title: Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels.
abstract: Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome.
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil. Electronic address: marcondes_rr@hotmail.com.
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Marcondes
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: Kátia C
authors.initials: KC
authors.lastname: Carvalho
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Duarte
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Garcia
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: Vinícius C
authors.initials: VC
authors.lastname: Amaral
authors.affiliation: Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, Universidade Federal de São Paulo, 04023900 São Paulo, Brazil.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Simões
authors.affiliation: Departamento de Cirurgia, Disciplina de Urologia, Setor de Reprodução Humana, Universidade Federal de São Paulo, 04024002 São Paulo, Brazil.
authors.forename: Edson G
authors.initials: EG
authors.lastname: Lo Turco
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: José M
authors.initials: JM
authors.lastname: Soares
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Baracat
authors.affiliation: Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, 01246903 São Paulo, Brazil. Electronic address: garmaciel@gmail.com.
authors.forename: Gustavo A R
authors.initials: GA
authors.lastname: Maciel
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood*; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: 17-Alpha-hydroxylase; Animal models; LH receptor; Polycystic ovary syndrome; Steroid