Abstract
Increasing evidence has shown that miRNAs play important roles in endometrium development during the menstrual cycle in humans and many other animals. Our previous data indicated that miR-182 levels increase 15.55-fold and pleiotrophin (PTN) levels decrease 20.97-fold in the receptive endometrium (RE, D15) compared with the pre-receptive endometrium (PE, D5) in dairy goats. The present study shows that miR-182 is widely expressed in different tissues of dairy goats and that its expression levels are regulated by E2 and P4 in endometrial epithelium cells (EECs). We confirmed that PTN is a target of miR-182 and that miR-182 regulates the protein levels of AKT, Bcl-2, FAS, MAPK, Caspase-3 and SP1 in EECs. Furthermore, miR-182 up-regulates or maintains the expression levels of osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in EECs, suggesting that miR-182 is an important regulatory factor in the construction of endometrial receptivity in dairy goats. In conclusion, miR-182 participates in the development of endometrial receptivity by down-regulating PTN and affecting the expression of select apoptosis-related genes and increasing or maintaining the expression levels of OPN, COX-2 and PRLR in the EECs of dairy goats.
Highlights
The endometrium is lined by epithelial cells (EEC) and is supported by a stromal cell (ESC) foundation [1]
The present study shows that miR-182 is widely expressed in different tissues in dairy goats, and the levels vary in association with the concentrations of E2 and P4 in EECs
We found that the COX2 protein levels were down-regulated by the miR-182 inhibitors, but the levels changed when the cells were treated with the miR-182 mimics, suggesting that miR-182 may be an essential factor to maintain the expression of COX2 protein levels in dairy goat EECs
Summary
The endometrium is lined by epithelial cells (EEC) and is supported by a stromal cell (ESC) foundation [1]. The EEC layer is essential for reproductive success, including nutrition supply for embryo implantation and pregnancy maintenance [2, 3]. Endometrial receptivity is the result of both the synchronized and integrated interaction among many factors, and the reconstruction of the endometrium that allows for embryo adhesion [4]. Timing of implantation and endometrial receptivity have major impact on the establishment of a successful pregnancy and on the future health of offspring [5]. Many factors participate in the development and progression of endometrial receptivity, the underlying molecular mechanisms are not very clear. A better understanding of the development of endometrial receptivity, reproductive function and fecundity of animals is urgent
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