Melatonin Improves Lactational Bisphenol S Induced Pre-Pubertal and Pubertal Testicular Impairments in Offspring
Aishwarya Sahu1, Vartika Malik1, Rakesh Verma2
1Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, U.P., India.
Insights
Lactational exposure to Bisphenol S (BPS) harms offspring testicular development. Melatonin supplementation during lactation mitigates these harmful effects, improving reproductive health in male mice.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Developmental Toxicology
Background:
- Bisphenol S (BPS) is an emerging environmental toxicant linked to reproductive health issues.
- Infant exposure to BPS via breastmilk during lactation is a significant public health concern.
- The impact of lactational BPS exposure on male offspring's testicular development requires thorough investigation.
Purpose of the Study:
- To investigate the detrimental effects of lactational BPS exposure on pre-pubertal and pubertal testicular functions in male offspring.
- To evaluate the potential protective role of melatonin against BPS-induced testicular toxicity.
- To assess the impact on hormonal balance, blood-testis barrier, redox status, and germ cell dynamics.
Main Methods:
- Lactating dams were divided into control, melatonin, BPS, and BPS+melatonin groups.
- Male offspring were assessed at pre-pubertal (postnatal day 22) and pubertal (postnatal day 42) stages.
- Evaluations included testicular histology, hormone levels, blood-testis barrier markers, redox modulators, and germ cell proliferation/apoptosis markers.
Main Results:
- Lactational BPS exposure induced testicular abnormalities, hormonal imbalance, and altered blood-testis barrier integrity.
- BPS exposure disrupted redox modulators and germ cell dynamics, indicated by altered PCNA and TUNEL positive cells.
- Melatonin co-treatment significantly improved testicular histoarchitecture, antioxidant status, and modulated key molecular markers, promoting germ cell proliferation.
Conclusions:
- Lactational BPS exposure poses a significant risk to testicular physiology, potentially leading to long-term male infertility or subfertility.
- Melatonin supplementation during lactation effectively ameliorates the adverse effects of BPS exposure on offspring testicular development and reproductive health.
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.
