Altered glucose metabolism in mouse and humans conceived by IVF.
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/m(2)/min), was lower in IVF patients (n = 14) versus control subjects (n = 20) after 3 days of an energy-balanced 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.
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Department of Obstetrics and Gynaecology, The Affiliated Hospital of Guiyang Medical College, Guiyang, People's Republic of China Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Miaoxin
M
Chen
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Linda
L
Wu
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Reproductive Medicine Center, The General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China.
Junli
J
Zhao
Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia Department of Emergency, The Affiliated Hospital of Guiyang Medical College, Guiyang, People's Republic of China.
Fang
F
Wu
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Michael J
MJ
Davies
Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Gary A
GA
Wittert
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Robert J
RJ
Norman
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Rebecca L
RL
Robker
Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia leonie.heilbronn@adelaide.edu.au.
Leonie K
LK
Heilbronn
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose