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BOR - Papers in Press, published online ahead of print April 30, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.065326
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Submitted October 1, 2007
Returned for revision November 5, 2007
Accepted April 21, 2008

Ovary


The Ovary of the Gestating South American Plains Vizcacha (Lagostomus maximus): Suppressed Apoptosis and Corpora Lutea Persistence

Federico Jensen , Miguel A. Willis , Noelia P. Leopardo , María B. Espinosa , and Alfredo D. Vitullo *

* To whom correspondence should be addressed. E-mail: vitullo.alfredo{at}maimonides.edu.

Abstract
The South American plains vizcacha, L. maximus, displays an exceptional ovulation rate of up to 800 eggs per cycle, the highest rate recorded for a mammal. Massive polyovulation arises from the over-expression of the apoptosis-inhibiting BCL2 gene leading to a suppression of apoptotic pathways responsible for follicular atresia in mammals. We analyzed the ovarian histology, ovarian apoptosis and apoptosis-related protein expression with special emphasis in corpora lutea throughout the 5-month long gestation period, at parturition day and early post-partum in L. maximus. Corpora lutea were abundant throughout gestation with no sign of structural regression even at the end of gestation. Both immunohistochemistry and western blot analysis showed strong signals for apoptosis-inhibiting BCL2 protein whereas the pro-apoptotic BAX protein was just detected in isolated luteal cells in gestating females and post-partum females. Apoptosis-associated DNA fragmentation detected by TUNEL was very scarce and occasional, and correlated with BAX detection in luteal cells. Marked expression of progesterone and alpha-estrogen receptors in luteal cells was found at early-, mid- and late-gestation, as well as at parturition day and early post-partum samples. Additionally, serum level of progesterone increased markedly to reach maximal values at late gestation and decreasing at parturition to levels found at early gestation, suggesting that corpora lutea remained functional throughout gestation. These results point out that the unusual ovarian environment of L. maximus in which germ cell demise is abolished through anti-apoptotic BCL2 gene over-expression also preserves structural integrity and functionality of corpora lutea during the whole gestation. Over expression of anti-apoptotic BCL2 gene may represent a strategy for an essential need of ovary and corpora lutea in order to maintain pregnancy until term.

Key words: Ovary • Apoptosis • Corpus luteum • Progesterone • Progesterone receptor





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