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Litter size is a critical economic trait in livestock, but only a few studies have focused on associated indel mutations in BMPR1B, a key regulator of ovulation and litter size in sheep. We evaluated the effects of BMPR1B mutations on the reproductive performance of sheep. We used Hu, East Friesian, and East Friesian/Hu crossbred sheep as experimental subjects and identified a novel 90 bp deletion in BMPR1B, which coincides with the c.746A > G (FecB mutation) genotype. The correlation between the two loci and litter size was then evaluated. We identified three genotypes for the Del-90bp locus, namely, II, ID, and DD, and three genotypes for the c.746A > G locus, namely ++, B+, and BB. Both Del-90bp and c.746A > G significantly affected the litter size of Hu and East Friesian/Hu crossbred sheep. Linkage disequilibrium analysis revealed a strong linkage disequilibrium between these loci in Hu sheep and the F1 population (r2 > 0.33), which suggests that detecting this 90 bp deletion might be a simple method to identify the likely carriers of c.746A > G. However, the function of this 90-bp deletion still needs further exploration. We provide genetic data that can be used as a reference for the breeding of improved prolific traits in sheep. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Transcriptomics is an established powerful tool to identify potential mRNAs and ncRNAs (non‐coding RNAs) for endometrial receptivity. In this study, the goat endometrium at estrus day 5 (ED5) and estrus day 15 (ED15) were selected to systematically analyse the differential expressed genes (DEGs) what were induced by the embryo. There were 1,847 genes which were significantly differential expressed in endometrium induced by the embryo at ED5, and 1,346 at ED15 (p‐value <.05). Secreted phosphoprotein 1 (SPP) was the responsive genes for embryo in the goat endometrium during estrus cycle, neurotensis (NTS) and pleiotrophin (PTN) were the responsive genes for embryo in the goat endometrium at ED5, Testin (TES) and Phosphate and Tension Homology Deleted on Chromsome ten (PTEN) at ED15. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis revealed cytoplasm and Endocytosis were indispensable for the endometrium development in dairy goat. In a word, this resulting view of the transcriptome greatly uncovered the global trends in mRNAs expression induced by the embryo in the endometrium of dairy goats. [ABSTRACT FROM AUTHOR]

Cyclic changes in the endometrium are essential for embryo implantation in mammals; many studies report that such changes constitute a complex process involving numerous molecular mediators. In the present study, goat endometria at oestrus Day 5 and oestrus Day 15 were selected to systematically analyse the transcriptome using strand-specific Ribo-Zero RNA sequencing. Over 120 million high-quality paired-end reads were generated and 440 400 transcripts were identified in the endometrial tissue of dairy goats. In total, 489 differentially expressed mRNAs and 854 differentially expressed long non-coding RNAs were identified when comparing the endometrium at goat endometria at oestrus Day 5 and oestrus Day 15. Neurotensin was found to play a potentially important role in the non-pregnant goat endometrium during the oestrus cycle. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the cis -target genes of the differentially expressed long non-coding RNAs showed that GO : 0005198 (structural molecule activity) and ko04510 (focal adhesion) might be involved in cyclic endometrial changes. Taken together, the resulting transcriptomic profiles elucidate global trends in mRNA and lncRNA expression in non-pregnant endometria during the oestrus cycle in dairy goats. Ribo-Zero RNA-Seq is emerging as a powerful tool to identify potential factor for endometrium development. In this study, we selected the non-pregnant goat endometrium on Days 5 and 15 of oestrus to systematically analyse mRNA and lncRNA expression. The results of the present study provide essential transcriptome data as useful supplementary regarding the goat genome. [ABSTRACT FROM AUTHOR]

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. This study provides the first comprehensive analysis of long noncoding RNAs (lncRNAs) in goat endometrium at two developmental stages, which could have functional roles in the formation of endometrial receptivity. Importantly, we combine RNA‐Seq with detailed mechanistic studies to describe that lncRNA882 acts as a competing competing endogenous RNA (ceRNA) for miR‐15b, directly regulates the transforming growth factor‐b‐activated kinase 1 binding protein 3 (TAB3), and then indirectly regulates the level of leukemia inhibitory factor (LIF), which is helpful for the formation of endometrial receptivity in dairy goats. As the roles of candidate lncRNAs in goat endometrium have not yet been fully identified and understood, this study should provide valuable resource for further studies [ABSTRACT FROM AUTHOR]

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. A receptive endometrium is essential for embryo implantation in mammalian reproduction. This study shows that the circRNA-9119–miR-26a–prostaglandin-endoperoxide synthase 2 pathway may be a potential target to regulate the development of receptive endometrium. The findings of this study may provide essential information to support further research into the development of the endometrium and improve reproductive function and fecundity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity. Circular RNAs (circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes. Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5 (pre-receptive endometrium, PE) and three goats at gestational day 15 (receptive endometrium, RE). Overall, 21,813 circRNAs were identified, of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE, which suggested high stage-specificity. Further analysis found 334 differentially expressed circRNAs in the RE compared with PE (P < 0.05). The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression. Moreover, some circRNAs were regulated by estrogen (E2)/progesterone (P4) in endometrial epithelium cell lines (EECs) and endometrial stromal cell line (ESCs), and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4. Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation. [ABSTRACT FROM AUTHOR]