title: Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring.
abstract: Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10-11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Manuel
authors.initials: M
authors.lastname: Maliqueo
authors.forename: Anna
authors.initials: A
authors.lastname: Benrick
authors.forename: Julia
authors.initials: J
authors.lastname: Johansson
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.forename: Lihui
authors.initials: L
authors.lastname: Hou
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Wu
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004960:Estradiol Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D017588:Hyperandrogenism / Q000097:blood*; D007328:Insulin / Q000502:physiology; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology
chemical_list: D007328:Insulin; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D004960:Estradiol Dehydrogenases