Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad.

Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad.
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DOI:
10.1210/endo.136.8.7628407
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发表时间:
1995-08
期刊:
影响因子:
4.8
通讯作者:
V. Ratts;Jodi A. Flaws;Rebecca Kolp;C. Sorenson;Jonathan L. Tilly
V. Ratts;Jodi A. Flaws;Rebecca Kolp;C. Sorenson;Jonathan L. Tilly
中科院分区:
医学2区
文献类型:
--
作者:
V. Ratts;Jodi A. Flaws;Rebecca Kolp;C. Sorenson;Jonathan L. Tilly

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卵母细胞损失,无论是直接通过损耗(生殖细胞死亡)还是间接通过卵泡闭锁(体细胞或颗粒细胞死亡),都是与确定女性正常或过早生殖衰老时间相关的基本事件。虽然细胞凋亡已被报道为卵巢生殖细胞和体细胞死亡的潜在机制,但导致卵巢细胞死亡的最终分子步骤尚未完全阐明。为了检验bcl-2基因产物的死亡抑制活性是否对生殖细胞存活很重要,我们使用bcl-2功能丧失(bcl-2 -/-)转基因小鼠模型进行研究。组织学分析显示,从bcl-2 -/-小鼠收集的卵巢具有许多异常形成的原始卵泡样结构,其中含有单层颗粒细胞,没有卵母细胞。此外,与杂合子(bcl-2 -/+)或野生型(bcl-2 +/+)小鼠相比,bcl-2 -/-小鼠中含有健康卵母细胞的原始卵泡总数明显减少,这表明bcl-2死亡抑制基因的表达对于哺乳动物卵巢中生殖细胞和原始卵泡的正常补体供体至关重要。
Oocyte loss, either directly through attrition (germ cell death) or indirectly through follicular atresia (somatic or granulosa cell death), is a fundamental event associated with defining the time of normal or premature reproductive senescence in females. Although apoptosis has been reported to function as the underlying mechanism responsible for death of both germ cells and somatic cells in the ovary, the final molecular steps which commit ovarian cells to death have not been fully elucidated. To examine if death repressor activity of the bcl-2 gene product is important for germ cell survival, we conducted studies using a Bcl-2 loss-of-function (bcl-2 -/-) transgenic mouse model. Histological analyses revealed that ovaries collected from bcl-2 -/- mice possessed numerous aberrantly formed primordial follicle-like structures containing a single layer of granulosa cells without an oocyte. Additionally, the total number of primordial follicles present which contained a healthy oocyte was markedly reduced in bcl-2 -/- mice as compared to heterozygote (bcl-2 -/+) or wild-type (bcl-2 +/+) mice, suggesting that expression of the bcl-2 death repressor gene is critical for endowment of a normal complement of germ cells and primordial follicles in the mammalian ovary.