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

Biol Reprod. 2000 Aug;63(2):457-61. doi: 10.1095/biolreprod63.2.457.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins
  • Animals
  • Collagen / pharmacology
  • Drug Interactions
  • Extracellular Matrix / physiology*
  • Female
  • Humans
  • Inhibins / pharmacology*
  • Laminin / pharmacology
  • Mice
  • Organ Culture Techniques
  • Ovarian Follicle / physiology*
  • Polylysine / pharmacology
  • Recombinant Proteins / pharmacology


  • Laminin
  • Recombinant Proteins
  • Activins
  • Polylysine
  • Inhibins
  • Collagen