Gelatinase A and membrane-type matrix metalloproteinases 1 and 2 are responsible for follicle rupture during ovulation in the medaka

doi:10.1073/pnas.0502423102

Gelatinase A and membrane-type matrix metalloproteinases 1 and 2 are responsible for follicle rupture during ovulation in the medaka

^*Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan; and ^†Amato Pharmaceutical Products, Fukuchiyama, Kyoto 620-0932, Japan

Edited by Ryuzo Yanagimachi, University of Hawaii, Honolulu, HI (received for review March 24, 2005)

Abstract

Identification of the hydrolytic enzymes involved in follicle rupture during vertebrate ovulation remains a central challenge for research in reproductive biology. Here, we report a previously uncharacterized approach to this problem by using an in vitro ovulation system in the medaka, Oryzias latipes, which is a small freshwater teleost. We found that follicle rupture in the medaka ovary involves the cooperation of at least three matrix metalloproteinases (MMPs), together with the tissue inhibitor of metalloproteinase-2b protein. We determined the discrete roles of each of these proteins during follicle rupture. Our results indicated that gelatinase A induces the hydrolysis of type IV collagen constituting the basement membrane, membrane-type 2 MMP degrades type I collagen present in the theca cell layer, and MT1-MMP and the tissue inhibitor of metalloproteinase-2b are involved in the production and regulation of gelatinase A. These findings will help clarify the mechanism of follicle wall degradation during ovulation in mammalian species.

medaka fish

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: ttakaha{at}sci.hokudai.ac.jp.
Author contributions: K.O., M.M., and T.T. designed research; K.O., N.T., and M.S. performed research; K.O., N.T., M.S., M.M., and T.T. analyzed data; and T.T. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: APMA, p-aminophenylmercuric acetate; MMP, matrix metalloproteinase; MT, membrane-type; TIMP, tissue inhibitor of metalloproteinase.
Data deposition: The sequences reported in this paper have been deposited in the DNA Data Bank of Japan database (accession nos. AB185847, AB072928, AB072929, AB185849, AB193468, and AB193469).