Obesity, a global health concern defined by excessive adiposity and persistent metabolic imbalance, has far‑reaching implications that extend beyond standard metabolic and cardiovascular comorbidities. While the association between obesity and reproductive dysfunction is well‑established, the precise molecular mechanisms underlying these associations remain incompletely understood, particularly as regards the distinction between obesity‑specific effects and those mediated by dietary components or metabolic syndrome. The present review integrates currently available knowledge on the mechanisms through which obesity impairs reproductive function in both sexes, from gametogenesis to postnatal development. In males, obesity drives testicular inflammation, disrupts spermatogenesis, impairs sperm motility and DNA integrity, and alters key signaling pathways, with oxidative stress and metabolic endotoxemia as central mediators. In females, obesity induces ovarian dysfunction, alters steroidogenesis, compromises oocyte quality and disrupts follicular environments, leading to reduced fertility and adverse pregnancy outcomes. However, the relative contribution of obesity‑induced inflammation vs. direct lipotoxic effects remains poorly characterized in both sexes. The present review further examines the impact of parental obesity on fertilization capacity, placental function and in utero development, highlighting sex‑specific and intergenerational effects mediated by mitochondrial dysfunction and epigenetic modifications. Notably, maternal obesity impairs placental and fetal organ development, increases the risk of metabolic and reproductive disorders in offspring, and alters key developmental signaling pathways. While some studies suggest that lifestyle interventions and antioxidant therapies may partially reverse obesity‑induced reproductive impairments, significant gaps remain in understanding the precise molecular mechanisms and potential for therapeutic rescue. By synthesizing findings from animal models and human studies, the present review highlights the pivotal role of oxidative stress as a mechanistic link between obesity and reproductive dysfunction. It emphasizes the need for further research to inform clinical strategies aimed at mitigating these adverse outcomes.
Pavlović et al. (Wed,) studied this question.