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Ultra-low oxygen tension during in vitro fertilization improves embryonic and adult outcomes [RNA-seq]

ABSTRACT: Embryo culture, a required step during in vitro fertilization (IVF), exposes developing embryos to altered environmental conditions not normally experienced in vivo, including altered oxygen (O2) tension. Importantly, O2 influences gene expression, metabolism, and the activity of important epigenetic enzymes. In clinics today, the lowest O2 tension used during embryo culture is 5%, despite evidence that portions of the mammalian female reproductive tract have O2 levels as low at 2%. This suggests lower O2 may better mimic the in vivo environment, and thus lead to improved pre- and postnatal outcomes in IVF-conceived offspring. Using our validated IVF mouse model, we show embryo culture at 2% O2 compared to culture under 5% O2 significantly improves cell numbers and the chromatin landscape in preimplantation embryos, fetal and placental development during gestation, and metabolic functions in adulthood. Overall, these results suggest embryo culture with 2% O2 improves adverse outcomes after IVF, and support the need to improve these procedures.

ORGANISM(S): Mus musculus

PROVIDER: GSE335222 | GEO | 2026/09/15

REPOSITORIES: GEO

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Ultra-low oxygen tension during in vitro fertilization improves embryonic and adult outcomes [methylation array]

Project description:Embryo culture, a required step during in vitro fertilization (IVF), exposes developing embryos to altered environmental conditions not normally experienced in vivo, including altered oxygen (O2) tension. Importantly, O2 influences gene expression, metabolism, and the activity of important epigenetic enzymes. In clinics today, the lowest O2 tension used during embryo culture is 5%, despite evidence that portions of the mammalian female reproductive tract have O2 levels as low at 2%. This suggests lower O2 may better mimic the in vivo environment, and thus lead to improved pre- and postnatal outcomes in IVF-conceived offspring. Using our validated IVF mouse model, we show embryo culture at 2% O2 compared to culture under 5% O2 significantly improves cell numbers and the chromatin landscape in preimplantation embryos, fetal and placental development during gestation, and metabolic functions in adulthood. Overall, these results suggest embryo culture with 2% O2 improves adverse outcomes after IVF, and support the need to improve these procedures.

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Effect of embryo in vitro culture on mESC transcriptome.

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Effect of embryo in vitro culture on mESC transcriptome.

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Project description:In this study, we utilized single-nucleus RNA sequencing to quantify alterations in the gene expression programs of mouse placentas conceived through in vitro fertilization (IVF). We identified genetic programs exhibiting both global and cell type specific differences between IVF and natural in vivo fertilization groups. Gene set enrichment analysis revealed pathways associated with parietal trophoblast giant cell differentiation and implicated in the regulation of lactation (placental lactogens), along with Hypoxia-inducible factor dependent gene expression. Importantly, IVF-derived conceptuses showed increased abortion rates when their surrogate mothers were exposed to hypoxia (10.5% O2) during pregnancy (from E7.5 to 12.5). Collectively, our findings shed light on the cellular and molecular underpinnings driving differences in pregnancy outcomes associated with these conception methods and indicate that IVF can sensitize embryos to additional stressful events, as proposed by the developmental origin of health and disease hypothesis.

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Project description: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.

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Project description:The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

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In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages

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2018-12-31 | GSE93353 | GEO

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