Altered glucose metabolism in mouse and humans conceived by IVF

Miaoxin Chen, Linda Wu, Junli Zhao, Fang Wu, Michael J. Davies, Gary A. Wittert, Robert J. Norman, Rebecca L. Robker, Leonie K. Heilbronn

Research output: Contribution to journalArticleResearchpeer-review

69 Citations (Scopus)

Abstract

In vitro fertilization (IVF) may influence the metabolic health of children. However, in humans, it is difficult to separate out the relative contributions of genetics, environment, or the process of IVF, which includes ovarian stimulation (OS) and embryo culture. Therefore, we examined glucose metabolism in young adult humans and in adult male C57BL/6J mice conceived by IVF versus natural birth under energy-balanced and high-fat-overfeeding conditions. In humans, peripheral insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp (80 mU/m2/min), was lower in IVF patients (n = 14) versus control subjects (n = 20) after 3 days of an energybalanced diet (30% fat). In response to 3 days of overfeeding (+1,250 kcal/day, 45% fat), there was a greater increase in systolic blood pressure in IVF versus controls (P = 0.02). Mice conceived after either OS alone or IVF weighed significantly less at birth versus controls (P < 0.01). However, only mice conceived by IVF displayed increased fasting glucose levels, impaired glucose tolerance, and reduced insulin-stimulated Akt phosphorylation in the liver after 8 weeks of consuming either a chow or high-fat diet (60% fat). Thus, OS impaired fetal growth in the mouse, but only embryo culture resulted in changes in glucose metabolism that may increase the risk of the development of metabolic diseases later in life, in both mice and humans. Readers may use this article as long as the work is properly cited , the use is educational and not for profit , and the work is not altered.

Original languageEnglish
Pages (from-to)3189-3198
Number of pages10
JournalDiabetes
Volume63
Issue number10
DOIs
Publication statusPublished - Oct 2014

Cite this