Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse

Laren Narapareddy, Eric A. Rhon-Calderon, Lisa A. Vrooman, Josue Baeza, Duy K. Nguyen, Clementina Mesaros, Yemin Lan, Benjamin A. Garcia, Richard M. Schultz, Marisa S. Bartolomei

Research output: Contribution to journalArticlepeer-review

Abstract

Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, there is increasing concern about the long-term and sex-specific health implications. Augmenting our IVF mouse model to longitudinally investigate metabolic outcomes in offspring from optimal neonatal litter sizes, we found sex-specific metabolic outcomes in IVF offspring. 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 adult liver transcriptomics and proteomics, 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.

Original languageEnglish (US)
Article numbere21523
JournalFASEB Journal
Volume35
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • assisted reproductive technologies
  • developmental origins of health and disease
  • long-term health
  • metabolic outcomes
  • sex-specific

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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