title: Disorders of follicle development and steroidogenesis in ovaries of androgenised foetal sheep.
abstract: The prenatally androgenised (PA) sheep is a well-recognised model for the study of developmental programming of adult polycystic ovary syndrome (PCOS). Most of the studies to date have involved examination of the reproductive and metabolic effects in the offspring after puberty, but more recently, it has been reported that there is disruption of follicle formation and steroid gene expression in ovaries of foetal sheep after exposure of the mother to excess androgen. Our study examines evidence for precocious primordial follicle formation at day 90 of gestation in ovaries of foetal Poll Dorset sheep. Using a specific marker of germ cells (VASA homologue protein) in ovarian sections, we found that androgenised sheep had nearly double the proportion of germ cells enclosed in follicles compared with control animals. When analysed by follicle stage, there was no significant difference between groups in the proportion of primordial follicles and growing (transitional and primary) follicles. Differences between PA and control foetal sheep were found in both mRNA and in protein expression of steroidogenic enzymes and androgen receptor. Our results in Dorset ewes are complementary to previous reports, but suggest that the timing of follicle formation and steroidogenic activity may vary between different breeds as well as in response to androgen. These data show that granulosa cells constitute a specific target for programming by androgen in utero and raise key questions about the role of exposure to androgen in utero in developmental origins of PCOS.
authors: Imperial College LondonInstitute of Reproductive and Developmental Biology, London W12 0NN, UKInstitute of BiodiversityAnimal Health and Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK.
authors: Fabio V
authors: FV
authors: Comim
authors: Imperial College LondonInstitute of Reproductive and Developmental Biology, London W12 0NN, UKInstitute of BiodiversityAnimal Health and Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK.
authors: Kate
authors: K
authors: Hardy
authors: Imperial College LondonInstitute of Reproductive and Developmental Biology, London W12 0NN, UKInstitute of BiodiversityAnimal Health and Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK.
authors: Jane
authors: J
authors: Robinson
authors: Imperial College LondonInstitute of Reproductive and Developmental Biology, London W12 0NN, UKInstitute of BiodiversityAnimal Health and Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK s.franks@imperial.ac.uk.
authors: Stephen
authors: S
authors: Franks
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D012756:Sheep / Q000196:embryology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D043343:Testosterone Propionate / Q000494:pharmacology*; D014770:Virilism
chemical_list: D013256:Steroids; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D043343:Testosterone Propionate
keywords: PCOS; VASA; follicular development; prenatal androgenisation