Bovine endometrium drives and responds to divergence of in vitro produced conceptus biochemistry
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ABSTRACT:
PROVIDER: PRJNA1256274 | ENA |
REPOSITORIES: ENA
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Project description:In vitro produced (IVP) bovine embryos are used to enhance herd genetics and support advanced reproductive technologies, however, less than 40% survive the first month of gestation after transfer to the surrogate. While the biochemical consequences of in vitro culture on the embryo before transfer have been well documented, less is known after transfer when the embryo interacts with the endometrium and pregnancy failure occurs. To investigate this, we utilized a Day 16 trophectoderm-endometrial mono-culture and co-culture system, integrating transcriptomic and proteomic analyses, to compare crosstalk between the IVP or in vivo derived (IVD) bovine conceptus and endometrium. We found that the IVP conceptus transcriptome (differentially expressed genes; DEG), diverged from the IVD conceptus but only after co-culture with endometrium (377 DEG; FDR < 0.05). Further, of the IVP conceptus DEG, 81 genes (21%) were associated with abnormal embryonic or fetal development. Significant biological processes associated with abundant endometrial DEG induced by IVP conceptuses were related to GTPase activity and the inflammatory response (FDR < 0.01), the latter of which may be associated with increased MHC class II expression, which was specific to IVP conceptuses. Proteomic analysis of the culture media identified 1,031 and 604 differentially abundant proteins (FDR < 0.05) associated with the IVD and IVP conceptus-endometrial co-cultures, respectively, compared to endometrium alone, indicating the proteomic environment surrounding the IVP conceptus may be suboptimal. Collectively, compared to the IVD conceptus, it appears the endometrium drives and responds to divergence of IVP conceptus biochemistry, likely contributing to pregnancy failure.
2025-07-31 | GSE295732 | GEO
Project description:Early embryo loss affects all mammalian species, including humans and agriculturally important food-producing mammals such as cattle. The developing conceptus (embryo and extra-embryonic membranes) secretes factors which modify the endometrium and can be critical for early pregnancy processes such maternal recognition of pregnancy (MRP) and enhancing uterine receptivity to implantation. For example, a competent bovine conceptus secretes IFNT to initiate MRP. The bovine conceptus also secretes other proteins at the time of MRP, including CAPG and PDI, which are highly conserved among placental mammals. We have previously shown that these proteins act upon the endometrium to modulate receptivity, embryo development, and implantation in species with different implantation strategies (humans and cattle). We hypothesise that developing a novel 3D bovine endometrium on a chip system will enhance our understanding of the role of conceptus-derived factors in altering the endometrium and/or ULF secretion. Here we have developed a 3D bovine endometrium on a chip system, comprising both stromal and epithelial cell culture combined with culture medium flow better mimics the in vivo endometrium and exposure to conceptus-derived factors than conventional 2D endometrial cell culture. We have demonstrated that the conceptus-derived proteins CAPG and PDI modulate the endometrial transcriptome and secretory response to promote pathways associated with early pregnancy and alter ULF composition. This work highlights the critical need for more robust and in vivo-like culture systems to study endometrial-conceptus interactions in vitro to further investigate the role of conceptus derived factors for pregnancy success.
2025-05-19 | PXD059725 | Pride
Project description:Early embryo loss affects all mammalian species, including humans and agriculturally important food-producing mammals such as cattle. The developing conceptus (embryo and extra-embryonic membranes) secretes factors which modify the endometrium and can be critical for early pregnancy processes such maternal recognition of pregnancy (MRP) and enhancing uterine receptivity to implantation. For example, a competent bovine conceptus secretes IFNT to initiate MRP. The bovine conceptus also secretes other proteins at the time of MRP, including CAPG and PDI, which are highly conserved among placental mammals. We have previously shown that these proteins act upon the endometrium to modulate receptivity, embryo development, and implantation in species with different implantation strategies (humans and cattle). We hypothesise that developing a novel 3D bovine endometrium on a chip system will enhance our understanding of the role of conceptus-derived factors in altering the endometrium and/or ULF secretion. Here we have developed a 3D bovine endometrium on a chip system, comprising both stromal and epithelial cell culture combined with culture medium flow better mimics the in vivo endometrium and exposure to conceptus-derived factors than conventional 2D endometrial cell culture. We have demonstrated that the conceptus-derived proteins CAPG and PDI modulate the endometrial transcriptome and secretory response to promote pathways associated with early pregnancy and alter ULF composition. This work highlights the critical need for more robust and in vivo-like culture systems to study endometrial-conceptus interactions in vitro to further investigate the role of conceptus derived factors for pregnancy success.
2025-05-19 | GSE287563 | GEO
Project description:This study aimed to identify bovine conceptus-induced modifications to the endometrial transcriptome both dependent and independent of interferon tau (IFNT), dependent on conceptus origin [in vitro fertilization (IVF) or artifical insemination (AI) derived blastocysts] and dependent on conceptus sex. Major findings include identification of genes differentially expressed in endometrium in response to the conceptus but independent of IFNT and genes differentially expressed in endometrium in response to AI vs. IVF and male vs. female conceptuses.
2018-08-17 | GSE118672 | GEO
Project description:The bovine conceptus elongates near Day 16 of development and releases interferon-tau (IFNT), disrupting the endometrial luteolytic mechanism to sustain luteal P4 and pregnancy. Conceptus factors other than IFNT modify local endometrial activities in support of pregnancy; however, the microenvironment is largely uncharacterized. We utilized a bovine conceptus-endometrial culture system to elucidate the microenvironment in the form of RNA and protein. Estrus synchronized heifers remained cyclic (13) or were inseminated (9) to produce Day 16 cyclic endometrium and elongating conceptuses, respectively. Conceptus sections and cyclic endometrium were then used to generate tissue cultures in 1 mL of medium: (1) no tissue (Control Med; n=7), (2) mono-cultured conceptus (Conceptus; n=9), (3) mono-cultured endometrium (Endo; n=13), or (4) Endo-Conceptus co-culture (n=15). After 12 h, tissue RNA was sequenced (RNA-Seq) and media underwent proteomic analysis (LC-MS/MS). Compared to Conceptus and Endo, co-cultured conceptus and endometrial tissue contained 3,400 and 4,575 differentially expressed genes (DEG), respectively (P ≤ 0.01). Upregulated endometrial DEG, independent of IFNT, were associated with transcription whereas upregulated conceptus DEG were associated with protein homeostasis and metabolism (P ≤ 0.001).
2024-06-30 | GSE256172 | GEO
Project description:A bovine 3D endometrium-on-a-chip revelas the role fo conceptus-derived factors CAPG and PDI in conceptus-endometrium communication
| PRJNA1213752 | ENA
Project description:A major unresolved issue in the cloning of mammals by somatic cell nuclear transfer (SCNT) is the mechanism by which the process fails after embryos are transferred to the uterus of recipients, prior to or during the implantation window. We investigated this problem by using RNA-seq to compare the transcriptomes in cattle conceptuses produced by SCNT and artificial insemination (AI) at d18 (pre-implantation) and d34 (post-implantation) of gestation. In addition, endometrium was profiled in order to identify the communication pathways that might be affected by the presence of a cloned conceptus, ultimately leading to mortality prior to or during the implantation window. At d18, the effects on the transcriptome associated with SCNT were massive, involving more than 5,000 differentially expressed genes (DEGs). Among them are 121 genes that have embryonic lethal phenotypes in mice, cause defects in trophoblast and placental development, and/or affect conceptus survival in mice. In endometria at d18, <0.4% of expressed genes were affected by the presence of a cloned conceptus, whereas at d34, ~36% and <0.7% of genes were differentially expressed in intercaruncular and caruncular tissues, respectively. Functional analysis of DEGs in placental and endometrial tissues suggests a major disruption of signaling between the cloned conceptus and the endometrium, particularly the intercaruncular tissue. Our results support a bottleneck model for cloned conceptus survival during the peri-implantation period determined by gene expression levels in extra-embryonic tissues and the endometrial response to altered signaling from clones.
2016-11-26 | GSE74152 | GEO
Project description:We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferredBos taurus taurusembryos of different origin:In vivo(high developmental potential (IV)),in vitro(intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), intoBos taurus indicusrecipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response toin vivoVsin vitroandin vivoVs cloned conceptuses (1153 and 334DEGs respectively) with limited differences betweenin vitroVs cloned conceptuses (36 DEGs). miRNA cargo was similar between all three groups (426 common cargo) differences betweenin vivoand cloned (8 miRNAs), andin vivoandin vitro(6 miRNAs) observed. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changes to the proteomic content of target cells (96, and 85 respectively) of which mRNAs are altered in the endometriumin vivo(PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.
2025-01-21 | GSE256161 | GEO
Project description:Transcriptome of endometrium in response to conceptus proteins in dairy cattle [ENDO]
| PRJNA1010688 | ENA
Project description:Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern pre-implantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil (CO) vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many of the differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of pre-implantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and pre-implantation blastocyst growth and development in sheep.
2009-08-01 | GSE17401 | GEO