title: Antiandrogen flutamide affects folliculogenesis during fetal development in pigs.
abstract: Androgen deficiency during prenatal development may affect the expression of genes involved in the folliculogenesis regulation. In order to study the effect of antiandrogen on fetal ovarian development, pregnant gilts were injected with flutamide (for 7 days, 50 mg/kg bodyweight per day) or corn oil (control groups) starting on gestation days 43 (GD50), 83 (GD90), or 101 (GD108). The obtained fetal ovaries were fixed for histology and immunohistochemistry or frozen for real-time PCR. Morphological evaluation, TUNEL assay, and expression of selected factors (Ki-67, GATA binding transcription factor 4 (GATA4), E-Cadherin and tumor necrosis factor a (TNFa)) were performed. On GD90 and GD108, ovaries following flutamide administration showed a higher number of egg nests and lower number off ollicles than those in respective control groups. An increased mRNA and protein expression of Ki-67 was observed in flutamide-treated groups compared with controls on GD50 and GD108 but decreased expression was found on GD90. In comparison to control groups a higher percentage of TUNEL-positive cells was shown after flutamide exposure on GD50 and GD90 and a lower percentage of apoptotic cells was observed on GD108. These data were consistent with changes in TNF (TNFa) mRNA expression, which increased on GD90 and decreased on GD108. E-cadherin mRNA and protein expression was upregulated on GD50 and downregulated on GD90 and GD108. In conclusion diminished androgen action in porcine fetal ovaries during mid- and late gestation leads to changes in the expression of genes crucial for follicle formation. Consequently, delayed folliculogenesis was observed on GD90 and GD108. It seems however that androgens exhibit diverse biological effects depending on the gestational period.
authors.affiliation: Department of Endocrinology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Knapczyk-Stwora
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Durlej-Grzesiak
authors.forename: Renata E
authors.initials: RE
authors.lastname: Ciereszko
authors.forename: Marek
authors.initials: M
authors.lastname: Koziorowski
authors.forename: Maria
authors.initials: M
authors.lastname: Slomczynska
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007279:Injections, Subcutaneous; D019394:Ki-67 Antigen / Q000235:genetics; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D015820:Cadherins; D050991:GATA4 Transcription Factor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005485:Flutamide