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自然抑制的细胞凋亡可防止成年大毛丝鼠(啮齿目,豚鼠形亚目)卵巢中的卵泡闭锁和卵母细胞储备减少。

Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve decline in the adult ovary of Lagostomus maximus (Rodentia, Caviomorpha).

作者信息

Jensen Federico, Willis Miguel A, Albamonte Mirta S, Espinosa María B, Vitullo Alfredo D

机构信息

Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico, CEBBAD, Universidad Maimónides, Hidalgo 775, C1405BCK Buenos Aires, Argentina.

出版信息

Reproduction. 2006 Aug;132(2):301-8. doi: 10.1530/rep.1.01054.

Abstract

It has been widely accepted that mammalian females are born with a non-renewing, finite pool of oocytes that will be continuously cleared by atresia, with only a small proportion of them reaching ovulation. Apoptosis regulates this mass germ cell death, especially through the balance between pro- and anti-apoptotic proteins encoded by the BCL-2 gene family. The caviomorph rodent Lagostomus maximus, the South American plains viscacha, displays the highest ovulation rate known for a mammal releasing 400-800 eggs per cycle. We tested the hypothesis that in L. maximus massive polyovulation is a consequence of reduced apoptosis resulting in suppressed follicular atresia. We found that anti-apoptotic BCL-2 gene is markedly expressed in all kind of follicles from primordial to fully mature antral stages in the adult ovary of L. maximus. On the other hand, pro-apoptotic BAX gene showed weak signals or was undetectable by immunohistochemical examination. Western blot against both proteins confirmed immunohistochemical results. Screening for DNA fragmentation by TUNEL assay was conspicuously negative in ovaries from both pregnant and non-pregnant females. In addition, alpha-oestrogen receptor also showed an enhanced expression from primordial stage to fully mature antral follicles. Our results show that natural preferential expression of BCL-2 and restricted BAX expression greatly suppresses apoptosis in the ovary of L. maximus. This prevents the decline of the oocyte reserve by abolishing follicular atresia and enables the highest ovulation rate known for a mammal, 400-800 or more eggs per cycle.

摘要

哺乳动物雌性个体出生时具有不可更新的有限卵母细胞库,这些卵母细胞会不断因闭锁而被清除,只有一小部分能够排卵,这一观点已被广泛接受。细胞凋亡调节着这种大量生殖细胞的死亡,特别是通过BCL - 2基因家族编码的促凋亡蛋白和抗凋亡蛋白之间的平衡来实现。豚鼠形啮齿动物南美草原原鼠(Lagostomus maximus)每个周期能排出400 - 800枚卵,是已知排卵率最高的哺乳动物。我们验证了这样一个假说:在南美草原原鼠中,大量排卵是细胞凋亡减少导致卵泡闭锁受抑制的结果。我们发现,抗凋亡的BCL - 2基因在南美草原原鼠成年卵巢中从原始卵泡到完全成熟的窦状卵泡的所有卵泡类型中均有显著表达。另一方面,促凋亡的BAX基因通过免疫组织化学检测显示信号较弱或无法检测到。针对这两种蛋白的蛋白质印迹法证实了免疫组织化学结果。通过TUNEL检测筛选DNA片段化,结果显示怀孕和未怀孕雌性的卵巢均明显呈阴性。此外,α - 雌激素受体从原始卵泡阶段到完全成熟的窦状卵泡也呈现出表达增强的现象。我们的研究结果表明,BCL - 2的自然优先表达和BAX表达受限极大地抑制了南美草原原鼠卵巢中的细胞凋亡。这通过消除卵泡闭锁防止了卵母细胞储备的减少,并使得南美草原原鼠能够拥有已知哺乳动物中最高的排卵率,即每个周期排卵400 - 800枚或更多。

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