Trophectoderm biopsies of blastocysts for preimplantation genetic testing following in vitro fertilization and embryo culture increases epigenetic dysregulation in a mouse model
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ORGANISM(S): Mus musculus
PROVIDER: GSE225318 | GEO | 2024/04/24
REPOSITORIES: GEO
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Project description:Trophectoderm biopsy for preimplantation genetic testing (TEBx) impacts placental and embryonic health during early development, with some alterations resolving while others worsening later in development. We observed that at E12.5, IVF + TEBx had a worse outcome in terms of changes in DNA methylation and differential gene expression in placentas and whole embryos compared with IVF alone. These changes were reflected in alterations in placental morphology and blood vessel density. At E18.5, early changes in embryos were maintained or worsened, while molecular and morphological changes in the placenta were not different from the IVF group, except for changes in blood vessel density, which persisted. Of note is that most differences were sex specific. We conclude that TEBx has more detrimental effects in both mid-gestation placental and embryonic tissues, with changes in embryonic tissues persisting or worsening in later developmental stages compared to IVF alone. Additionally, consistent with previous work, we report sex differences in the observed effects. Finally, we identified that the addition of vitrification after TEBx has a more pronounced detrimental effect on placental and fetal health. Our findings provide additional support that more studies should be done to assess the impact of new procedures during ART to ensure healthy pregnancies and offspring outcomes.
2024-04-24 | GSE224844 | GEO
Project description:Trophectoderm biopsy for preimplantation genetic testing (TEBx) impacts placental and embryonic health during early development, with some alterations resolving while others worsening later in development. We observed that at E12.5, IVF + TEBx had a worse outcome in terms of changes in DNA methylation and differential gene expression in placentas and whole embryos compared with IVF alone. These changes were reflected in alterations in placental morphology and blood vessel density. At E18.5, early changes in embryos were maintained or worsened, while molecular and morphological changes in the placenta were not different from the IVF group, except for changes in blood vessel density, which persisted. Of note is that most differences were sex specific. We conclude that TEBx has more detrimental effects in both mid-gestation placental and embryonic tissues, with changes in embryonic tissues persisting or worsening in later developmental stages compared to IVF alone. Additionally, consistent with previous work, we report sex differences in the observed effects. Finally, we identified that the addition of vitrification after TEBx has a more pronounced detrimental effect on placental and fetal health. Our findings provide additional support that more studies should be done to assess the impact of new procedures during ART to ensure healthy pregnancies and offspring outcomes.
2024-04-24 | GSE225317 | GEO
Project description:Trophectoderm biopsies of blastocysts for preimplantation genetic testing following in vitro fertilization and embryo culture increases epigenetic dysregulation in a mouse model
| PRJNA934952 | ENA
Project description:Trophectoderm biopsies of blastocysts for preimplantation genetic testing following in vitro fertilization and embryo culture increases epigenetic dysregulation in a mouse model [array]
| PRJNA932777 | ENA
Project description:Trophectoderm biopsies of blastocysts for preimplantation genetic testing following in vitro fertilization and embryo culture increases epigenetic dysregulation in a mouse model [RNA-seq]
| PRJNA934960 | ENA
Project description:Embryo chromosomal abnormalities are considered as the main cause of low pregnancy rate for in vitro fertilization (IVF). Recently, a new metric of success in assisted reproductive technology, that is, the ability to achieve at least 1 euploid blastocyst for transfer, has been brought into focus among clinicians. Our study aimed to investigate the effects of different factors on the euploidy of blastocysts undergoing IVF and preimplantation genetic testing (PGT). This retrospective observational study included 493 cycles underwent IVF/intracytroplasmatic sperm injection intended to obtain trophectoderm biopsy for PGT from June 2016 to December 2019 at a single academic fertility center. Logistic regression was adopted to analyze the clinical characteristics and embryonic data related to the ability to achieve at least 1 euploid blastocyst for transfer. The study took 1471 blastocysts from 493 cycles as samples for PGT. Among them, 149 cycles (30.22%) had no euploid blastocyst and 344 cycles (69.78%) had at least 1 euploid blastocyst. A multivariate logistic analysis suggested that maternal age >36, abnormal parental karyotype, nonfirst cycles and blastocysts number per cycle <3 were the risk factors for no euploid blastocyst. The parental karyotype, maternal age, number of cycles, and number of blastocysts per cycle were the dominant factors affecting the ability to achieve at least 1 euploid blastocyst for transfer and therefore could be regarded as potential predictors for genetic counseling.
| S-EPMC9239646 | biostudies-literature
Project description:BackgroundIn preimplantation mammalian development the transcription factor Sox2 (SRY-related HMG-box gene 2) forms a complex with Oct4 and functions in maintenance of self-renewal of the pluripotent inner cell mass (ICM). Previously it was shown that Sox2-/- embryos die soon after implantation. However, maternal Sox2 transcripts may mask an earlier phenotype. We investigated whether Sox2 is involved in controlling cell fate decisions at an earlier stage.Methods and findingsWe addressed the question of an earlier role for Sox2 using RNAi, which removes both maternal and embryonic Sox2 mRNA present during the preimplantation period. By depleting both maternal and embryonic Sox2 mRNA at the 2-cell stage and monitoring embryo development in vitro we show that, in the absence of Sox2, embryos arrest at the morula stage and fail to form trophectoderm (TE) or cavitate. Following knock-down of Sox2 via three different short interfering RNA (siRNA) constructs in 2-cell stage mouse embryos, we have shown that the majority of embryos (76%) arrest at the morula stage or slightly earlier and only 18.7-21% form blastocysts compared to 76.2-83% in control groups. In Sox2 siRNA-treated embryos expression of pluripotency associated markers Oct4 and Nanog remained unaffected, whereas TE associated markers Tead4, Yap, Cdx2, Eomes, Fgfr2, as well as Fgf4, were downregulated in the absence of Sox2. Apoptosis was also increased in Sox2 knock-down embryos. Rescue experiments using cell-permeant Sox2 protein resulted in increased blastocyst formation from 18.7% to 62.6% and restoration of Sox2, Oct4, Cdx2 and Yap protein levels in the rescued Sox2-siRNA blastocysts.Conclusion and significanceWe conclude that the first essential function of Sox2 in the preimplantation mouse embryo is to facilitate establishment of the trophectoderm lineage. Our findings provide a novel insight into the first differentiation event within the preimplantation embryo, namely the segregation of the ICM and TE lineages.
| S-EPMC2980489 | biostudies-literature
Project description:Tetraploid complementation is an ideal method for demonstrating the differentiation potential of pluripotent stem cells. In this study, we selected the most efficient tetraploid production method for porcine embryos and investigated whether tetraploid blastomere aggregation could enhance the quality of tetraploid embryos. Three methods were investigated to produce tetraploid embryos: First, tetraploid embryos were produced using electro-fusion of two-cell stage parthenogenetic blastomere (FUTP). Second, somatic cell was injected into the mature oocyte and fused to produce tetraploid embryos. Third, oocytes were matured with Cytochalasin B (CB) for the late 22 h of in vitro maturation to inhibit the first polar body (PB1). Following that, non-PB1 oocytes were treated with CB for 4 h after parthenogenetic activation. There was no significant difference in the blastocyst development rate and tetraploid production rate of the embryos produced through the three methods. However, FUTP-derived blastocysts had a significantly lower percentage of apoptotic cells compared to other methods. The developmental competence of embryos, expression of trophectoderm cell marker genes, and distribution of YAP1 protein were investigated in tetraploid embryos produced using the FUTP method. The FUTP method most effectively prevented apoptosis during porcine tetraploid embryo formation. Tetraploid aggregation-derived blastocysts have a high proportion of trophectoderm with increased expression of the CDX2 mRNA and high YAP1 intensity. High-quality blastocysts derived from a tetraploid embryo aggregation can serve as suitable source material for testing the differentiation potential of pluripotent stem cells for blastocyst complementation in pigs.
| S-EPMC10687364 | biostudies-literature
Project description:Background Previous studies suggested that non-invasive preimplantation genetic testing (niPGT) for intracytoplasmic sperm injection (ICSI) blastocysts can be used to identify chromosomal ploidy and chromosomal abnormalities. Here, we report the feasibility and performance of niPGT for conventional in vitro fertilization (IVF) blastocysts. Methods This was a prospective observational study. In the preclinical stage, whole genome amplification and NGS were performed using the sperm spent culture medium (SCM). Then, trophectoderm (TE) biopsies and corresponding SCM derived from 27 conventional IVF monopronuclear embryos were collected. In the clinical stage, samples from 25 conventional IVF cycles and 37 ICSI cycles from April 2020–August 2021 were collected for performance evaluation. Results Preclinically, we confirmed failed sperm DNA amplification under the current amplification system. Subsequent niPGT from the 27 monopronuclear blastocysts showed 69.2% concordance with PGT results of corresponding TE biopsies. In the clinical stage, no paternal contamination was observed in any of the 161 SCM samples from conventional IVF. While maternal contamination was observed in 29.8% (48/161) SCM samples, only 2.5% (4/161) samples had a contamination ratio ≥ 50%. Compared with that of TE biopsy, the performances of NiPGT from 161 conventional IVF embryos and 122 ICSI embryos were not significantly different (P > 0.05), with ploidy concordance rates of 75% and 74.6% for IVF and ICSI methods, respectively. Finally, evaluation of the euploid probability of embryos with different types of niPGT results showed prediction probabilities of 82.8%, 77.8%, 62.5%, 50.0%, 40.9% and 18.4% for euploidy, sex-chromosome mosaics only, low-level mosaics, multiple abnormal chromosomes, high-level mosaics and aneuploidy, respectively. Conclusions Our research results preliminarily confirm that the niPGT approach using SCM from conventional IVF has comparable performance with ICSI and might broadening the application scope of niPGT. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03596-0.
| S-EPMC9441092 | biostudies-literature
Project description:In addition to the potential for multiple pregnancy, spontaneous conception during in vitro fertilization (IVF) can lead to undesired genetic outcomes. We present a case of a patient undergoing IVF with the intention of subsequent frozen embryo transfer after preimplantation genetic testing (PGT). Unprotected intercourse 6 days prior to egg retrieval resulted in a spontaneous pregnancy before the opportunity for embryo transfer. This case report highlights that spontaneous conception during IVF compromises the ability to transfer embryos that are euploid, unaffected by single gene disorders, or intended for gender balancing within a family when desired.
| S-EPMC6699353 | biostudies-literature