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The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the GC fate is regulated are unknown in Guanzhong dairy goats. Therefore, we investigated miR-486 expression in small and large follicles, as well as its impact on normal GC survival, apoptosis and autophagy in vitro. Here, we identified and characterized miR-486 interaction with Ser/Arg-rich splicing factor 3 (SRSF3) using luciferase reporter analysis, detecting its role in GC survival, apoptosis and autophagy regulation through qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, mitochondrial membrane potential and monodansylcadaverine, etc. Our findings revealed prominent effects of miR-486 in the regulation of GC survival, apoptosis and autophagy by targeting SRSF3 , which might explain the high differential expression of miR-486 in the ovaries of monotocous dairy goats. In summary, this study aimed to reveal the underlying molecular mechanism of miR-486 regulation on GC function and its effect on ovarian follicle atresia in dairy goats, as well as the functional interpretation of the downstream target gene SRSF3 .

microRNAs (miRNAs) and circular RNAs (circRNAs) are important for endometrial receptivity establishment and embryo implantation in mammals. miR-34a and miR-34c are highly expressed in caprine receptive endometrium (RE). Herein, the functions and mechanisms of miR-34a/c in caprine endometrial epithelial cell (CEEC) apoptosis and RE establishment were investigated. miR-34a/c downregulated the expression level of centrosomal protein 55 (CEP55) and were sponged by circRNA8073 (circ-8073), thereby exhibiting a negative interaction in CEEC. miR-34a/c induced CEEC apoptosis by targeting circ-8073/CEP55 through the regulation of the RAS/RAF/MEK/ERK and phosphoitide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways. Positive and negative feedback loops and cross-talk were documented between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. miR-34a/c regulated the levels of RE marker genes, including forkhead box M1, vascular endothelial growth factor, and osteopontin (OPN). These results suggest that miR-34a/c not only induce CEEC apoptosis by binding to circ-8073 and CEP55 via the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways, but may also regulate RE establishment in dairy goats., (© 2020 Wiley Periodicals LLC.)

The endometrium undergoes a series of complex changes to form a receptive endometrium (RE) that allows the embryo to be implanted. The inability to establish endometrial receptivity of livestock causes embryo implantation failure and considerable losses to animal husbandry. MicroRNAs (miRNAs) are a class of noncoding RNAs. Studies have found that miRNAs can regulate many critical physiological processes, including the establishment of RE during embryo implantation. miR-184 is highly expressed in the endometrial receptive period of dairy goats. This study aimed to explore the effect of miR-184 on endometrial epithelial cell (EEC) apoptosis and RE establishment. Stanniocalcin2 (STC2) is a direct target of miR-184, and miR-184 decreases the expression of STC2 in dairy goat EECs. miR-184 can activate EECs apoptosis through the RAS/RAF/MEK/ERK pathway. Additionally, miR-184 increases the expression levels of RE marker genes, such as forkhead box M1 (FOXM1) and vascular endothelial growth factor (VEGF). These findings indicate that miR-184 promotes the apoptosis of endometrial epithelial cells in dairy goats by downregulating STC2 via the RAS/RAF/MEK/ERK pathway, and that it may also regulate the establishment of RE in dairy goats.

Despite the fact that long noncoding RNAs (lncRNAs) play roles in almost all biological processes, little is known about their biological function in the endometrium during the formation of endometrial receptivity. In this study, a comprehensive analysis of lncRNAs in goat endometrial tissues on Day 5 (prereceptive endometrium, PE) and Day 15 (receptive endometrium, RE) of pregnancy was performed by using RNA-Seq. As a result, 668 differentially expressed lncRNAs (DELs) were found between the PE and RE. Further study showed that lncRNA882, regulated by estrogen (E2) and progestin (P4), could act as competing endogenous RNAs (ceRNAs) for miR-15b, which inhibited the expression of transforming growth factor-b-activated kinase 1 binding protein 3 (TAB3) and then indirectly regulated the level of leukemia inhibitory factor (LIF). This was helpful for the formation of endometrial receptivity in dairy goats. In conclusion, we elucidated the endometrium lncRNA profiles of PE and RE in dairy goats; lncRNA882 acted as a ceRNA for miR-15b and then indirectly regulated the level of LIF in goat endometrial epithelium cells. Thus, this study helped us to better understand the molecular regulation of endometrial receptivity in dairy goats., (© 2018 Wiley Periodicals, Inc.)

Circular RNAs (circRNAs) have been found to play important functional roles in epigenetic regulation under certain physiological and pathological conditions. However, knowledge of circRNAs during the development of receptive endometrium (RE) from pre-RE is limited. In the RE of dairy goats, higher circRNA-9119 levels, with lower miR-26a and higher prostaglandin-endoperoxide synthase 2 (PTGS2) levels, were detected. Further study showed that circRNA-9119 decreased levels of miR-26a by acting as a microRNA sponge, and that miR-26a downregulated the expression of PTGS2 via the predicted target site in endometrial epithelial cells (EECs) of dairy goats in vitro. In this way, circRNA-9119 functioned as a competing endogenous RNAs (ceRNA) that sequestered miR-26a, thereby protecting PTGS2 transcripts from miR-26a-mediated suppression in dairy goat EECs in vitro. Furthermore, PTGS2 participated in the regulation of some protein markers for endometrial receptivity in dairy goat EECs in vitro. Thus, a circRNA-9119-miR-26a-PTGS2 pathway in the endometrium was identified, and modulation of circRNA-9119-miR-26a-PTGS2 expression in EECs may emerge as a potential target to regulate the development of RE.

Circular RNAs (circRNAs) in various tissues and cell types from mammalian sources have been studied. However, present knowledge on circRNAs in the development of pre-receptive endometrium (PE) in dairy goats is limited. In the pre-receptive endometrium of dairy goats, higher circRNA3175 (ciR3175) levels, lower miR-182 levels and higher Testin (TES) levels were detected. And ciR3175 could decreased the miR-182 levels by acting as a miRNA sponge, and miR-182 could down-regulated the expression level of TES via the predicted target site in endometrial epithelial cells (EECs) in vitro. Via this way, ciR3175 functioned as a competing endogenous RNAs (ceRNA) that sequestered miR-182, thereby protecting TES transcripts from miR-182-mediated suppression in EECs in vitro. Further, TES inhibited EECs apoptosis by decreasing the expression level of BCL-2/BAX via the MAPK pathway. Thus, a ciR3175-miR182-TES pathway in the endometrium was identified in EECs, and the modulation of which could emerge as a potential target in regulating the pre-receptive endometrium development in dairy goats., (© 2018 Wiley Periodicals, Inc.)

Circular RNAs (circRNAs) are a large class of endogenous non-coding RNAs that function as regulators in various cells and tissues. Here, the function and mechanism of circRNA8073 (Circ-8073) on endometrial epithelial cells (EECs) and the development of endometrial receptivity were investigated in dairy goats. Circ-8073 could bind to and inhibit miR-449a activity. Circ-8073 binding to the target site of miR-449a had a negative feedback relationship. Centrosomal protein55 (CEP55) was a direct target gene of miR-449a, and Circ-8073 could increase the expression levels of CEP55 by sponging miR-449a in EECs in vitro. Circ-8073/miR-449a/CEP55 could promote EECs proliferation via the PI3K/AKT/mTOR pathway. In addition, CEP55 could regulate the expression levels of vascular endothelial growth factor (VEGF) and forkhead box M1 (FOXM1) in EECs, which contributed to the development of endometrial receptivity. These findings showed that Circ-8073 regulated CEP55 by sponging miR-449a to promote EEC proliferation via the PI3K/AKT/mTOR pathway, suggesting that it could function as a regulator in the development of endometrial receptivity in dairy goats., (Copyright © 2018 Elsevier B.V. All rights reserved.)