Melatonin Attenuates PFOS-Induced Reproductive Toxicity of Pregnant Mice due to Placental Damage Via Antioxidant, Anti-Aging and Anti-Inflammatory Pathways.

BACKGROUND

Perfluorooctane sulfonate (PFOS), an industrially synthesized persistent organic pollutant (POP), is intricately intertwined with human production and daily life. It has been discovered that PFOS is related to an elevated incidence of birth defects in fetuses. In contrast, melatonin (MLT), a hormone secreted by the pineal gland, has been demonstrated to exert a protective effect on reproductive development.

METHODS

This paper investigates the protective effect of MLT against PFOS-induced reproductive toxicity by simultaneously orally administering MLT to pregnant mice exposed to PFOS. The therapeutic effect was evaluated through the monitoring of pregnancy outcomes, histological changes in the placenta, apoptosis and proliferation of placental spongiotrophoblast, as well as the expression of antioxidant enzyme genes, anti-aging genes, anti-inflammatory genes and other relevant genes.

RESULTS

The results of the study demonstrated that MLT treatment reversed the adverse pregnancy outcomes caused by toxic PFOS, including a low number of implanted fetuses, low neonatal fetal weight, and an increased number of resorbed fetuses. MLT treatment decreased the levels of MDA, an oxidation product generated by PFOS in the placenta of pregnant mice, and increased the levels of the antioxidant enzyme SOD. Additionally, MLT was able to maintain the normalization of placental structure, reduce apoptosis and sustain the proliferation of placental spongiotrophoblast by upregulating the expression of antioxidant genes (Nrf2, CAT) and anti-aging gene (Klotho), anti-inflammatory gene (Hsd11b2), thereby counteracting the oxidative stress caused by PFOS in the placenta, moreover, it also reduced the expression of inflammatory genes (Pycard) in the placenta.

CONCLUSIONS

The findings firmly establish the effectiveness of MLT in mitigating the harmful impacts of tainted PFOS on reproductive development during pregnancy. This provides a novel therapeutic approach for addressing PFOS-induced birth defects in fetuses.