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a Departments of Obstetrics & Gynecology, Cornell University, Weill Medical College and New York Methodist Hospital, Brooklyn, New York 11215-9008
b Department of Anatomy & Cell Biology, State University of New York HSC, Brooklyn, New York 11203
c Memorial Sloan-Kettering Cancer Center Research Laboratories, New York, New York 10021
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.
First decision: 22 December 1999.
1 Supported by the ASRM-Mead Johnson and ASRM-Serono Research Grants.
2 Correspondence: Kutluk Oktay, Department of Obstetrics & Gynecology, Cornell University, Weill Medical College and New York Methodist Hospital, 506 Sixth Street, Brooklyn, NY 11215-9008. FAX: 718 780 3079; koktay{at}netmail.hscbklyn.edu
3 Current address: Department of Pathology, Yale University Medical School, New Haven, CT.
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