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褪黑素对铬致孕鼠生殖毒性逆转作用的新认识。

New insights into the reverse of chromium-induced reprotoxicity of pregnant mice by melatonin.

机构信息

College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai 201418, China.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China; Peninsula Cancer Center, Binzhou Medical University, Yantai, Shandong 264003, China.

出版信息

Ecotoxicol Environ Saf. 2022 Jun 15;238:113608. doi: 10.1016/j.ecoenv.2022.113608. Epub 2022 May 4.

Abstract

Hexavalent chromium Cr(VI) is a well-known environmental toxic metal that causes reprotoxicity in pregnant females. There are currently no appropriate interventions or treatments for Cr(VI) exposure during pregnancy. Herein, the protective effect of melatonin (MLT) against Cr(VI)-induced reprotoxicity is investigated by administrating MLT to pregnant mice exposed to Cr(VI). The results indicate that MLT effectively alleviates Cr(VI)-induced adverse pregnancy outcomes, restoring the decreased fetal weight and increased fetal resorption and malformation caused by Cr(VI) exposure to normal levels. MLT reduces the negative effects of Cr(VI) on follicular atresia and the development of primordial follicle in the maternal ovarian, thereby mitigating the decline in the reserve of primordial follicles. MLT alleviates Cr(VI)-induced oxidative stress, hence reducing the excessive accumulation of malondialdehyde in the maternal ovary. MLT inhibits Cr(VI)-induced apoptosis of ovarian granulosa cells and the expression of cleaved caspase-3 in the ovary. MLT reduces the increase in serum follicle-stimulating hormone caused by Cr(VI) exposure, while elevating anti-Mullerian hormone levels. We demonstrate that MLT reverses Cr(VI)-induced reprotoxicity in pregnant mice, opening up a new avenue for treating reproductive defects caused by environmental stress.

摘要

六价铬 Cr(VI) 是一种众所周知的环境毒性金属,会对孕妇造成生殖毒性。目前,针对孕妇 Cr(VI) 暴露,尚无适当的干预或治疗措施。本研究通过给予怀孕小鼠 MLT(褪黑素)来研究 MLT 对 Cr(VI) 诱导的生殖毒性的保护作用。结果表明,MLT 可有效缓解 Cr(VI) 引起的不良妊娠结局,使 Cr(VI) 暴露导致的胎儿体重下降和胎儿吸收率增加及畸形恢复正常水平。MLT 减轻了 Cr(VI) 对卵泡闭锁和母鼠卵巢原始卵泡发育的负面影响,从而减缓了原始卵泡储备的下降。MLT 缓解了 Cr(VI) 引起的氧化应激,从而减少了母鼠卵巢中丙二醛的过度积累。MLT 抑制了 Cr(VI) 诱导的卵巢颗粒细胞凋亡和卵巢中 cleaved caspase-3 的表达。MLT 降低了 Cr(VI) 暴露引起的血清卵泡刺激素水平升高,同时提高了抗苗勒管激素水平。我们的研究表明,MLT 可逆转怀孕小鼠的 Cr(VI) 诱导的生殖毒性,为治疗环境应激引起的生殖缺陷开辟了新途径。

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