Regulation and Function of Laminin A5 during Mouse and Human Decidualization.

Zhen-Shan Yang,Si-Ting Chen,Zeng-Ming Yang,Ying Wang,Hai-Yang Pan,Meng-Yuan Li,Wen-Wen Shi,Ai-Xia Liu,Hai-Yi Zhang,Chen Yang

doi:10.3390/ijms23010199

Abstract

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.

Highlights

Embryo implantation and decidualization are crucial processes for pregnancy establishment in primates and rodents and coordinated by ovarian hormones, growth factors, cytokines, and transcription factors [1]
We found that laminin A5, B2, and C1 are strongly expressed in mouse decidua
Inin A5 siRNA under in vitro decidualization (Figure 3D,E). These results suggested that laminin A5 might play a key role during mouse decidualization

Summary

Introduction

Embryo implantation and decidualization are crucial processes for pregnancy establishment in primates and rodents and coordinated by ovarian hormones, growth factors, cytokines, and transcription factors [1]. The decidual tissue promotes uterine remodeling and maternal vasculature development, which are vital for embryonic survival and growth [3,4]. The major constituents of BMs are fibrous-forming proteins, such as laminin, collagen IV, nidogen, and heparan-sulphate proteoglycans [10,11,12,13]. Agrin, collagen XVIII, and SPARC [14,15,16,17]. BMs regulate uterine differentiation during embryo implantation [19,20,21,22]

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Results

Conclusion