Dynamic intrauterine crosstalk promotes porcine embryo implantation during early pregnancy.

Dynamic crosstalk between the embryo and mother is crucial during implantation. Here, we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium, identifying 4 different lineages in embryos and 13 cell types in the endometrium. Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations, showing development from undifferentiated trophectoderm to polar and mural trophectoderm. Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation. Then, we developed a novel tool, ExtraCellTalk, generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells. These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.

Protein Dynamic Landscape of Pig Embryos during Peri-Implantation Development.

Properly developed embryos are critical for successful embryo implantation. The dynamic landscape of proteins as executors of biological processes in pig peri-implantation embryos has not been reported so far. In this study, we collected pig embryos from days 9, 12, and 15 of pregnancy during the peri-implantation stage for a PASEF-based quantitative proteomic analysis. In total, approximately 8000 proteins were identified. These proteins were classified as stage-exclusive proteins and stage-specific proteins, respectively, based on their presence and dynamic abundance changes at each stage. Functional analysis showed that their roles are consistent with the physiological processes of corresponding stages, such as the biosynthesis of amino acids and peptides at P09, the regulation of actin cytoskeletal organization and complement activation at P12, and the vesicular transport at P15. Correlation analysis between mRNAs and proteins showed a general positive correlation between pig peri-implantation embryonic mRNAs and proteins. Cross-species comparisons with human early embryos identified some conserved proteins that may be important in regulating embryonic development, such as STAT3, AP2A1, and PFAS. Our study provides a comprehensive overview of the pig embryo proteome during implantation, fills gaps in relevant developmental studies, and identifies some important proteins that may serve as potential targets for future research.

Effect of miR-143-3p from Extracellular Vesicles of Porcine Uterine Luminal Fluid on Porcine Trophoblast Cells.

Extracellular vesicles (EVs) in uterine luminal fluid (ULF) can reportedly affect the proliferation and migration function of porcine trophoblast cells (PTr2 cells) by mediating the maternal-fetal exchange of information. miR-143-3p is considered a crucial miRNA in early pregnancy in mammals; however, little is currently known about how it regulates the function of PTr2 cells. This study aimed to investigate the effects of ssc-miR-143-3p in ULF-EVs on the function of PTr2 cells during porcine embryo implantation. The uptake of ULF-EVs by PTr2 cells was confirmed, which significantly increased the expression of ssc-miR-143-3p. Ssc-miR-143-3p was found to facilitate the proliferation and migration of PTr2 cells in the CCK-8, EdU and wound-closure assays, while the opposite findings were observed after the knockdown of ssc-miR-143-3p. Bioinformatics analysis and the luciferase reporter assay showed that glycerol-3 phosphate dehydrogenase 2 (GDP2) was directly targeted by miR-143-3p. Inhibition of miR-143-3p was validated in mice to inhibit embryo implantation. In summary, ssc-miR-143-3p in ULF-EVs affects the proliferation and migration of PTr2 cells by mediating GPD2, thereby affecting embryo implantation.

A unique glimpse into the crosstalk between different epigenetic mechanisms in porcine embryonic development†.

The pig is an excellent animal model for simulating human physiology and a major animal for meat production and xenotransplantation. Therefore, researching porcine embryonic development is crucial for studying human reproductive diseases and improving litter size in commercial pigs. Embryonic development in pigs occurs under a complex regulatory mechanism, in which epigenetic regulatory mechanisms play an essential role. Recently, studies on the effects of epigenetic modifications on embryonic development have been conducted at different developmental stages and in different cell lines. Increasing evidence suggests that a certain amount of crosstalk exists between different epigenetic modifications. This review describes four regulatory mechanisms of epigenetics involved in porcine embryonic development: DNA methylation, histone modification, non-coding RNA function, and chromatin accessibility, and explores the possible crosstalk between them.

Non-Coding RNAs Regulate Spontaneous Abortion: A Global Network and System Perspective.

Spontaneous abortion is a common pregnancy complication that negatively impacts women's health and commercial pig production. It has been demonstrated that non-coding RNA (ncRNA) is involved in SA by affecting cell proliferation, invasion, apoptosis, epithelial-mesenchymal transformation (EMT), migration, and immune response. Over the last decade, research on ncRNAs in SA has primarily concentrated on micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In this review, we discuss recent ncRNA studies focused on the function and mechanism of miRNAs, lncRNAs, and circRNAs in regulating SA. Meanwhile, we suggest that a ceRNA regulatory network exists in the onset and development of SA. A deeper understanding of this network will accelerate the process of the quest for potential RNA markers for SA diagnosis and treatment.

Ferroptosis-related genes involved in animal reproduction: An Overview.

Ferroptosis is a new type of programmed cell death caused by excessive accumulation of iron-dependent lipid peroxidation products. Animal reproduction is a complex process affected by multiple genes, hormones, proteins, minerals, and the environmental factor. In order to better understand the potential regulatory mechanism of ferroptosis in animal reproduction, we collated multiple ferroptosis-related genes, which are expressed in sperms, oocytes, follicles, embryos, the placenta, and/or the uterus, Furthermore, the prospective role of ferroptosis in animal reproduction was discussed. Since some reproductive diseases were found to be correlated with ferroptosis, we suggest that ferroptosis will be a novel therapeutic target in the treatment of these diseases to help solve the problems that affect reproduction. At present, numerous scientific researches about ferroptosis are studied in human and rat models. Eventually, further ferroptosis research in common livestock, such as pigs and cattle, will provide theoretical guidance for improving livestock production.

Differential MicroRNA Expression Involved in Endometrial Receptivity of Goats.

Endometrial receptivity represents one of the leading factors affecting the successful implantation of embryos during early pregnancy. However, the mechanism of microRNAs (miRNAs) to establish goat endometrial receptivity remains unclear. This study was intended to identify potential miRNAs and regulatory mechanisms associated with establishing endometrial receptivity through integrating bioinformatics analysis and experimental verification. MiRNA expression profiles were obtained by high-throughput sequencing, resulting in the detection of 33 differentially expressed miRNAs (DEMs), followed by their validation through quantitative RT-PCR. Furthermore, 10 potential transcription factors (TFs) and 1316 target genes of these DEMs were obtained, and the TF-miRNA and miRNA-mRNA interaction networks were constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these miRNAs were significantly linked to establishing endometrial receptivity. Moreover, the fluorescence in situ hybridization (FISH) analysis, dual-luciferase report assay, and immunohistochemistry (IHC) analysis corroborated that chi-miR-483 could directly bind to deltex E3 ubiquitin ligase 3L (DTX3L) to reduce its expression level. In conclusion, our findings contribute to a better understanding of molecular mechanisms regulating the endometrial receptivity of goats, and they provide a reference for improving embryo implantation efficiency.