Effect of bcl-2 on the primordial follicle endowment in the mouse ovary

Effect of bcl-2 on the primordial follicle endowment in the mouse ovary
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DOI:
10.1095/biolreprod64.4.1153
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发表时间:
2001-04-01
影响因子:
3.6
通讯作者:
Furth, PA
Furth, PA
中科院分区:
生物学2区
文献类型:
--
作者:
Flaws, JA;Hirshfield, AN;Furth, PA

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关于胚胎因素在出生时调节原始卵泡天赋的大小,人们知之甚少。一些研究表明,B细胞淋巴瘤/白血病-2(BCL-2)原癌基因家族的成员可能是重要的决定因素。因此,这项研究的目的是测试bcl2是否调节出生时原始卵泡池的大小。为了验证这一假设,为了减少出生前的卵母细胞损失,我们培育了三个转基因小鼠(c-kit/bcl2小鼠),这些小鼠过表达人bcl2基因。在4.8kb的c-kit启动子的作用下,过表达针对卵巢和合适的胚胎时期。该启动子使bcl2在卵巢中的表达增加了两到三倍,而在大多数非腺组织中几乎没有过表达。在出生后第8-60天,从c-kit/bcl2纯合子和非转基因窝产仔(对照组)采集卵巢,进行卵泡数量的组织学评估。所有c-kit/bcl2系小鼠出生时原始卵泡数量均显著多于对照组(P<0.05)。然而,到出生后30-60天,c-kit/bcl2组小鼠的卵泡数量与对照组没有显著差异。这些结果表明,bcl2的过度表达增加了出生时原始卵泡的数量,但原始卵泡的过剩在出生后并不保持。这些数据表明,卵巢可能包含一种普查机制,通过这种机制,出生时过多的原始卵泡被检测出来,并在成年后从卵巢中移除。
Little is known about the embryonic factors that regulate the size of the primordial follicle endowment at birth. A few studies suggest that members of the B-cell lymphoma/leukemia-2 (bcl-2) family of protooncogenes may be important determinants. Thus, the purpose of this study was to test whether bcl-2 regulates the size of the primordial follicle pool at birth. To test this hypothesis, three lines of transgenic mice (c-kit/bcl-2 mice) were generated that overexpress human bcl-2 in an effort to reduce prenatal oocyte loss. The overexpression was targeted to the ovary and appropriate embryonic time period with the use of a 4.8-kilobase c-kit promoter. This promoter provided two to three times more expression of bcl-2 in the ovaries with minimal or no overexpression in most nongonadal tissues. On Postnatal Days 8-60, ovaries were collected from homozygous c-kit/bcl-2 and nontransgenic littermates (controls) and processed for histological evaluation of follicle numbers. All lines of c-kit/bcl-2 mice were born with significantly more primordial follicles than control mice (P less than or equal to 0.05). By Postnatal Days 30-60, however, there were no significant differences in follicle numbers between c-kit/bcl-2 and control mice. These results indicate that bcl-2 overexpression increases the number of primordial follicles at birth, but that the surfeit of primordial follicles is not maintained in postnatal life. These data suggest that it is possible that the ovary may contain a census mechanism by which excess numbers of primordial follicles at birth are detected and removed from the ovary by adulthood.