Obesity and male infertility: multifaceted reproductive disruption

Abstract

Background: The global prevalence of obesity has soared to a concerning height in the past few decades. Interestingly, the global decline in semen quality is a parallel occurrence that urges researchers to evaluate if obesity is among the most essential causatives of male infertility or subfertility. Main body: Obesity may alter the synchronized working of the reproductive-endocrine milieu, mainly the hypothalamic-pituitary-gonadal (HPG) axis along with its crosstalks with other reproductive hormones. Obesity-mediated impairment in semen parameters may include several intermediate factors, which include physical factors, essentially increased scrotal temperature due to heavy adipose tissue deposits, and systemic inflammation and oxidative stress (OS) initiated by various adipose tissue-derived pro-inflammatory mediators. Obesity, via its multifaceted mechanisms, may modulate sperm genetic and epigenetic conformation, which severely disrupt sperm functions. Paternal obesity reportedly has significant adverse effects upon the outcome of assisted reproductive techniques (ARTs) and the overall health of offspring. Given the complexity of the underlying mechanisms and rapid emergence of new evidence-based hypotheses, the concept of obesity-mediated male infertility needs timely updates and pristine understanding. Conclusions: The present review comprehensively explains the possible obesity-mediated mechanisms, especially via physical factors, OS induction, endocrine modulation, immune alterations, and genetic and epigenetic changes, which may culminate in perturbed spermatogenesis, disrupted sperm DNA integrity, compromised sperm functions, and diminished semen quality, leading to impaired male reproductive functions.