Upregulation of hepatic nuclear receptors in extremely preterm ovine fetuses undergoing artificial placenta therapy.

Autor:	Ikeda H; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia.; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Watanabe S; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Sato S; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Fee EL; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia., Carter SWD; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Kumagai Y; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Takahashi T; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia.; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Kawamura S; Nipro Corporation, Osaka, Japan., Hanita T; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Illanes SE; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Obstetrics and Gynecology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile., Choolani MA; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Saito M; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia.; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Kikuchi A; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan., Kemp MW; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia.; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; School of Veterinary and Life Sciences, Murdoch University, Murdoch, Australia.; Women and Infants Research Foundation, King Edward Memorial Hospital, Subiaco, Australia., Usuda H; Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, Australia.; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
Jazyk:	angličtina
Zdroj:	The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians [J Matern Fetal Neonatal Med] 2024 Dec; Vol. 37 (1), pp. 2301651. Date of Electronic Publication: 2024 Jan 09.
DOI:	10.1080/14767058.2023.2301651
Abstrakt:	Objective: Extremely preterm infants have low Nuclear Receptor (NR) expression in their developing hepatobiliary systems, as they rely on the placenta and maternal liver for compensation. NRs play a crucial role in detoxification and the elimination of both endogenous and xenobiotic substances by regulating key genes encoding specific proteins. In this study, we utilized an Artificial Placenta Therapy (APT) platform to examine the liver tissue expression of NRs of extremely preterm ovine fetuses. This fetal model, resembling a "knockout placenta," lacks placental and maternal support, while maintaining a healthy extrauterine survival. Methods: Six ovine fetuses at 95 ± 1 d gestational age (GA; term = ∼150 d)/∼600 g delivery weight were maintained on an APT platform for a period of 120 h (APT Group). Six age-matched, in utero control fetuses were delivered at 99-100 d GA (Control Group). Fetal liver tissue samples and blood samples were collected at delivery from both groups and assessed mRNA expression of NRs and target transporters involved in the hepatobiliary transport system using quantitative PCR. Data were tested for group differences with ANOVA ( p  < .05 deemed significant). Results: mRNA expression of NRs was identified in both the placenta and the extremely preterm ovine fetal liver. The expression of HNF4α , LRH1 , LXR , ESR1 , PXR , CAR , and PPARα/γ were significantly elevated in the liver of the APT Group compared to the Control Group. Moreover, target transporters NTCP , OATP1B3 , BSEP , and MRP4 were upregulated, whereas MRP2 and MRP3 were unchanged. Although there was no evidence of liver necrosis or apoptotic changes histologically, there was an impact in the fetal liver of the ATP group at the tissue level with a significant increase in TNFα mRNA, a cytokine involved in liver inflammation, and blood elevation of transaminases. Conclusion: A number of NRs in the fetal liver were significantly upregulated after loss of placental-maternal support. However, the expression of target transporter genes appeared to be insufficient to compensate role of the placenta and maternal liver and avoid fetal liver damage, potentially due to insufficient excretion of organic anions.
Databáze:	MEDLINE
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