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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.
2025-03-31 | GSE280162 | GEO
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.
2025-03-31 | GSE280285 | GEO
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.
2025-03-31 | GSE290562 | GEO
Project description:In Vitro Fertilization induces reproductive changes in male mouse offspring and has multigenerational effects
| PRJNA1177752 | ENA
Project description:In Vitro Fertilization induces reproductive changes in male mouse offspring and has multigenerational effects [array]
| PRJNA1176627 | ENA
Project description:In Vitro Fertilization induces reproductive changes in male mouse offspring and has multigenerational effects [RNA-Seq]
| PRJNA1177755 | ENA
Project description:In Vitro Fertilization induces reproductive changes in male mouse offspring and has multigenerational effects [RNA-seq II]
| PRJNA1228628 | ENA
Project description:Prenatal synthetic glucocorticoids (sGC) are administered to pregnant women at risk of delivering preterm, approximately 10% of all pregnancies. Animal studies have demonstrated that offspring exposed to elevated glucocorticoids, either by administration of sGC or as a result of maternal stress, are at increased risk of developing behavioral, endocrine, and metabolic abnormalities. DNA methylation is a covalent modification of DNA that plays a critical role in long-lasting programming of gene expression. Here we tested the hypothesis that prenatal sGC treatment has both acute and long-term effects on DNA methylation states in the fetus and offspring and that these effects extend into a subsequent generation. Pregnant guinea pigs were treated with sGC in late gestation, and methylation analysis by luminometric methylation assay was undertaken in organs from fetuses and offspring across two generations. Expression of genes that modify the epigenetic state were measured by quantitative real-time PCR. Results indicate that there are organ-specific developmental trajectories of methylation in the fetus and newborn. Furthermore, these trajectories are substantially modified by intrauterine exposure to sGC. These sGC-induced changes in DNA methylation remain into adulthood and are evident in the next generation. Furthermore, prenatal sGC exposure alters the expression of several genes encoding proteins that modulate the epigenetic state. Several of these changes are long lasting and are also present in the next generation. These data support the hypothesis that prenatal sGC exposure leads to broad changes in critical components of the epigenetic machinery and that these effects can pass to the next generation.
| S-EPMC3422463 | biostudies-literature
Project description:ObjectivesWe generated an in vitro fertilization and embryo transfer (IVF-ET) mouse model to investigate the molecular mechanism underlying the abnormal lipid metabolism found in IVF-ET offspring.MethodsThe glucose metabolism levels of offspring were assessed by glucose tolerance test (GTT), insulin tolerance test (ITT), and pyruvate tolerance test (PTT). The lipid metabolism levels were assessed by triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). RNA-seq was performed on liver tissues. mRNA and protein expression of relevant genes was verified by the quantitative real-time PCR and protein immunoblotting. HepG2 cells were transfected with either interfering RNA or overexpression plasmids to investigate the gene functions.ResultsCompared to the control, male IVF-ET offspring showed: 1) higher body, liver, and epididymal white adipose tissue weight; 2) disrupted glucolipid metabolism with abnormal GTT, ITT, and PTT; 3) significantly decreased GDF15 along with increased RGS16. Furthermore, phosphorylation of ERK1/2 and AKT was significantly reduced. In HepG2 cells, knockdown of GDF15 caused an abnormally increased RGS16 and decreased phosphorylation of ERK1/2 and AKT, accompanied by increased lipid deposition. In contrast, overexpression of GDF15 reduced expression of RGS16. Simultaneous knockdown of both GDF15 and RGS16 reversed lipid deposition.ConclusionsDown-regulation of GDF15 results in elevated RGS16, which causes the weakening of the downstream ERK1/2 and AKT phosphorylation, leading to abnormal lipid metabolism in the livers of IVF-ET male offspring. This suggests that the GDF15-RGS16-p-ERK1/2/p-AKT pathway plays a crucial role in liver lipid deposition in IVF-ET male offspring and could be a therapeutic target.
| S-EPMC9641458 | biostudies-literature
Project description:Frozen and thawed embryo transfer (FET) is currently widely applied in routine assisted reproductive technology (ART) procedure. It is of great necessity to assess the safety of FET and investigate the long-term effect including glucose metabolism on FET-conceived offspring. The mouse model is a highly efficient method to figure out the relationship between the process of FET and offspring health. In this study, we obtained mouse offspring of natural conception (NC), in vitro fertilization (IVF), and FET. Glucose and insulin tolerance test (GTT/ITT) were performed on both chow fed or high fat diet (HFD) fed offspring to examine the glucose metabolism status. We detected hepatic PI3K/AKT pathway by western blotting and transcriptome status by RNA-sequencing. Impaired glucose tolerance (IGT) and decreased insulin tolerance were occurred in FET conceived male offspring. After challenged with the HFD-fed, male offspring in FET group performed earlier and severer IGT than IVF group. Furthermore, higher HOMA-IR index and higher serum insulin level post glucose injected in FET-chow group suggested the insulin resistance status. The PI3K/AKT signaling pathway, the major pathway of insulin in the liver, were also disrupted in FET group. Transcriptomics of the liver reveals significantly downregulated in glucose metabolic process and insulin resistance in the FET-chow group. In our study, FET-conceived male mouse offspring presented glucose metabolism dysfunction mainly manifesting insulin resistance. The hepatic insulin signaling pathway were in concordance with reduced glycogen synthesis, increased glycolysis and enhanced gluconeogenesis status in FET-conceived male offspring.
| S-EPMC7900417 | biostudies-literature