Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse.

Bartolomei, M. S.; Narapareddy, L.; Schultz, R. M.; Garcia, B. A.; Rhon-Calderon, E.; Vrooman, L. A.; Nguyen, D.; Baeza, J.; Lan, Y.

doi:10.1101/2020.09.23.309989

bioRxiv · 10.1101/2020.09.23.309989

Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse.

Bartolomei, M. S.·Narapareddy, L.·Schultz, R. M.·Garcia, B. A.·Rhon-Calderon, E.·Vrooman, L. A.·Nguyen, D.·Baeza, J.·Lan, Y.

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Abstract

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-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.

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Bartolomei, M. S., Narapareddy, L., Schultz, R. M., Garcia, B. A., Rhon-Calderon, E., Vrooman, L. A., Nguyen, D., Baeza, J., Lan, Y.. 2020-09-23. Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse.. https://doi.org/10.1101/2020.09.23.309989

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