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Author Notes:

Marisa Bartolomei, Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, 9-122 Smilow Center for Translational Research, 3400 Civic Center Blvd., Philadelphia, PA 19104-6148, USA. Email: bartolom@pennmedicine.upenn.edu

L. Narapareddy, B.A. Garcia, R.M. Schultz, and M.S. Bartolomei designed the research; L. Narapareddy, E.A. Rhon-Calderone, L.A. Vrooman, J. Baeza, Clementina Mesaros, and D.K. Nguyen performed the research; L. Narapareddy, E.A. Rhon-Calderone, L.A. Vrooman, J. Baeza D.K. Nguyen, and Y. Lan analyzed data; L. Narapareddy, R.M. Schultz, and M.S. Bartolomei wrote the manuscript.

We thank Paula Stein, Teri Ord, Monica Mainigi, and Christos Coutifaris for their technical advice with IVF procedures and helpful comments, Chris Krapp and Joanne Thorvaldsen for their technical expertise with molecular protocols. We also thank Xiaoyan Yin, Jennifer Rojas, and the Rodent Metabolic Phenotyping Core (supported in part by Penn Diabetes Research Center grant (P30-DK19525)) at the University of Pennsylvania for performing cardiometabolic assays. We acknowledge Charles-Antoine Assenmacher and the Comparative Pathology Core at the University of Pennsylvania for performing liver pathology assessment. We also thank Mary Putt for her statistical guidance and expertise.

The authors declare no competing or financial interests.

Research Funding:

This work was funded by the National Institutes of Child Health and Human Development HD092266 and HD068157 (MSB), the National Institute of General Medical Sciences GM110174 (BAG), the National Institute of Nursing Research T32NR007100 (LN), Ruth L. Kirshstein National Service Award Individual Postdoctoral Fellowship HD089623 (LAV), and the National Institute of Environmental Health Sciences P30-ES013508 (Center for Excellence in Environmental Toxicology).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biology
  • Cell Biology
  • Life Sciences & Biomedicine - Other Topics
  • assisted reproductive technologies
  • developmental origins of health and disease
  • long&#8208
  • term health
  • metabolic outcomes
  • sex&#8208
  • specific

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


Journal Title:



Volume 35, Number 4


, Pages e21523-e21523

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/rdf).
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