title: Interaction of extracellular matrix and activin-A in the initiation of follicle growth in the mouse ovary.
abstract: The precise mechanism for the initiation of follicle growth and progression through the earliest stages of follicle development remains largely unknown. Activins play a role during early follicle development, and evidence suggests that the extracellular matrix plays a role during later stages of follicular growth. We investigated the role of activin-A and extracellular matrix in follicle growth initiation and early follicular development in the mouse ovary. Ovaries were collected from 5-day-old mice and cultured for 10 days on polylysine, collagen, or laminin in the presence or absence of recombinant human activin-A. Follicle density, indices of follicle growth initiation (primary:primordial follicle [PY:PD] and primary:total follicle [PY:TF] ratios), ratios of multilayer follicle:total follicle (ML:TF), and follicle growth rates were compared between groups. Follicle densities were significantly higher in the extracellular matrix treatment group compared with the polylysine group (P < 0.01). Also, compared with polylysine, both collagen and laminin significantly increased indices of follicle growth initiation (PY:PD ratio: P < 0.001, odds ratio of 3.3; PY:TF ratio: P < 0.001, odds ratio of 2.5), and these were not altered by activin treatment. In the absence of activin-A, exposure to neither collagen nor laminin had an effect on multilayer follicle development. When activin-A was added, collagen and laminin had opposing effects on multilayer follicle development. Activin-A stimulated multilayer follicle development in the presence of laminin (ML:TF ratio: P = 0.01, odds ratio of 10.8), whereas it suppressed follicle growth in collagen (P = 0.01). Activin-A did not affect the ML:TF ratio in the polylysine-treated groups. These results strongly suggest that extracellular matrix components and activin-A interact with each other, and that they regulate follicle growth initiation and multilayer follicle development.
authors.affiliation: Departments of Obstetrics & Gynecology, Cornell University, Weill Medical College and New York Methodist Hospital, Brooklyn, New York 11215-9008, USA. koktay@netmail.hscbklyn.edu
authors.forename: K
authors.initials: K
authors.lastname: Oktay
authors.forename: G
authors.initials: G
authors.lastname: Karlikaya
authors.forename: O
authors.initials: O
authors.lastname: Akman
authors.forename: G K
authors.initials: GK
authors.lastname: Ojakian
authors.forename: M
authors.initials: M
authors.lastname: Oktay
mesh_terms: D028341:Activins; D000818:Animals; D003094:Collagen / Q000494:pharmacology; D004347:Drug Interactions; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000502:physiology*; D011107:Polylysine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007797:Laminin; D011994:Recombinant Proteins; D028341:Activins; D011107:Polylysine; D007265:Inhibins; D003094:Collagen