Follicular development is impaired by inhibitors of serine proteases in the rat.
Serine proteases such as plasminogen activators are produced by granulosa cells both in vivo and in vitro and have been implicated in the process of ovulation. For a study of potential roles of serine proteases in early follicular development, immature rats were injected with pregnant mare serum gonadotropin, followed 2 hours later by laparotomy and injection of the serine protease inhibitors benzamidine and epsilon-aminocaproic acid into the bursa of one ovary. As a control, saline solution was injected into the contralateral bursa. Animals were put to death 48 hours after injection of serine protease inhibitors, and three to five randomly selected longitudinal sections were evaluated by computerized morphometry. The area occupied by antral follicles relative to the total cross-sectional area of each section was computed. Resultant ratios from serine protease inhibitor-treated ovaries were compared with those from contralateral control ovaries. Ninety-three percent of serine protease inhibitor-treated ovaries showed a reduction in antral follicular size when compared with corresponding control ovaries, which is indicative of inhibitory effects of serine protease inhibitor treatment on folliculogenesis. To further investigate this effect, ovulation was induced by human chorionic gonadotropin administration 48 hours after pregnant mare serum gonadotropin and 46 hours after serine protease inhibitor or saline solution treatment. Animals were put to death 20 hours later and the number of oocytes ovulated into oviducts was determined. Oviducts from serine protease inhibitor-treated ovaries contained 51% fewer oocytes than their control counterparts. Artifacts of surgical stress or vascular diffusion of serine protease inhibitor from treated to control sides were ruled out by appropriate control experiments. We conclude that early serine protease inhibitor treatment of pregnant mare serum gonadotropin-stimulated rat ovaries impairs folliculogenesis. Thus, in addition to involvement in ovulation, serine proteases appear to play important roles throughout follicular development.
Pellicer
A
A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
Lightman
A
A
Ariza
A
A
DeCherney
A H
AH
Naftolin
F
F
Littlefield
B A
BA
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D010960:Plasminogen Activators / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors
D001550:Benzamidines; D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D015842:Serine Proteinase Inhibitors; D010960:Plasminogen Activators; C032157:benzamidine; D015119:Aminocaproic Acid