Interaction of extracellular matrix and activin-A in the initiation of follicle growth in the mouse ovary

The precise mechanism for the initiation of follicle growth and progression through the earliest stages of follicle development remains largely unknow n. Activins play a role during early follicle development, and evidence sug gests that the extracellular matrix plays a role during later stages of fol licular growth. We investigated the role of activin-A and extracellular mat rix in follicle growth initiation and early follicular development in the m ouse ovary. Ovaries were collected from Ei-day-old mice and cultured for 10 days on polylysine, collagen, or laminin in the presence or absence of rec ombinant human activin-A. Follicle density, indices of follicle growth init iation (primary:primordial follicle [PY:PD] and primary:total follicle [PY: TF] ratios), ratios of multilayer follicle:total follicle (ML:TF), and foll icle growth rates were compared between groups. Follicle densities were sig nificantly higher in the extracellular matrix treatment group compared with the polylysine group (P < 0.01). Also, compared with polylysine, both coll agen and laminin significantly increased indices of follicle growth initiat ion (PY:PD ratio: P < 0.001, odds ratio of 3.3; PY:TF ratio: P < 0.001, odd s ratio of 2.5), and these were not altered by activin treatment. In the ab sence 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:T F ratio: P = 0.01, odds ratio of 10.8), whereas it suppressed follicle grow th in collagen (P = 0.01). Activin-A did not affect the ML:TF ratio in the polylysine-treated groups. These results strongly suggest that extracellula r matrix components and activin-A interact with each other, and that they r egulate follicle growth initiation and multilayer follicle development.