Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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BOR - Papers in Press, published online ahead of print February 19, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.013755
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BIOLOGY OF REPRODUCTION 69, 99–105 (2003)
DOI: 10.1095/biolreprod.102.013755
© 2003 by the Society for the Study of Reproduction, Inc.


Ovary

Differential Effects of RU486 and Indomethacin on Follicle Rupture During the Ovulatory Process in the Rat1

Francisco Gaytán2,3, Carmen Bellido3, María Gaytán3, Concepción Morales4, and José Eugenio Sánchez-Criado3

Department of Cell Biology, Physiology and Immunology3 Department of Pathology,4 School of Medicine, University of Cordoba, Spain

Ovulation (i.e., the release of mature oocytes from the ovary) requires spatially targeted follicle rupture at the apex. Both progesterone and prostaglandins play key roles in the ovulatory process. We have studied follicle rupture and ovulation in adult cycling rats treated with a progesterone receptor antagonist (RU486), an inhibitor of prostaglandin synthesis (indomethacin, IM), or both. All rats were treated with LHRH antagonist on the morning (0900 h) of proestrus to inhibit endogenous gonadotropins and with 10 µg of ovine LH (oLH) at 1700 h in proestrus to induce ovulation. Animals were treated from metestrus to proestrus with 2 mg/day of RU486 or vehicle (olive oil) and on the morning of proestrus (1200 h) with 1 mg of IM or vehicle (olive oil). Some rats treated with vehicle or RU486 were killed on the morning of proestrus to assess preovulatory follicle development. The remaining rats were killed on the morning of estrus to study follicle rupture and ovulation. In vehicle-treated rats, oLH induced ovulation in 98% of follicles. In IM-treated rats, spatial targeting of follicle rupture was disrupted. Most oocytes were released to the ovarian interstitium (50%) or to the periovarian space (39%), and a smaller percentage (11%) of oocytes remained trapped inside the luteinized follicle. RU486-treated rats showed, on the morning of estrus, unruptured luteinized follicles. Only occasionally (2.8%), the oocytes were released to the periovarian space. IM treatment induced follicle rupture in RU486-treated rats, and 25% of oocytes were released to the ovarian interstitium. However, the number of oocytes released to the periovarian space (i.e., ovulated) was not increased by IM treatment in rats lacking progesterone actions. Overall, these data indicate that RU486 and IM have opposite effects on follicle rupture and suggest that both progesterone and prostaglandins are necessary for the spatial targeting of follicle rupture at the apex.

1 This work has been subsidized by Grant BFI2002-00485 from the DGI, Spain.

2 Correspondence: F. Gaytán, Department of Cell Biology, Physiology and Immunology, School of Medicine, University of Cordoba, 14004-Cordoba, Spain. FAX: 57 34 218288; bc1galuf{at}uco.es







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Copyright © 2003 by the Society for the Study of Reproduction.