Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system.

Obesity and metabolic syndrome (MetS) are global epidemics, driven by an obesogenic environment. This is mediated by complex underlying pathophysiology, in which chronic inflammation is an important aetiological and mechanistic phenomenon. A shift towards a subclinical T_H 1-lymphocyte mediated innate and chronic inflammatory response is well defined in obesity and MetS, demonstrated in multiple systems including visceral adiposity, brain (hypothalamus), muscles, vasculature, liver, pancreas, testes, epididymis, prostate and seminal fluid. Inflammatory cytokines disrupt the hypothalamic-pituitary-testes axis and steroidogenesis cascades (hypogonadotropic hypogonadism), spermatogenesis (poor semen parameters, including DNA fragmentation and detrimental epigenetic modification) and results in subclinical prostatitis and prostate hyperplasia. This review aims to highlight the role of chronic inflammation in obesity and MetS, cytokines in male reproductive physiology and pathophysiology, the impact on steroidogenesis and spermatogenesis, prostate pathology and erectile dysfunction. Currently, it is recommended that clinical assessment of male infertility and reproductive dysfunction in obese and MetS patients includes inflammation assessment (highly sensitive C-reactive protein), and appropriate advice and therapeutic options are incorporated in the management options. However, the mechanisms and therapeutic options remain poorly understood and require significant interdisciplinary research to identify potential novel therapeutic strategies.