TNFα/TNFR1 signal induces excessive senescence of decidua stromal cells in recurrent pregnancy loss. (February 2023)

• Record Type: Journal Article
• Authors: Zeng, Shanshan; Liang, Yingyu; Lai, Siying; Bi, Shilei; Huang, Lijun; Li, Yulian; Deng, Weinan; Xu, Pei; Liu, Mingxing; Xiong, Zhongtang; Chen, Jingsi; Tu, Zhaowei; Chen, Dunjin; Du, Lili
• Is Part Of: Journal of reproductive immunology. Volume 155(2023)
• Publication Date: 2023-02
• Subjects: RPL recurrent pregnancy loss -- DSCs decidual stromal cells -- ESCs endometrial stromal cells -- PRL prolactin -- IGFBP1 insulin-like growth factor binding protein 1 -- SASP senescence-associated secretory phenotype -- TNFα tumor necrosis factor-α -- P/S penicillin/streptomycin -- CS-FBS charcoal-stripped fetal bovine serum -- MPA medroxyprogesterone 17-acetate -- dbcAMP dibutyryl cAMP -- TMA tissue microarray -- SA-βgal senescence-associated β-galactosidase -- hCG human chorionic gonadotropin -- TNFR1 tumor necrosis factor receptor 1 -- TNF tumor necrosis factor -- VCT villous cytotrophoblasts -- ESHRE European Society of Human Reproduction and Embryology -- ASRM American Society for Reproductive Medicine; Recurrent pregnancy loss -- Decidual stromal cells -- Cellular senescence -- TNFα -- TNFR1; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2022.103776
• Languages: English
• ISSNs: 0165-0378

Abstract

Abstract: Defects in decidual response are associated with adverse pregnancy outcomes which includes recurrent pregnancy loss (RPL). It is reported that cellular senescence happens during decidualization and pro-senescent decidual response in the luteal phase endometrium is related to RPL. However, the underlying mechanisms of how excessive decidual senescence takes place in RPL decidua cells remain largely unexplored. The senescent phenotype of RPL decidua and tumor necrosis factor receptor 1(TNFR1) expression were analyzed by using our previously published single-cell sequencing dataset of decidua cells from 6 RPL and 5 matched normal decidua, which were further verified by PCR and WB in decidual tissues. Effects of TNFα on the decidual stromal cells (DSCs) senescence and underlying molecular pathways were analyzed using the in vitro decidualization model of human endometrial stromal cells (HESCs). We showed that decidual stroma cells from RPL patients exhibited transcriptomic features of cellular senescence by analysis of single-cell datasets. The TNFα level and TNFR1 expression were increased in RPL decidua tissues. Furthermore, in vitro cell model demonstrated that increased TNFα induced excessive senescence during decidualization and TNFR1/p53/p16 pathway mediates TNFα-induced stromal senescence. In addition, we also found that the expression of IGFBP1 was regulated by TNFα-TNFR1 interaction during decidualization. Taken together, the present findings suggest that the increased secretion of TNFα induced stromal cell excessive senescence in RPL decidua, which is mediated via TNFR1, and thus provide a possible therapeutic target for the treatment of RPL. Highlights: Decidual stroma cells from RPL patients exhibited transcriptomic features of cellular senescence. Low-dose TNFα induced excessive senescence in human endometrial stromal cells. TNFR1/P53 pathway mediates TNFα-induced stromal senescence. Increased secretion of TNFα induced stromal cell senescence in RPL decidua, which is mediated via TNFR1.