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  3. Gestational cadmium exposure disrupts fetal liver development via repressing estrogen biosynthesis in placental trophoblasts

Gestational cadmium exposure disrupts fetal liver development via repressing estrogen biosynthesis in placental trophoblasts

  • Food Chem Toxicol. 2023 Apr 28;113807. doi: 10.1016/j.fct.2023.113807.
Yi-Ting Fu 1,  Jin Zhang 1,  Wei-Bo Liu 1,  Yu-Feng Zhang 1,  Shuang Zhang 1,  Lu-Lu Tan 1,  Qing Lin 1,  Kong-Wen Ou-Yang 1,  Yong-Wei Xiong 1,  Wei Chang 1,  Hao Li 1,  Jun-Ying Yu 2,  Cheng Zhang 3,  De-Xiang Xu 3,  Hua-Long Zhu 4,  Hua Wang 5
Affiliations

Affiliations

  • 1 Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China.
  • 2 Department of Toxicology, School of Public Health, Anhui Medical University, China.
  • 3 Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, China.
  • 4 Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, China. Electronic address: zhuhualongdev@ahmu.edu.cn.
  • 5 Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, China. Electronic address: wanghuadev@ahmu.edu.cn.
PMID: 37121429 DOI: 10.1016/j.fct.2023.113807
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.

Keywords

Cadmium; Fetal liver development; Ovariectomy; Placental estradiol.

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