title: In utero betamethasone affects 3β-hydroxysteroid dehydrogenase and inhibin-α immunoexpression during testis development.
abstract: Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: G
authors.identifier: 0000-0002-4955-6873
authors.initials: G
authors.lastname: Pedrana
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: H
authors.initials: H
authors.lastname: Viotti
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: P
authors.initials: P
authors.lastname: Lombide
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: G
authors.initials: G
authors.lastname: Sanguinetti
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: C
authors.initials: C
authors.lastname: Pino
authors.affiliation: 1Departmento de Morfología y Desarrollo,Facultad de Veterinaria,Universidad de la República Oriental del Uruguay,Uruguay.
authors.forename: D
authors.identifier: 0000-0002-8367-7142
authors.initials: D
authors.lastname: Cavestany
authors.affiliation: 2Departments of Biochemistry and Biomedical Sciences, Obstetrics and Gynecology,Pediatrics and the Farncombe Digestive Diseases Institute,McMaster University,Hamilton,Canada.
authors.forename: D M
authors.initials: DM
authors.lastname: Sloboda
authors.affiliation: 3UWA School of Animal Biology M092,University of Western Australia,Crawley,Australia.
authors.forename: G B
authors.identifier: 0000-0002-1905-7934
authors.initials: GB
authors.lastname: Martin
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005865:Gestational Age; D007124:Immunoenzyme Techniques; D007265:Inhibins / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012756:Sheep; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
chemical_list: C094377:inhibin-alpha subunit; D007265:Inhibins; D001623:Betamethasone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: fetus; glucocorticoid; male; programming; reproduction