Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro.
Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro.
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DOI：
10.1093/humrep/16.4.757
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发表时间：
2001-04
影响因子：
6.1
通讯作者：
J. Blerkom;P. Davis
中科院分区：
文献类型：
--
作者：
J. Blerkom;P. Davis
研究了间隔1~6周的四轮卵巢刺激对正常小鼠卵母细胞中期II期纺锤体形成、染色体排列和细胞质结构的影响，以及对同一卵巢生发泡期获得的体外成熟卵母细胞进行中期II期卵母细胞体外成熟的影响。用末端脱氧核苷酸转移酶介导的dUDP缺口末端标记法检测染色体DNA链断裂，并对每一轮刺激前后的卵巢进行组织学观察。结果表明，随着每一轮卵巢刺激，包括间隔数周的刺激，纺锤体缺陷的频率逐渐显著增加。纺锤体缺陷的卵母细胞还具有分离的染色体和细胞质紫苏的特征。相比之下，来自同一卵巢的体外成熟卵母细胞是正常的。在排卵或体外成熟的卵母细胞中，没有发现重复几轮卵巢刺激导致DNA链断裂的证据。在发生卵泡生长的区域，肥大的颗粒结节的发展和持续表明，排卵途径中的卵母细胞比例逐渐增加，可能会经历卵泡内环境，这对能力有负面影响。结果讨论了卵巢和卵母细胞的生物老化，以及重复超刺激对人类卵母细胞能力的可能不利影响。
The effects of four rounds of ovarian stimulation spaced 1-6 weeks apart on the normality of metaphase II (MII) spindle formation, chromosomal alignment and cytoplasmic organization were examined in intact ovulated mouse oocytes and at MII for oocytes obtained at the germinal vesicle stage from the same ovaries and matured in vitro. The terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay was used to identify DNA strand breaks in chromosomes, and histological studies of ovaries between and at each round of ovarian stimulation were performed. The results demonstrate a progressive and significant increase in the frequency of spindle defects with each round of ovarian stimulation, including those spaced weeks apart. Oocytes with spindle defects were also characterized by the occurrence of detached chromosomes and cytoplasmic asters. In contrast, in-vitro matured oocytes derived from the same ovaries were normal. No evidence of DNA strand breaks with repeated rounds of ovarian stimulation was detected in ovulated or in-vitro matured oocytes. The development and persistence of nodules of hypertrophied granulosa in regions where follicular growth occurs suggest that a progressively increasing proportion of oocytes in the ovulatory pathway may experience an intrafollicular milieu that has negative consequences for competence. The results are discussed with respect to ovarian and oocyte biological ageing and possible adverse implications for human oocyte competence with repeated hyperstimulation.