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

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2024-12-12 DOI:10.1002/bdr2.2423

Jianqiu Han, Zhikai Lu, Yalei Qi, Tengfei Liu, Yongmei Li, Honghui Han, Chen Zhao, Xueyun Ma

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Abstract

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.

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褪黑素通过抗氧化、抗衰老和抗炎途径减弱pfos引起的妊娠小鼠胎盘损伤的生殖毒性。

背景：全氟辛烷磺酸（PFOS）是一种工业合成的持久性有机污染物（POP），与人类生产和日常生活有着错综复杂的关系。已经发现全氟辛烷磺酸与胎儿出生缺陷发生率升高有关。相反，褪黑激素（MLT），一种由松果体分泌的激素，已被证明对生殖发育有保护作用。方法：对暴露于全氟辛烷磺酸（PFOS）的妊娠小鼠同时口服MLT，观察MLT对PFOS诱导的生殖毒性的保护作用。通过监测妊娠结局、胎盘组织学变化、胎盘海绵滋养细胞凋亡和增殖情况，以及抗氧化酶基因、抗衰老基因、抗炎基因等相关基因的表达来评价治疗效果。结果：研究结果表明，MLT治疗逆转了有毒全氟辛烷磺酸引起的不良妊娠结局，包括植入胎儿数量少、新生儿胎儿体重低、再吸收胎儿数量增加。MLT处理降低了妊娠小鼠胎盘中PFOS氧化产物丙二醛（MDA）的水平，并增加了抗氧化酶SOD的水平。此外，MLT还能通过上调抗氧化基因（Nrf2、CAT）和抗衰老基因（Klotho）、抗炎基因（Hsd11b2）的表达，维持胎盘结构的正常化，减少细胞凋亡，维持胎盘海绵滋养细胞的增殖，从而抵消胎盘中PFOS引起的氧化应激，同时还能降低胎盘中炎症基因（Pycard）的表达。结论：本研究结果明确了MLT在减轻受污染的全氟辛烷磺酸对妊娠期生殖发育的有害影响方面的有效性。这为解决全氟辛烷磺酸引起的胎儿出生缺陷提供了一种新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.