Flaws J A, Hirshfield A N, Hewitt J A, Babus J K, Furth P A
Departments of Epidemiology/Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Biol Reprod. 2001 Apr;64(4):1153-9. doi: 10.1095/biolreprod64.4.1153.
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 < or = 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.
关于调节出生时原始卵泡储备大小的胚胎因素，人们所知甚少。一些研究表明，原癌基因B细胞淋巴瘤/白血病-2（bcl-2）家族的成员可能是重要的决定因素。因此，本研究的目的是测试bcl-2是否调节出生时原始卵泡池的大小。为了验证这一假设，我们构建了三系转基因小鼠（c-kit/bcl-2小鼠），它们过度表达人类bcl-2，以减少产前卵母细胞损失。利用一个4.8千碱基的c-kit启动子，使这种过表达靶向卵巢并处于合适的胚胎时期。该启动子在卵巢中使bcl-2的表达增加了两到三倍，而在大多数非性腺组织中极少或没有过表达。在出生后第8 - 60天，从纯合c-kit/bcl-2小鼠和同窝非转基因小鼠（对照）中收集卵巢，并进行处理以对卵泡数量进行组织学评估。所有品系的c-kit/bcl-2小鼠出生时的原始卵泡数量都显著多于对照小鼠（P≤0.05）。然而，到出生后第30 - 60天，c-kit/bcl-2小鼠和对照小鼠之间的卵泡数量没有显著差异。这些结果表明，bcl-2过表达增加了出生时原始卵泡的数量，但出生后原始卵泡的过剩情况并未维持。这些数据表明，卵巢可能存在一种普查机制，通过该机制可以检测到出生时多余的原始卵泡，并在成年前将其从卵巢中清除。
