IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Impact of human-relevant doses of endocrine-disrupting chemical and drug mixtures on testis development and function

Abstract

In brief: Toxicological studies better resembling human exposures are needed to improve risk assessment. This review presents studies examining the impact of low-dose exposure to endocrine-disrupting chemical (EDC) mixtures, some combined with pharmaceuticals, on male reproduction in animal models and humans.

Abstract: Exposure to EDCs and pharmaceuticals during development has been linked to reproductive dysfunction, reduced semen quality, and infertility. Research indicates that EDC mixtures, which are common in the modern environment, can pose significant risks that may not be fully assessed by studying individual compound toxicity, especially at environmentally relevant doses or concentrations. Understanding the contribution of chemical mixtures to male reproductive toxicity is crucial, given the increasing reliance on pharmaceuticals and pervasiveness of anthropogenic pollution. Recent studies on EDC effects have expanded to a more diverse range of microplastics, pesticides, antimicrobials, phytoestrogens, and pharmaceuticals, such as analgesics, which can collectively impact testicular function and fertility. Adverse outcomes observed across studies include reproductive tract malformations, decreased sperm count and motility, lowered testosterone, delayed-onset puberty, and possible causal effects, such as oxidative stress and altered gene expression. Still, limited data exist on combinations of environmental pollutants and pharmaceuticals with ED potential at human-relevant doses. This review of the recent literature aims to synthesize the toxicological impact of low-dose chemical mixtures on male reproductive health. Overall, humans are exposed to EDCs and drugs through various ways, necessitating an understanding of their concomitant effects on male reproductive health.

Keywords: EDCs and pharmaceutical; environmental effects; low doses; male reproduction; mixtures.