Flaws J A, Abbud R, Mann R J, Nilson J H, Hirshfield A N
Department of Epidemiology/Preventive Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Biol Reprod. 1997 Nov;57(5):1233-7. doi: 10.1095/biolreprod57.5.1233.
A few years before reproductive senescence, primordial follicles are depleted from the ovary at a dramatically accelerated rate. It has been proposed that this depletion is due to transient increases in gonadotropin levels. To test this hypothesis, we used mice that produce chronically elevated levels of serum LH via expression of an LHbeta subunit transgene. Ovaries were collected from transgenic and control mice, and complete serial sections were prepared for histological examination. Each section was scanned for morphological abnormalities, and every fifth section was sampled to estimate the total number of primordial, primary, and large preantral follicles per ovary. Until 3 wk postpartum, ovaries from transgenic and control mice were morphologically similar. By 5 wk, control ovaries contained many healthy primordial, primary, and large preantral follicles as well as atretic follicles. Transgenic ovaries contained blood-filled cysts, misshapen granulosa cells, luteinized cells, and approximately 45% fewer primordial follicles than controls. By 3 mo, transgenic ovaries had about 68% fewer primordial follicles and 53% fewer primary follicles than controls. These results suggest that, in addition to having profound effects on growing follicles, chronically elevated LH levels deplete the primordial follicle pool and thus may hasten the onset of reproductive senescence.
在生殖衰老前的几年里，原始卵泡从卵巢中以显著加快的速度被耗尽。有人提出这种耗尽是由于促性腺激素水平的短暂升高所致。为了验证这一假设，我们使用了通过表达促黄体生成素β亚基转基因而使血清促黄体生成素水平长期升高的小鼠。从转基因小鼠和对照小鼠中收集卵巢，并制备完整的连续切片用于组织学检查。对每一片切片进行形态学异常扫描，并每隔五片取样以估计每个卵巢中原始卵泡、初级卵泡和大的窦前卵泡的总数。直到产后3周，转基因小鼠和对照小鼠的卵巢在形态上相似。到5周时，对照卵巢含有许多健康的原始卵泡、初级卵泡和大的窦前卵泡以及闭锁卵泡。转基因卵巢含有充满血液的囊肿、畸形的颗粒细胞、黄体化细胞，并且原始卵泡比对照少约45%。到3个月时，转基因卵巢的原始卵泡比对照少约68%，初级卵泡少53%。这些结果表明，除了对生长中的卵泡有深远影响外，促黄体生成素水平长期升高会耗尽原始卵泡库，从而可能加速生殖衰老的开始。
