Reproductive toxicity of endosulfan: Mechanisms and impacts on female and male reproductive health

Abstract

Endosulfan is a broad-spectrum organochlorine pesticide widely used in many developing countries despite its high toxicity potential. Endosulfan, listed as potent endocrine-disrupting chemical and xenoestrogen, gains importance for its potential to cause reproductive and developmental dysfunction. In females, endosulfan disrupts ovarian and uterine development, leading to infertility, miscarriage, and developmental toxicity. It acts by mimicking estrogen and interferes with estrogen and androgen pathways, impacting hormone regulation and gene expression, including estrogen receptor α (ERα) and progesterone receptors. Endosulfan triggers oxidative stress in ovaries, reduces follicle count, and impairs uterine differentiation, affecting embryo implantation. Additionally, it alters gene expression and causes epigenetic modifications, contributing to reproductive dysfunctions. In males, endosulfan affects spermatogenesis by causing oxidative stress, mitochondrial dysfunction, and lipid peroxidation. It reduces sperm quality, motility, and quantity, with effects on testicular tissues, sperm chromatin condensation, and enzymatic activity. Oxidative damage, increased reactive oxygen species (ROS), and disrupted energy metabolism are central to its toxicity. Epidemiological studies also link pesticide exposure to reduced sperm counts, higher DNA fragmentation, and infertility. Moreover, endosulfan can cross the placental barrier, leading to fetal resorption, malformations, and maternal toxicity. This review provides a comprehensive overview of the reproductive toxicity of endosulfan in males and females. We also highlight the various possible mechanisms of reproductive toxicity of endosulfan and its potential to impart deleterious effects over HPG axis, gonads, and uterine differentiation and development and implantation.