title: Effects of recombinant activin A on in vitro culture of mouse preantral follicles.
abstract: Activins are part of the intragonadal factors that can modulate the actions of gonadotropins and regulate cellular functions during preantral or early antral stages of folliculogenesis in vivo. In a mouse early preantral follicle culture system, activin A production was measured and recombinant bovine activin A (r-ACT A) was added (10 or 50 ng/ml) to recombinant follicle-stimulating hormone (r-FSH)-supplemented (10 or 100 mIU/ml) medium for a 12-day culture period. Specificity of activin A action was ascertained by addition of recombinant human follistatin (r-FA; 20 or 100 ng/ml). Immunoreactive activin A concentrations in mouse follicle-conditioned medium increased by a factor of 20-50, reaching concentrations from 2 to 5 ng/ml at end of culture. In the initial days of culture, additions of r-ACT A to r-FSH-supplemented medium provoked a dramatic volumetric increase and earlier attachment of the follicle. A dose of 100 ng/ml r-FS was able to block the actions of 10 ng/ml but not those caused by 50 ng/ml r-ACT A. In follicle cultures supplemented with 10 mIU/ml r-FSH, additions of r-ACT induced a dose-dependent inhibin (INH) and estradiol (E2) increase. Basal and human chorionic gonadotropin (HCG)-induced progesterone (P) production were not influenced by r-ACT A or r-FS additions. Addition of r-ACT A decreased (P = 0.017) the intact follicle survival rate and had no influence on final oocyte diameter. In cultures supplemented by 10 mIU/ml r-FSH, additions of r-ACT A did not influence progression and resumption of meiosis I. Use of a higher r-FSH supplementation dose (100 mIU/ml) tended to affect meiosis I adversely (P = 0.052), and r-ACT A addition amplified this effect significantly (P = 0.007). These in vitro experiments demonstrate pronounced effects from r-ACT on r-FSH-mediated follicle survival, growth, and estrogen biosynthesis.
authors.affiliation: Centre for Reproductive Medicine, University Hospital and Medical School, Brussels Free University, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Smitz
authors.forename: R
authors.initials: R
authors.lastname: Cortvrindt
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: H
authors.initials: H
authors.lastname: Vanderstichele
mesh_terms: D028341:Activins; D000818:Animals; D002417:Cattle; D002455:Cell Division; D006063:Chorionic Gonadotropin; D046508:Culture Techniques; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development; D010053:Ovary; D011374:Progesterone / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D006063:Chorionic Gonadotropin; D006133:Growth Substances; D011994:Recombinant Proteins; D028341:Activins; D011374:Progesterone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone