Roles of WNT6 in Sheep Endometrial Epithelial Cell Cycle Progression and Uterine Glands Organogenesis.

Xiaoxiao Gao,Zifei Liu,Kang Li,Yaxu Liang,Xiaolei Yao,Feng Wang,Yingqi Li,Guomin Zhang,Xiaodan Li,Zhibo Wang

doi:10.3390/vetsci8120316

Abstract

The uterus, as part of the female reproductive tract, is essential for embryo survival and in the maintenance of multiple pregnancies in domestic animals. This study was conducted to investigate the effects of WNT6 on Hu sheep endometrial epithelial cells (EECs) and uterine glands (UGs) in Hu sheep, with high prolificacy rates. In the present study, Hu sheep with different fecundity, over three consecutive pregnancies, were divided into two groups: high prolificacy rate group (HP, litter size = 3) and low prolificacy rate group (LP, litter size = 1). A comparative analysis of the endometrial morphology was performed by immunofluorescence. RNA-seq was used to analyze the gene’s expression in endometrium of HP and LP Hu sheep, providing a candidate gene, which was investigated in EECs and organoid culture. Firstly, higher density of UGs was found in the HP Hu sheep groups (p < 0.05). The RNA-seq data revealed the importance of the WNT signaling pathway and WNT6 gene in Hu sheep endometrium. Functionally, WNT6 could promote the cell cycle progression of EECs via WNT/β-catenin signal and enhance UGs organogenesis. Taken together, WNT6 is a crucial regulator for sheep endometrial development; this finding may offer a new insight into understanding the regulatory mechanism of sheep prolificacy.

Highlights

Hu sheep are considered a prolific breed
The gene expression levels of growth factors related to uterine glands (UGs) development were detected by RT-qPCR, and results showed that the expression levels of HOXA10, HOXA11, FOXA2, PLGF, IGF-1, PGR, VEGFA, and LGR5
In total 874 differentially expressed (DE) mRNAs were identified in endometrium between the HP and LP groups, with 440 upregulated and 434 downregulated DE mRNAs (p < 0.05; Figure 2A)

Summary

Introduction

Hu sheep are considered a prolific breed. As in other prolific breeds, this trait is associated with a particular genetic background (related to the Booroola gene, FecB).Interestingly, some ewes carrying the FecB gene, a marker of a high ovulation rate, still reveal a low prolificacy rate [1]. Hu sheep are considered a prolific breed. As in other prolific breeds, this trait is associated with a particular genetic background (related to the Booroola gene, FecB). Some ewes carrying the FecB gene, a marker of a high ovulation rate, still reveal a low prolificacy rate [1]. Differences in the fecundity of sheep would derive, likely, from non-genetic influences (such as nutrition). Mammalian fecundity is controlled by ovulation rate and uterine receptivity. Uterine development and receptivity are closely related to the prolificacy rate of Hu sheep [2]. Even though many studies have focused on the regulation of ovulation, little research has been conducted on the effects of uterine development on fertility.

Methods

Results

Conclusion