Hippo Signaling in the Endometrium

Abstract

The uterus is essential for embryo implantation and fetal development. During the estrous cycle, the uterine endometrium undergoes dramatic remodeling to prepare for pregnancy. Angiogenesis is an essential biological process in endometrial remodeling. Steroid hormones regulate the series of events that occur during such remodeling. Researchers have investigated the potential factors, including angiofactors, involved in endometrial remodeling. The Hippo signaling pathway discovered in the 21st century, plays important roles in various cellular functions, including cell proliferation and cell death. However, its role in the endometrium remains unclear. In this review, we describe the female reproductive system and its association with the Hippo signaling pathway, as well as novel Hippo pathway genes and potential target genes.

Estrogen Regulates the Expression and Localization of YAP in the Uterus of Mice

“…Orchestrated regulation of uterine endometrium is crucial for successful establishment and maintenance of embryonic implantation and development [ 1 , 2 ]. Embryo implantation is mediated by physical signals between the mother’s uterus and trophoblasts and chemical signals, such as steroid hormones [ 3 ].…”

“…Connective tissue growth factor (CTGF) and cysteine-rich angiogenesis inducer 61 (CYR61) are well-characterized factors that regulate various cellular processes such as proliferation and migration [ 6 , 7 , 8 , 9 ]. YAP is also involved in gene expression of numerous other factors including ADAM metallopeptidase with thrombospondin type 1 motif 1 ( ADAMTS1 ) [ 10 , 11 ], angiomotin ( AMOT ) [ 2 , 12 ], angiomotin like 1 ( AMOTL1 ) [ 13 ], ankyrin repeat domain 1 ( ANKRD1 ) [ 14 , 15 ], catenin alpha 1 ( CTNNA1 ), MCL1 apoptosis regulator, BCL2 family member ( MCL1 ) [ 16 ], amphiregulin ( AREG ), and AXL receptor tyrosine kinase ( AXL ) [ 17 ].…”

“…Recent studies have reported that the Hippo signaling pathway is regulated in reproductive system including the uterus [ 2 ]. We also reported that STK3/4 is regulated by estrogen and its receptor in the endometrium during the estrous cycle.…”

The Development, Differentiation, and Toxicity in Reproduction

“…By looking at the content of reproductive research, it was possible to determine its trends. Among the selected papers, about half were related to male reproduction, e.g., testis and sperm, [1][2][3][4][5][6][7][8][9][10][11][12], and the other half were associated with female reproduction, e.g., oocytes, as well as embryos and their implantation, including three reviews [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

“…Additionally, their regulation involves several cellular signaling pathway along with these hormonal signaling pathways. Recently, several researchers, including us, have been studying the role of hippo signaling in the uterus [21]. In this review, we describe the relationship between hormonal regulation and the hippo signaling pathway as well as a novel regulatory mechanism in the expression of target genes in the uterine endometrium.…”