Melatonin Improves Lactational Bisphenol S Induced Pre-Pubertal and Pubertal Testicular Impairments in Offspring

Abstract

Lactational period is of extreme importance for nourishing and fostering growth in neonates. Bisphenol S (BPS) a congener of bisphenol A (BPA) is an emerging environmental toxicant reported to have deleterious effects on reproductive health. Indirect exposure of BPS to the suckling infants via breastmilk is less explored although it can lead to various public health issues. Therefore, we investigated harmful effects of lactational BPS exposure on pre-pubertal and pubertal testicular functions of the offspring and its possible amelioration by melatonin. Lactating dams were divided into 4 groups: control, melatonin treated (3 mg/kg BW), BPS treated (150 mg/kg BW) and BPS + melatonin co-treatment; the male offspring were evaluated at pre-pubertal (PND 22) and pubertal (PND 42) testicular developmental stages. Lactational BPS exposure affected testicular physiology, led to histological abnormalities, hormonal imbalance, alters blood-testis-barrier (E-cadherin/connexin-43), redox modulators (SIRT-1/FOXO-1/PGC-1α; Nrf2/HO-1/pSTAT-3) and germ cell dynamicity (PCNA/TUNEL positive cells) in both pre-pubertal and pubertal mice. However, melatonin supplementation to BPS exposed lactating mothers improved testicular histoarchitecture in offspring, enhanced testicular antioxidant status, modulated expression of redox/survival and BTB markers that promoted germ cell proliferation. In conclusion, our study shows that lactational BPS exposure could be deleterious to testicular physiology that may result in male infertility/subfertility in later life while melatonin supplementation improves the reproductive health compromised by lactational BPS exposure. © The Author(s), under exclusive licence to Society for Reproductive Investigation 2025.