Stromelysin-3 is induced in mouse ovarian follicles undergoing hormonally controlled apoptosis, but this metalloproteinase is not required for follicular atresia

Apoptotic processes are often associated with an intense proteolytic remode ling of the extracellular matrix (ECM). Proteolytic degradation of the ECM can also be a signal that induces apoptosis. Here, we have investigated the expression pattern and functional role of the matrix metalloproteinase str omelysin-3 in follicular atresia. Twenty-four hours after the treatment of immature female mice with a low dose of eCG, both apoptosis and the stromel ysin-3 mRNA expression were suppressed approximately threefold. However, th e initial suppression of apoptosis and stromelysin-3 expression was followe d by a time-dependent increase, and 96 h after eCG treatment, the levels we re similar to those of untreated control mice. In 15- to 16-day-old juvenil e mice, the ovary consisted of relatively undeveloped follicles, and almost no apoptosis and only low stromelysin-3 mRNA expression were observed, How ever, at the age of 21 days, when several antral follicles were present, a fivefold induction in both apoptosis and stromelysin-3 mRNA expression was detected. For both models, in situ analysis revealed that the expression of stromelysin-3 mRNA was localized to the granulosa cells of atretic follicl es. To address the functional role of stromelysin-3 in follicular atresia, stromelysin-3-deficient mice were studied. However, no difference in the pa ttern of apoptotic DNA fragmentation and no apparent morphological differen ces were observed when ovaries from wild-type and stromelysin-3-deficient m ice were compared. Taken together, our data indicate that stromelysin-3 is induced during follicular atresia, but that this protease is not obligatory for initiation or completion of the atretic process.