the newly formed corpus luteum, and VEGF protein is localized in steroidogenic cells of the corpus luteum. Autocrine or paracrine effects of order Enzalutamide luteal prostaglandins may be involved in the control of the corpus luteum lifespan and functions. Our previous study demonstrated that cyclooxygenase 2 activity may be important for angiogenesis in the early developing corpus luteum in rats. When gonadotropinprimed rats were injected with a COX 2 inhibitor, NS 398, for 2 days after ovulation, serum progesterone levels decreased together with vasculature impairment in the developing corpus luteum. VEGF stimulates the expressions of COX 2 and prostaglandin E synthase mRNAs in rat luteal cells. Thus, COX 2 may be involved in the physiological angiogenesis of the corpus luteum that takes place during the early luteal phase in rats.
To address the role of eicosanoids in luteal angiogenesis in the present study, we examined the effects of exogenous PGE2, Ciprostene, and U 46619 on progesterone secretion and angiogenesis Gene expression using the gonadotropin induced ovulation model in rats. We also examined the possible role of eicosanoids in VEGFinduced ovarian angiogenesis. Immature Wistar?Imamichi rats were maintained in an air conditioned room under controlled lighting with free access to food and water. All experimental protocols with rats used in this study were reviewed and approved by the Institutional Animal Care Committees at the Tokyo University of Pharmacy and Life Science, in compliance with institutional guidelines for experimental animal care.
Pseudopregnancy was induced by high dose gonadotropin, equine chorionic gonadotropin, and human Anastrozole molecular weight CG administered 54 h after eCG treatment. Gonadotropin primed rats were injected with NS 398, a selective COX 2 inhibitor, at 0900 h on the day of ovulation and the following day. The dose of NS 398 sufficient to inhibit COX activity was determined in our previous study. At 1200 h on day 26, rats were anesthetized with ether, the uterus was exposed, the middle of the uterine horn was ligated, and the ovary on the side opposite of where the injection would occur was removed. PGE2, Ciprostene, or U 46619 was injected into the ligated uterine lumen near the ovary. The doses of eicosanoids used were determined based upon the physiological contents in the preovulatory ovary reported by Brown and Poyser.
The mixture of these three eicosanoids was also administered as a treatment. Animals in the control group were injected with the same amount of PBS containing 0. 15% gelatin as a vehicle.