3.

[Google Scholar]

Zhang X, Wu S, Qi X, Gao S, Qi J, Zhang S, et al. Effect of paternal body mass index on in vitro fertilization and neonatal outcomes among oligozoospermia and asthenospermia patients. World Journal of Men’s Health. 2024; 42: 216–228.

[Google Scholar]

Bian H, Mínguez-Alarcón L, Salas-Huetos A, Bauer D, Williams PL, Souter I, et al.; EARTH Study Team. Male waist circumference in relation to semen quality and partner infertility treatment outcomes among couples undergoing infertility treatment with assisted reproductive technologies. The American Journal of Clinical Nutrition. 2022; 115: 833–842.

[Google Scholar]

Kim J, Patounakis G, Juneau C, Morin S, Neal S, Bergh P, et al. The Appraisal of Body Content (ABC) trial: increased male or female adiposity does not significantly impact in vitro fertilization laboratory or clinical outcomes. Fertility and Sterility. 2021; 116: 444–452.

[Google Scholar]

Mushtaq R, Pundir J, Achilli C, Naji O, Khalaf Y, El-Toukhy T. Effect of male body mass index on assisted reproduction treatment outcome: an updated systematic review and meta-analysis. Reproductive Biomedicine Online. 2018; 36: 459–471.

[Google Scholar]

Santi D, Lotti F, Sparano C, Rastrelli G, Isidori AM, Pivonello R, et al. Does an increase in adipose tissue ’weight’ affect male fertility? A systematic review and meta-analysis based on semen analysis performed using the WHO 2010 criteria. Andrology. 2024; 12: 123–136.

[Google Scholar]

Okechukwu CE. Healthy weight loss maintenance with exercise, liraglutide, or both combined. The New England Journal of Medicine. 2021; 385: 572–573.

[Google Scholar]