Expression of NFIL3 and CEBPA regulated by IFNT induced-PGE2 in bovine endometrial stromal cells during the pre-implantation period

Rulan Bai; Kazuya Kusama; Yuta Matsuno; Hanako Bai; Toshihiro Sakurai; Koji Kimura; Kazuhiko Imakawa

doi:10.3389/fendo.2023.1075030

Expression of NFIL3 and CEBPA regulated by IFNT induced-PGE2 in bovine endometrial stromal cells during the pre-implantation period

Front Endocrinol (Lausanne). 2023 Feb 21:14:1075030. doi: 10.3389/fendo.2023.1075030. eCollection 2023.

Authors

Rulan Bai¹, Kazuya Kusama², Yuta Matsuno³, Hanako Bai⁴, Toshihiro Sakurai⁵, Koji Kimura⁶, Kazuhiko Imakawa⁷

Affiliations

¹ National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing, China.
² Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
³ Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, United States.
⁴ Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture, Hokkaido University, Hokkaido, Japan.
⁵ School of Pharmaceutical Science, Ohu University, Fukushima, Japan.
⁶ Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan.
⁷ Research Institute of Agriculture, Tokai University, Kumamoto, Japan.

Abstract

Prostaglandin E2 (PGE2) is considered as a luteoprotective factor, influencing the corpus luteum during the early pregnant period in the bovine species. Cyclic AMP (cAMP) is activated in response to PGE2 and plays a role in many physiological processes. The maternal recognition signal, interferon τ (IFNT), induces PGE2 secretion from the endometrial epithelial cells, the function of which in stroma cells has not been completely understood. In this study, PGE2 was found to activate cAMP in the bovine endometrial stromal cells (STRs). STRs were then treated with forskolin to activate the cAMP signaling, from which RNA extracted was subjected to global expression analysis. Transcripts related to transcription regulatory region nucleic acid binding of molecular function, nucleus of cellular component, and mitotic spindle organization of biological processes were up-regulated in cAMP-activated bovine STRs. An increase in the transcription factors, NFIL3, CEBPA, and HIF1A via the cAMP/PKA/CREB signaling pathway in the bovine STRs was also found by qPCR. Knockdown of NFIL3, CEBPA, or HIF1A blocked forskolin-induced PTGS1/2 and IGFBP1/3 expression. Moreover, NFIL3 and CEBPA were localized in endometrial stroma on pregnant day 17 (day 0 = estrous cycle), but not on cyclic day 17. These observations indicated that uterine PGE2 induced by conceptus IFNT is involved in the early pregnancy-related gene expression in endometrial stromal cells, which could facilitate pregnancy establishment in the bovine.

Keywords: bovine; cyclic AMP; endometrium; prostaglandin E2; stomal cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cattle
Colforsin / metabolism
Colforsin / pharmacology
Dinoprostone* / metabolism
Epithelial Cells / metabolism
Female
Pregnancy
Stromal Cells* / metabolism

Substances

Dinoprostone
interferon tau
Colforsin

Grants and funding

This work was supported by JSPS KAKENHI Grant Numbers JP20H03133 (KK) and JP22H02502 (TS), National Natural Science Foundation of China Grant Numbers 32102625 (RB), and CAU-Grant for the Prevention and Control of Immunosuppressive Diseases in Animals (RB).