1. Gestational cadmium exposure disrupts fetal liver development via repressing estrogen biosynthesis in placental trophoblasts.
- Author
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Fu, Yi-Ting, Zhang, Jin, Liu, Wei-Bo, Zhang, Yu-Feng, Zhang, Shuang, Tan, Lu-Lu, Lin, Qing, Ou-Yang, Kong-Wen, Xiong, Yong-Wei, Chang, Wei, Li, Hao, Yu, Jun-Ying, Zhang, Cheng, Xu, De-Xiang, Zhu, Hua-Long, and Wang, Hua
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FETAL development , *TROPHOBLAST , *CADMIUM , *PLACENTA , *ESTROGEN , *BIOSYNTHESIS - Abstract
Cadmium (Cd), commonly found in diet and drinking water, is known to be harmful to the human liver. Nevertheless, the effects and mechanisms of gestational Cd exposure on fetal liver development remain unclear. Here, we reported that gestational Cd (150 mg/L) exposure obviously downregulated the expression of critical proteins including PCNA, Ki67 and VEGF-A in proliferation and angiogenesis in fetal livers, and lowered the estradiol concentration in fetal livers and placentae. Maternal estradiol supplement alleviated aforesaid impairments in fetal livers. Our data showed that the levels of pivotal estrogen synthases, such as CYP17A1 and 17β-HSD, was markedly decreased in Cd-stimulated placentae but not fetal livers. Ground on ovariectomy (OVX), we found that maternal ovarian-derived estradiol had no major effects on Cd-impaired development in fetal liver. In addition, Cd exposure activated placental PERK signaling, and inhibited PERK activity could up-regulated the expressions of CYP17A1 and 17β-HSD in placental trophoblasts. Collectively, gestational Cd exposure inhibited placenta-derived estrogen synthesis via activating PERK signaling, and therefore impaired fetal liver development. This study suggests a protective role for placenta-derived estradiol in fetal liver dysplasia shaped by toxicants, and provides a theoretical basis for toxicants to impede fetal liver development by disrupting the placenta-fetal-liver axis. [Display omitted] • Gestational cadmium exposure impairs fetal liver development. • Estradiol supplement alleviates cadmium-induced fetal liver dysplasia. • Cadmium inhibits fetal liver development partly via reducing placental estradiol. • Cadmium represses placental estradiol synthesis via activating PERK signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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