Hyperlipidemia negatively impacts implantation by dysregulating tight junction and Claudin-3 and Claudin-4 expression in the endometrium.

Autor: Zhang Y; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Zhang Y; Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China., Xia X; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Gao L; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Gao C; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Zhou J; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Yan Z; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Cui Y; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China., Ma X; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China. Electronic address: sxmaxiang@126.com., Kwak-Kim JYH; Reproductive Medicine and Immunology, Obstetrics and Gynecology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3471 N Green Bay Road, North Chicago, IL 60064, USA. Electronic address: joanne.kwakkim@rosalindfranklin.edu., Diao F; Department of Reproductive Medicine, Jiangsu Province Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China. Electronic address: phenix_y@163.com.
Jazyk: angličtina
Zdroj: Journal of reproductive immunology [J Reprod Immunol] 2024 Dec; Vol. 166, pp. 104326. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.jri.2024.104326
Abstrakt: Clinical observational studies have suggested hyperlipidemia may disturb embryo implantation through endometrium; however, the mechanism has been unclear. With its profound implications for reproductive health, the present study aims to investigate whether hyperlipidemia affects endometrial epithelial cell tight junctions for implantation failures. By constructing hyperlipidemia mice model, the number and distribution of embryo implantation status were investigated after both natural mating and in vitro fertilization and embryo transfer (IVF-ET). Transmission electron microscopy (TEM) was used to compare the ultrastructure of tight junctions in endometrial endothelial cells. Western blot and immunofluorescence were used to explore the expression and localization of tight junction proteins, such as Claudin (CDLN)3, CLDN4, occludin (OCLN), and zonula occludens-1 (ZO1). For women with reproductive failure, mid-luteal phase endometrial tissues were collected, and gene expression of tight junction proteins was investigated using RNA sequencing and qRT-PCR. In hyperlipidemic mice, the number of embryo implantation sites significantly decreased with uneven distribution after natural mating and IVF-ET. Disrupted tight junctions were found, characterized by a decreased number of tight junctions by TEM, downregulated expressions of CDLN4, OCLN, and ZO1, and an increased expression of CLDN3 by western blot. In hyperlipidemic women with reproductive failure, the dysregulated expression of CLDN3 and CLDN4 was also present in the luteal phase endometrium. In this study, evaluation of both animal models and infertile women in vivo demonstrated that hyperlipidemia reduced female fertility, accompanied by disruption of tight junction structures and dysregulation of CLDN3 and CLDN4 expression in the endothelial cells of luteal phase endometrium.
Competing Interests: Declaration of Competing Interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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