Downregulation of PGRMC1 accelerates differentiation and fusion of a human trophoblast cell line

in Journal of Endocrinology
Authors:
Atsuya Tsuru Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Mikihiro Yoshie Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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https://orcid.org/0000-0001-5898-7950
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Mei Suzuki Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Hiroki Mochizuki Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Satoshi Kametaka Division of Biofunctional Sciences, Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Aichi, Japan

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https://orcid.org/0000-0003-0659-6426
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Takako Ohmaru-Nakanishi Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Mana Azumi Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Kazuya Kusama Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Kiyoko Kato Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Kazuhiro Tamura Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

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Correspondence should be addressed to M Yoshie: yoshie@toyaku.ac.jp
DOI:
https://doi.org/10.1530/JOE-23-0163
Volume/Issue:
Volume 260: Issue 2
Article Type:
Research Article
Article ID:
e230163
Online Publication Date:
08 Dec 2023
Copyright:
© the author(s) 2023
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Mononuclear cytotrophoblasts (CTs) differentiate and fuse to form multinuclear syncytiotrophoblasts (STs), which produce human chorionic gonadotropin (hCG) and progesterone to maintain pregnancy. Impaired differentiation and fusion of CTs to form STs are associated with hypertensive disorders of pregnancy and fetal growth restriction. Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional single transmembrane heme-binding protein. We previously demonstrated that downregulation of PGRMC1 promotes endometrial stromal cell differentiation (decidualization). Here, we explored the role of PGRMC1 in trophoblast differentiation and fusion. PGRMC1 expression was lower in STs than in CTs of first-trimester placental tissues. PGRMC1 expression in BeWo cells (a trophoblast-derived choriocarcinoma cell line) decreased upon dibutyryl-cAMP (db-cAMP)-induced differentiation. Both inhibition and knockdown of PGRMC1 stimulated hCG production in the presence of db-cAMP. Furthermore, a quantitative cell fusion assay we developed revealed that inhibition and knockdown of PGRMC1 enhanced db-cAMP-stimulated cell fusion. Peroxisome proliferator-activated receptor γ (PPARγ) agonists decreased PGRMC1 expression and stimulated the cell fusion in BeWo cells. These findings suggest that downregulation of PGRMC1 expression in part through activation of PPARγ during trophoblast differentiation promotes hCG production and cell fusion for formation and maintenance of placental villi during pregnancy.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2023
Article ID:
e230163
Article Type:
Research Article
Received Date:
24 May 2023
Accepted Date:
14 Nov 2023
Print Publication Date:
01 Feb 2024
Online Publication Date:
08 Dec 2023
Keywords:
progesterone receptor membrane component 1 (PGRMC1); trophoblast; differentiation; fusion

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