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  3. Obeticholic acid alleviates intrauterine growth restriction induced by di-ethyl-hexyl phthalate in pregnant female mice by improving bile acid disorder

Obeticholic acid alleviates intrauterine growth restriction induced by di-ethyl-hexyl phthalate in pregnant female mice by improving bile acid disorder

  • Environ Sci Pollut Res Int. 2023 Oct 6. doi: 10.1007/s11356-023-30149-9.
Fan Zhao # 1 2,  Lun Zhang # 1 2,  Mingchao Qu 1 2 3,  Lu Ye 3,  Jiayi Zhang 3,  Yun Yu 1 2,  Qianqian Huang 1 2,  Cheng Zhang 4 5 6,  Jianqing Wang 7 8 9
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, China.
  • 2 Anhui Public Health Clinical Center, Hefei, 230012, China.
  • 3 School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
  • 4 Department of Toxicology, Anhui Medical University, Hefei, China.
  • 5 Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China.
  • 6 MOE Key Laboratory of Population Health Across Life Cycle, Hefei, China.
  • 7 The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, China. jianqingwang81@126.com.
  • 8 Anhui Public Health Clinical Center, Hefei, 230012, China. jianqingwang81@126.com.
  • 9 School of Pharmacy, Anhui Medical University, Hefei, 230032, China. jianqingwang81@126.com.
  • # Contributed equally.
PMID: 37798517 DOI: 10.1007/s11356-023-30149-9
Abstract

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. Intrahepatic cholestasis of pregnancy (ICP), distinguished by maternal pruritus and elevated serum bile acid levels, is linked to unfavorable pregnancy consequences. Few studies have investigated the potential effect of gestational DEHP exposure on the cholestasis in pregnant female mice, and the underlying mechanisms remain unclear. In the present study, a mouse model of cholestasis during pregnancy was established by DEHP exposure. We found that DEHP induces elevated bile acid levels by affecting bile acid synthesis and transporter receptor expression in the maternal liver and placenta of pregnant female mice, ultimately leading to intrauterine growth restriction (IUGR). In addition, DEHP changed the bile acid composition of maternal serum and liver as well as placenta and amniotic fluid in pregnant female mice; Importantly, we found that DEHP down-regulates the expression of farnesoid X receptor (FXR), which is considered to be a bile acid receptor. FXR Agonist obeticholic acid (OCA) effectively alleviated the adverse effects of DEHP on pregnant female mice. While, OCA itself had no adverse effects on normal pregnant female mice. In summary, DEHP could induces bile acid disorder and IUGR in pregnant female mice by affect FXR, which was reversed by OCA.

Keywords

Bile acid; Di-ethyl-hexyl phthalate; Farnesoid X receptor; Intrahepatic cholestasis of pregnancy; Intrauterine growth restriction; Obeticholic acid.

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