Hepatic RNA sequence in male mice offspring conceived by in-vitro Fertilization and Frozen-thawed Embryo Transfer
Ontology highlight
ABSTRACT: Our study reported an increased risk of metabolic disorders in in-vitro Fertilization and Frozen-thawed Embryo Transfer (IVF-FET) conceived offspring compared with those born after IVF-ET. To explore the underlying mechanisms of the aberrant metabolism in male offspring conceived by IVF and FET compared with natural conceived (NC), we performed the RNA-sequencing of livers from three groups. We performed GSEA analysis. The results suggested more severe alterations in the expression of genes involved in insulin resistance pathway in the FET-chow group than that in the IVF-chow group.
Project description:Frozen-thawed embryo transfer (FET) is increasingly available for the improvement of the success rate of assisted reproductive technologies other than fresh embryo transfer (ET). There have been numerous findings that FET provides better obstetric and perinatal outcomes. However, the birth weight of infants conceived using FET is heavier than that of those conceived via ET. In addition, some reports have suggested that FET is associated with perinatal diseases such as placenta accreta and pregnancy-induced hypertension and a decrease in the sex ratio of male infants. These phenotypic alterations are caused by epigenetic alterations. MicroRNAs (miRNAs) are one of epigenetic modifications and dysregulation of miRNAs due to the environment in utero leads to placenta-associated diseases in infants and subsequently chronic diseases later in life. In this study, we compared miRNA expression profiles in the placentas originated from intracytoplasmic sperm injection and FET (ICSI-FET), intracytoplasmic sperm injection and ET (ICSI-ET) and from intracytoplasmic sperm injection and FET (ICSI-FET), intracytoplasmic sperm injection and ET (ICSI-ET) and spontaneous pregnancies (SP).
Project description:Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that contribute to the sex-specfic phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.
Project description:Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that are associated with the sex-specific phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.
Project description:In vitro fertilization (IVF) is a non-coital method of conception used to treat infertility. Although safe, IVF has been associated with adverse outcomes in the fetus, placenta, and adult life, but studies focusing on the male reproductive system are limited. Here, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated three developmental stages: 18.5-day fetuses and 12- and 39-week adults. Regardless of age, we observed changes in the testicular-to-body weight ratio, serum testosterone levels, testicular morphology, transcriptome, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF and naturally conceived males with wild-type females. Offspring from IVF males exhibited a decreased fetal weight-to-placental weight ratio regardless of sex. At 12-weeks-of-age, offspring showed higher body weights, differences in glucose, triglycerides, insulin, total cholesterol, HDL and LDL/VLDL levels. Both sexes showed changes in gene expression in liver, testes and ovaries, and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations and transmit defects multigenerationally. These experiments contribute to our understanding of the long-term impacts of IVF on adult offspring health.
Project description:In vitro fertilization (IVF) is a non-coital method of conception used to treat infertility. Although safe, IVF has been associated with adverse outcomes in the fetus, placenta, and adult life, but studies focusing on the male reproductive system are limited. Here, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated three developmental stages: 18.5-day fetuses and 12- and 39-week adults. Regardless of age, we observed changes in the testicular-to-body weight ratio, serum testosterone levels, testicular morphology, transcriptome, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF and naturally conceived males with wild-type females. Offspring from IVF males exhibited a decreased fetal weight-to-placental weight ratio regardless of sex. At 12-weeks-of-age, offspring showed higher body weights, differences in glucose, triglycerides, insulin, total cholesterol, HDL and LDL/VLDL levels. Both sexes showed changes in gene expression in liver, testes and ovaries, and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations and transmit defects multigenerationally. These experiments contribute to our understanding of the long-term impacts of IVF on adult offspring health.
Project description:In vitro fertilization (IVF) is a non-coital method of conception used to treat infertility. Although safe, IVF has been associated with adverse outcomes in the fetus, placenta, and adult life, but studies focusing on the male reproductive system are limited. Here, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated three developmental stages: 18.5-day fetuses and 12- and 39-week adults. Regardless of age, we observed changes in the testicular-to-body weight ratio, serum testosterone levels, testicular morphology, transcriptome, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF and naturally conceived males with wild-type females. Offspring from IVF males exhibited a decreased fetal weight-to-placental weight ratio regardless of sex. At 12-weeks-of-age, offspring showed higher body weights, differences in glucose, triglycerides, insulin, total cholesterol, HDL and LDL/VLDL levels. Both sexes showed changes in gene expression in liver, testes and ovaries, and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations and transmit defects multigenerationally. These experiments contribute to our understanding of the long-term impacts of IVF on adult offspring health.
Project description:Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF), its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis, a high number of embryos containing abnormal cells can pass this strong selection barrier. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF- and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF- and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.
Project description:The study included 47 newborn twins conceived though in vitro fertilisation (IVF) and 60 non-IVF-conceived twins from the Peri/postnatal Epigenetic Twins Study (PETS). Cord blood was collected at birth and used to process mononuclear cells. Whole blood cells (WBCs) from cord blood of 98 twins (40 IVF and 58 non-IVF) and cord blood mononuclear cells (CBMCs) of 82 twins (35 IVF and 47 non-IVF) were subjected to DNA methylation profiling. Methylated DNA immunoprecipitation followed by deep sequencing (MeDIP-seq) was applied to generate genome-wide DNA methylation profiles in a total of 180 samples. Single-end reads were mapped onto hg19 using BWA. Methylation levels were quantified using MEDIPS and used to identify IVF-associated differentially methylated regions.
Project description:Next generation sequencing was perfomed to identify differentially expressed gene in Placental tissue samples from IVF-ET assisted or natural conceived pregnancies