FGFR1 regulates trophectoderm development and facilitates blastocyst implantation.
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ABSTRACT:
SUBMITTER: Kurowski A
PROVIDER: S-EPMC6370302 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
FGFR1 regulates trophectoderm development and facilitates blastocyst implantation.
Kurowski Agata A Molotkov Andrei A Soriano Philippe P
Developmental biology 20181212 1
FGF signaling plays important roles in many aspects of mammalian development. Fgfr1<sup>-/-</sup> and Fgfr1<sup>-/-</sup>Fgfr2<sup>-/-</sup> mouse embryos on a 129S4 co-isogenic background fail to survive past the peri-implantation stage, whereas Fgfr2<sup>-/-</sup> embryos die at midgestation and show defects in limb and placental development. To investigate the basis for the Fgfr1<sup>-/-</sup> and Fgfr1<sup>-/-</sup>Fgfr2<sup>-/-</sup> peri-implantation lethality, we examined the role of FGFR ...[more]
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Project description:Mechanisms of implantation such as determination of the attachment pole, fetal-maternal communication, and underlying causes of implantation failure are largely unexplored. Here, we performed single-cell RNA sequencing on peri-implantation embryos from both humans and mice to explore trophectoderm (TE) development and embryo-endometrium cross-talk. We found that the transcriptomes of polar and mural TE diverged after embryos hatched from the zona pellucida in both species, with polar TE being more mature than mural TE. The implantation poles show similarities in cell cycle activities, as well as in expression of genes critical for implantation and placentation. Embryos that either fail to attach in vitro or fail to implant in vivo show abnormalities in pathways related to energy production, protein metabolism, and 18S ribosomal RNA m6A methylation. These findings uncover the gene expression characteristics of humans and mice TE differentiation during the peri-implantation period and provide new insights into embryo implantation.
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Project description:BackgroundA key step in embryo implantation is the adhesion to and invasion of the endometrium by the blastocyst trophectoderm. The envelope proteins of HERV-W and -FRD (human endogenous retrovirus-W and -FRD), syncytin-1 and syncytin-2, are mainly distributed in the placenta, and play important roles in the development of the placenta. The placenta originates from the trophectoderm of the blastocyst. It is unclear whether the envelope proteins of HERV-W and -FRD have an effect on the development of the trophectoderm and whether they have any association with the implantation of the blastocyst.MethodsThe whole-genome amplification products of the human blastocyst trophectoderm were used to measure the copy number of syncytin-1 and syncytin-2 using real time qPCR. In addition, clinical data associated with the outcome of pregnancies was collected, and included age, body mass index (BMI), basic follicle stimulating hormone(bFSH), rate of primary infertility and oligo-astheno-teratospermia, the thickness of the endometrium on the day of endometrial transformation, the levels of estrogen and progestin on the transfer day, the days and the morphological scores of the blastocysts. The expression of mRNA and the copy numbers of syncytin-1 and syncytin-2 in H1 stem cells, and in differentiated H1 cells, induced by BMP4, were measured using real time qPCR.ResultsThe relative copy number of syncytin-1 in the pregnant group (median: 424%, quartile: 232%-463%, p < 0.05) was significantly higher than in the non-pregnant group (median: 100%, quartile: 81%-163%). There was a correlation (r s = 0.681, p < 0.001) between the copy number of syncytin-1 and blastocyst implantation after embryo transfer. As the stem cells differentiated, the expression of NANOG mRNA decreased, and the expression of caudal type homeobox 2(CDX2) and β-human chorionic gonadotropin (β-hCG) mRNAs increased. Compared to the undifferentiated cells, the relative expression of the syncytin-1 mRNA was 1.63 (quartile: 0.59-6.37, p > 0.05), 3.36 (quartile: 0.85-14.80, p > 0.05), 10.85 (quartile: 3.39-24.46, p < 0.05) and 67.81 (quartile: 54.07-85.48, p < 0.05) on day 1, 3, 5 and 7, respectively, after the differentiation. The relative expression of syncytin-2 was 5.34 (quartile: 4.50-10.30), 7.90 (quartile: 2.46-14.01), 57.44 (quartile: 38.35-103.87) and 344.76 (quartile: 267.72-440.10) on day 1, 3, 5 and 7, respectively, after the differentiation (p < 0.05). The copy number of syncytin-1 increased significantly during differentiation.ConclusionPreceding the transfer of frozen embryos, the increased copy number of syncytin-1 in the blastocyst trophectoderm was associated with good outcomes of pregnancies.
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2022-08-01 | GSE133200 | GEO
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2021-09-15 | GSE177689 | GEO