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The Interaction of PPARα and CYP7B1 with ERα, β Impacted the Occurrence and Development of Intrahepatic Cholestasis in Pregnant Rats

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Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a disorder of bile acid (BA) synthesis, excretion, and metabolism, with systemic accumulation of BAs, which can lead to prematurity, fetal distress, and intrauterine death. Here, we investigate the expression of peroxisome proliferator-activated receptor alpha and cytochrome P450 oxysterol 7alpha-hydroxylase by exposing to 17α-ethynylestradiol with or without the estrogen receptor signaling pathway in pregnant rats with intrahepatic cholestasis. In vivo and in vitro evidences showed that estrogen receptor alpha (ERα) may be the key point of occurrence and development of intra-hepatic cholestasis in pregnant rats. Besides, the abnormalities in genes could be reversed by ERα small interfering RNA. Our findings provide the ERα-centered hypothesis on the mechanisms of ICP. New perspectives are emerging for the treatment of estrogen-induced hepatic complication.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Ninth School of Clinical Medicine, Peking University, Beijing, China

    Zhaoyi Song MD

  2. Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, 100038, China

    Qingyun Shi MD, PhD

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Correspondence to Qingyun Shi MD, PhD.

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Song, Z., Shi, Q. The Interaction of PPARα and CYP7B1 with ERα, β Impacted the Occurrence and Development of Intrahepatic Cholestasis in Pregnant Rats. Reprod. Sci. 24, 627–634 (2017). https://doi.org/10.1177/1933719116667223

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