Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring.
Associations between maternal obesity and adverse fetal outcomes are well documented, but the mechanisms involved are largely unknown. Most previous work has focused on postconceptional events, however, our laboratory has shown pre- and periconceptional aberrations in maternal glucose metabolism have adverse effects on oocytes and embryos that carry on to the fetus. To demonstrate effects of maternal obesity in the pre- and periconceptional periods, we compared reproductive tissues from diet-induced obese female mice to those of control mice. Ovaries were either stained for follicular apoptosis or dissected and evaluated for oocyte size and meiotic maturation. Mice were also mated and followed for reproductive outcomes including preimplantation embryonic IGF-I receptor (IGF-IR) immunostaining, midgestation fetal growth, and midgestational placental IGF receptor 2 (Igf2r) mRNA. Delivered pups were followed for growth and development of markers of metabolic syndrome. Compared with controls, obese mice had significantly more apoptotic ovarian follicles, smaller and fewer mature oocytes, decreased embryonic IGF-IR staining, smaller fetuses, increased placental Igf2r mRNA, and smaller pups. All weaned pups were fed a regular diet. At 13 wk pups delivered from obese mice were significantly larger, and these pups demonstrated glucose intolerance and increased cholesterol and body fat suggesting early development of a metabolic-type syndrome. Together, our findings suggest maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stage and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception.
Jungheim
Emily S
ES
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Schoeller
Erica L
EL
Marquard
Kerri L
KL
Louden
Erica D
ED
Schaffer
Jean E
JE
Moley
Kelle H
KH
D000818:Animals; D000831:Animals, Newborn; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006130:Growth Disorders / Q000209:etiology* / Q000473:pathology; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D009865:Oocytes / Q000473:pathology*; D010053:Ovary / Q000002:abnormalities* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology
D004041:Dietary Fats