title: Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.
abstract: Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.
authors.affiliation: Namik Kemal University, Faculty of Medicine, Department of Gynecology and Obstetrics, Tekirdag, Turkey. remziabali@yahoo.com
authors.forename: Remzi
authors.initials: R
authors.lastname: Abali
authors.forename: Mehmet Aytac
authors.initials: MA
authors.lastname: Yuksel
authors.forename: Cevat
authors.initials: C
authors.lastname: Aktas
authors.forename: Cem
authors.initials: C
authors.lastname: Celik
authors.forename: Savas
authors.initials: S
authors.lastname: Guzel
authors.forename: Gamze
authors.initials: G
authors.lastname: Erfan
authors.forename: Onder
authors.initials: O
authors.lastname: Sahin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D009866:Oogenesis / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D007641:Keratolytic Agents; D018809:Proliferating Cell Nuclear Antigen; D054304:Anti-Mullerian Hormone; D015474:Isotretinoin
keywords: anti-Müllerian hormone; apoptosis; atretic follicle; isotretinoin; ovarian reserve; toxicity