Abstract
BackgroundThe ovulatory gonadotropin surge increases synthesis of prostaglandin E2 (PGE2) by the periovulatory follicle. PGE2 actions on granulosa cells are essential for successful ovulation. The aim of the present study is to determine if PGE2 also acts directly at the oocyte to regulate periovulatory events.MethodsOocytes were obtained from monkeys and mice after ovarian follicular stimulation and assessed for PGE2 receptor mRNA and proteins. Oocytes were cultured with vehicle or PGE2 and assessed for cAMP generation, resumption of meiosis, and in vitro fertilization.ResultsGerminal vesicle intact (GV) oocytes from both monkeys and mice expressed mRNA for the PGE2 receptors EP2, EP3, and EP4. EP2 and EP4 proteins were detected by confocal microscopy in oocytes of both species. Monkey and mouse oocytes responded to PGE2 as well as agonists selective for EP2 and EP4 receptors with elevated cAMP, consistent with previous identification of EP2 and EP4 as Gαs/adenylyl cyclase coupled receptors. Incubation of mouse GV stage oocytes with PGE2 delayed oocyte nuclear maturation in vitro, but PGE2 treatment did not alter the percentage of mouse oocytes that fertilized successfully. PGE2 treatment also decreased the percentage of monkey oocytes that resumed meiosis in vitro. In contrast with mouse oocytes, the percentage of monkey oocytes which fertilized in vitro was lower after treatment with PGE2. Monkey oocytes with intact cumulus showed delayed nuclear maturation, but fertilization rate was not affected by PGE2 treatment.ConclusionsMonkey and mouse oocytes express functional PGE2 receptors. PGE2 acts directly at mammalian oocytes to delay nuclear maturation. Surrounding cumulus cells modulate the effect of PGE2 to alter subsequent fertilization.
Highlights
The ovulatory gonadotropin surge increases synthesis of prostaglandin E2 (PGE2) by the periovulatory follicle
The present study demonstrates that mammalian oocytes express functional receptors for PGE2
These discrepancies are reminiscent of our studies of EP expression in monkey mural granulosa cells before administration of the ovulatory gonadotropin stimulus, when EP1 and EP4 mRNA were detected, but these EP proteins were not detected by immunofluorescence [8]
Summary
The ovulatory gonadotropin surge increases synthesis of prostaglandin E2 (PGE2) by the periovulatory follicle. The ovulatory surge of luteinizing hormone (LH) stimulates events within the dominant ovarian follicle which lead to ovulation. One such action of LH is to increase PGE2 levels within the follicle [1]. PGE2 stimulates ovulatory events such as expansion of cumulus granulosa cells and enhanced expression of proteases associated with follicle rupture [2]. While PGE2 acts at both cumulus and mural granulosa cells of ovulatory follicles to promote periovulatory events [10,11], comparatively little is known about the oocyte as a target for PGE2 action. A recent report suggests that mouse oocytes do not express EP receptor proteins [10]. The purpose of this study is to determine if the mammalian oocytes express EP receptors capable of signal transduction and modulation of oocyte function
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