The Dual Burden of Obesity and Infertility: The Role of Environmental Obesogens in Adipogenesis, Hypogonadism, and Sperm DNA Fragmentation

Abstract

The increasing rates of obesity and male infertility pose major public health challenges, with increasing evidence pointing to environmental obesogens—endocrine-disrupting chemicals (EDCs) that stimulate fat cell development and impaired metabolic function. This review consolidates the extant information on the mechanistic relationship between environmental obesogens and male infertility, highlighting the double role played by obesogens in inducing obesity and compromising reproductive health. Obesogens, a family of environmental chemicals such as bisphenol-A (BPA), phthalates, pesticides, and perfluorinated compounds, compromise the body's fat handling and contribute to male infertility via several inter-related mechanisms. Permanently activating peroxisome proliferator-activated receptor gamma (PPARγ), obesogens increase the development of fat cells and fat storage, upsetting the lipid balance. Concurrently, obesogens compromise the hypothalamic-pituitary-gonadal (HPG) axis, resulting in hypogonadotropic hypogonadism through disrupting hormone signal pathways via estrogenic or anti-androgenic pathways, leptin resistance, and alteration of kisspeptin signaling. The obesity further enhances these by boosting aromatase, converting testosterone to estrogen, which inhibits sperm production and quality, and reducing sex hormone-binding globulin (SHBG) levels, both of which inhibit sperm generation and quality. Moreover, obesogens cause direct testicular damage via oxidative stress, impaired mitochondria, and developmentally induced cell death (apoptosis) of Sertoli and Leydig cells, ultimately compromising blood testis barrier and germ cell survival. Population and laboratory data support the relationship between exposure to obesogens and adverse sperm features, such as diminished sperm movement and concentration, as well as enhanced sperm damage to DNA. Compounding these conditions, the thermal stress and chronic inflammation related to obesity further exacerbate testicular function. This review reflects the multifaceted ways in which environmental obesogens drive male infertility, the importance of minimizing exposure and a series of targeted policies to tackle these related health issues.