Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model
Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6496 |
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| author | Peng Wang Peiqiang Yuan Sen Lin Heju Zhong Xiaoling Zhang Yong Zhuo Jian Li Lianqiang Che Bin Feng Yan Lin Shengyu Xu De Wu Douglas G Burrin Zhengfeng Fang |
| author_facet | Peng Wang Peiqiang Yuan Sen Lin Heju Zhong Xiaoling Zhang Yong Zhuo Jian Li Lianqiang Che Bin Feng Yan Lin Shengyu Xu De Wu Douglas G Burrin Zhengfeng Fang |
| author_sort | Peng Wang |
| collection | DOAJ |
| description | Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s <i>t</i>-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was also carried out using the CORR procedure of SAS to study the relationship between PMSs and BA levels in both maternal and fetal serum at G60, G90, and L0. Allopregnanolone sulphate (PM4S) and epiallopregnanolone sulphate (PM5S) were firstly identified in the maternal and fetal peripheral blood of pregnant sows by using newly developed ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Correlation analysis showed that pregnancy-associated maternal BA homeostasis was correlated with maternal serum PM4S levels, whereas fetal BA homeostasis was correlated with fetal serum PM5S levels. The antagonist activity role of PM5S on farnesoid X receptor (FXR)-mediated BA homeostasis and fibroblast growth factor 19 (FGF19) were confirmed in the PM5S and FXR activator co-treated pig primary hepatocytes model, and the antagonist role of PM4S on FXR-mediated BA homeostasis and FGF19 were also identified in the PM4S-treated pig primary hepatocytes model. Together with the high relative expression of <i>FGF19</i> in pig hepatocytes, the pregnant sow is a promising animal model to investigate the pathogenesis of cholestasis during pregnancy. |
| first_indexed | 2024-03-09T23:34:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:34:49Z |
| publishDate | 2022-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2583ab07aee74cf780b46430f763f3252023-11-23T17:01:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312649610.3390/ijms23126496Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow ModelPeng Wang0Peiqiang Yuan1Sen Lin2Heju Zhong3Xiaoling Zhang4Yong Zhuo5Jian Li6Lianqiang Che7Bin Feng8Yan Lin9Shengyu Xu10De Wu11Douglas G Burrin12Zhengfeng Fang13Key Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaSericultural & Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510000, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaUSDA/ARS Children’s Nutrition Research Center, Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USAKey Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaAbnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s <i>t</i>-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was also carried out using the CORR procedure of SAS to study the relationship between PMSs and BA levels in both maternal and fetal serum at G60, G90, and L0. Allopregnanolone sulphate (PM4S) and epiallopregnanolone sulphate (PM5S) were firstly identified in the maternal and fetal peripheral blood of pregnant sows by using newly developed ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Correlation analysis showed that pregnancy-associated maternal BA homeostasis was correlated with maternal serum PM4S levels, whereas fetal BA homeostasis was correlated with fetal serum PM5S levels. The antagonist activity role of PM5S on farnesoid X receptor (FXR)-mediated BA homeostasis and fibroblast growth factor 19 (FGF19) were confirmed in the PM5S and FXR activator co-treated pig primary hepatocytes model, and the antagonist role of PM4S on FXR-mediated BA homeostasis and FGF19 were also identified in the PM4S-treated pig primary hepatocytes model. Together with the high relative expression of <i>FGF19</i> in pig hepatocytes, the pregnant sow is a promising animal model to investigate the pathogenesis of cholestasis during pregnancy.https://www.mdpi.com/1422-0067/23/12/6496bile acid homeostasispregnancysulfated progesterone metabolitesFXRsows |
| spellingShingle | Peng Wang Peiqiang Yuan Sen Lin Heju Zhong Xiaoling Zhang Yong Zhuo Jian Li Lianqiang Che Bin Feng Yan Lin Shengyu Xu De Wu Douglas G Burrin Zhengfeng Fang Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model International Journal of Molecular Sciences bile acid homeostasis pregnancy sulfated progesterone metabolites FXR sows |
| title | Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model |
| title_full | Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model |
| title_fullStr | Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model |
| title_full_unstemmed | Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model |
| title_short | Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model |
| title_sort | maternal and fetal bile acid homeostasis regulated by sulfated progesterone metabolites through fxr signaling pathway in a pregnant sow model |
| topic | bile acid homeostasis pregnancy sulfated progesterone metabolites FXR sows |
| url | https://www.mdpi.com/1422-0067/23/12/6496 |
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