Estrogen-Regulated Proline-Rich Acidic Protein 1 in Endometrial Epithelial Cells Affects Embryo Implantation by Regulating Mucin 1 in Mice.

Abstract

This study explores the regulatory role of proline-rich acidic protein 1 (<i>Prap1</i>) effects on embryo implantation. A high estrogen model and ovariectomized mice were employed to demonstrate that estrogen regulates <i>Prap1</i> expression. Uterine tissues were collected from E 1.5 (the presence of a vaginal plug was recorded as embryonal day 0.5, E 0.5) to E 7.5 to detect the <i>Prap1</i> expression pattern in early pregnancy using qRT-PCR. Embryo adhesion was assessed through uterine perfusion of PRAP1 protein and <i>Prap1</i> overexpression in endometrial epithelial cells (EECs). The data showed that <i>Prap1</i> expression was increased in the uterus with high estrogen levels. <i>Prap1</i> expression was specifically reduced during early implantation. Overexpression of <i>Prap1</i> in EECs also reduced the embryo adhesions. The differentially expressed genes obtained by RNA-seq were enriched in extracellular matrix and cell adhesion. <i>Muc1</i> expression was increased in EECs overexpressing <i>Prap1</i> by RNA-seq and qRT-PCR. Similarly, O-glycosylation biosynthesis was enriched, and glycosylation-related genes were upregulated. Our results demonstrate that <i>Prap1</i> was regulated by estrogen and an increase in PRAP1 before implantation affected embryo adhesion by regulating the expression of <i>Muc1</i> and extracellular matrix-related genes, leading to embryo implantation failure. Our results provide a new insight into estrogen regulation of embryo implantation.