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妊娠期南美草原原鼠(Lagostomus maximus)的卵巢:凋亡抑制与黄体持续存在。

The ovary of the gestating South American plains vizcacha (Lagostomus maximus): suppressed apoptosis and corpora lutea persistence.

作者信息

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

机构信息

Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico, CEBBAD, Universidad Maimónides, C1405BCK Buenos Aires, Argentina.

出版信息

Biol Reprod. 2008 Aug;79(2):240-6. doi: 10.1095/biolreprod.107.065326. Epub 2008 Apr 30.

Abstract

The South American plains vizcacha, Lagostomus 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 overexpression 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-mo-long gestation period, at parturition day and early postpartum, 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 proapoptotic BAX protein was just detected in isolated luteal cells in gestating females and postpartum 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 postpartum 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 antiapoptotic BCL2 gene overexpression also preserves structural integrity and functionality of corpora lutea during the whole gestation. Overexpression of antiapoptotic BCL2 gene may represent a strategy for an essential need of ovary and corpora lutea in order to maintain pregnancy until term.

摘要

南美草原鼠兔(Lagostomus maximus)每个周期的排卵率高达800枚卵,堪称异常之高,是哺乳动物中记录到的最高排卵率。大量排卵源于抗凋亡BCL2基因的过度表达,导致负责哺乳动物卵泡闭锁的凋亡途径受到抑制。我们分析了南美草原鼠兔在长达5个月的妊娠期、分娩日和产后早期整个过程中的卵巢组织学、卵巢凋亡以及凋亡相关蛋白表达,特别关注黄体情况。整个妊娠期黄体丰富,即使在妊娠末期也没有结构退化的迹象。免疫组织化学和蛋白质印迹分析均显示抗凋亡BCL2蛋白有强烈信号,而促凋亡BAX蛋白仅在妊娠雌性和产后雌性的孤立黄体细胞中检测到。通过TUNEL检测到的凋亡相关DNA片段非常稀少且偶然,并且与黄体细胞中BAX的检测相关。在妊娠早期、中期和晚期以及分娩日和产后早期样本中,黄体细胞中均发现孕酮和α-雌激素受体有明显表达。此外,孕酮的血清水平在妊娠晚期显著升高至最大值,在分娩时下降至妊娠早期的水平,这表明黄体在整个妊娠期都保持功能。这些结果表明,南美草原鼠兔异常的卵巢环境通过抗凋亡BCL2基因的过度表达消除了生殖细胞死亡,在整个妊娠期也保持了黄体的结构完整性和功能。抗凋亡BCL2基因的过度表达可能代表了卵巢和黄体为维持妊娠至足月的基本需求而采取的一种策略。

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