Obesity-Related Impacts on Male Fertility

Obesity is a global health concern with profound repercussions on male reproductive function. Excess adipose tissue alters endocrine homeostasis by increasing aromatisation of androgens to oestrogens, disrupting the hypothalamic–pituitary–gonadal axis and promoting functional hypogonadism. Insulin resistance, chronic low–grade inflammation and oxidative stress compromise Sertoli and Leydig cell activity, leading to impaired spermatogenesis, reduced testosterone synthesis and deranged blood–testis barrier integrity. These changes manifest as declines in sperm concentration, motility, morphology and DNA integrity, with emerging evidence of epigenetic modifications that may affect offspring health. Lifestyle interventions and targeted therapies aim to restore hormonal balance and protect testicular function, underscoring the importance of early detection and personalised management strategies.

Research from Nature Portfolio

Recent studies have elucidated molecular pathways linking metabolic stress to testicular dysfunction. One investigation into Sertoli cell metabolism revealed that obesity during childhood and adolescence perturbs nutrient sensing and mitochondrial activity within the seminiferous epithelium, setting the stage for reduced sperm output in adulthood. Another work examined the role of autophagy in diet‐induced spermatogenic impairment, demonstrating that excessive autophagic activation in germ cells exacerbates apoptotic damage and that pharmacological inhibition of autophagy can rescue sperm production and fertility parameters in animal models. These findings highlight both developmental windows of vulnerability and novel cellular targets for intervention.

Obesity-Related Impacts on Male Fertility publication trend

The graph below shows the total number of articles in obesity-related impacts on male fertility across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: A cellular degradation pathway that recycles damaged organelles and proteins; dysregulation contributes to germ cell loss in obesity.

Functional hypogonadism: Reduced testosterone production without primary testicular failure, often linked to metabolic disorders.

Pyroptosis: A form of programmed cell death associated with inflammation, observed in Leydig cells under metabolic stress.

Adipokines: Bioactive peptides secreted by adipose tissue that modulate inflammation and endocrine function.

Blood–testis barrier: A tight‐junction structure formed by Sertoli cells that protects germ cells; its disruption impairs spermatogenesis.

Insulin resistance: A state in which cells fail to respond adequately to insulin, contributing to hormonal imbalances that affect testicular function.

References

1. Molecular insights into Sertoli cell function: how do metabolic disorders in childhood and adolescence affect spermatogonial fate?. Nature Communications (2024).
2. Diet-induced obesity impairs spermatogenesis: a potential role for autophagy. Scientific Reports (2017).
3. Obesity and male fertility disorders. Molecular Aspects of Medicine (2024).
4. Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice. Cell Death & Disease (2023).
5. Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes. Cells (2024).