Decreased Oocyte DAZL Expression in Mice Results in Increased Litter Size by Modulating Follicle-Stimulating Hormone-Induced Follicular Growth
Decreased Oocyte DAZL Expression in Mice Results in Increased Litter Size by Modulating Follicle-Stimulating Hormone-Induced Follicular Growth
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DOI：
10.1095/biolreprod.110.086264
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发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
McNeilly, Alan S.
中科院分区：
文献类型：
--
作者：
McNeilly, Judith R.;Watson, Elaine A.;McNeilly, Alan S.
虽然生殖细胞特异性RNA结合蛋白DAZL是卵母细胞在减数分裂停滞中存活所必需的，但DAZL杂合（het）小鼠的排卵率增加，这与升高的卵泡刺激素B和降低的血浆卵泡刺激素（FSH）有关。使用体外卵泡培养和体内内源性FSH调节，通过用Escherichin和外源性FSH处理小鼠，研究了het小鼠中卵母细胞DAZL表达降低和卵泡发育增强之间的关系。在体外，来自het小鼠的卵泡比野生型（wt）小鼠的卵泡对FSH更敏感，并且可以在对野生型卵泡有害的FSH浓度下生长。在体内，尽管在卵泡群体概况的基因型之间没有差异，在有腔卵泡的颗粒细胞面积的分析确定了一个显着更多的有腔卵泡的颗粒细胞面积增加het卵巢。在体内使用剂量递减的FSH或绵羊卵泡液作为FSH的来源，对FSH进行调节，证实了het窦卵泡对FSH的反应性增加。显着更多的卵泡表达芳香化酶蛋白证实了het小鼠颗粒细胞的早期成熟。总之，这表明DAZL表达抑制特定的未知基因，调节颗粒细胞对FSH的反应。如果这种抑制减少，如在DAZL het小鼠中，那么尽管循环FSH水平下降，卵泡仍可以生长到卵泡晚期，从而导致更多的卵泡排卵和窝仔数增加。
While the germ cell-specific RNA binding protein, DAZL, is essential for oocytes to survive meiotic arrest, DAZL heterozygous (het) mice have an increased ovulation rate that is associated with elevated inhibin B and decreased plasma follicle-stimulating hormone (FSH). The relationship between decreased oocyte DAZL expression and enhanced follicular development in het mice was investigated using in vitro follicle cultures and in vivo modulation of endogenous FSH, by treating mice with inhibin and exogenous FSH. In vitro, follicles from het mice are more sensitive to FSH than those of wild-type (wt) mice and can grow in FSH concentrations that are deleterious to wildtype follicles. In vivo, despite no differences between genotypes in follicle population profiles, analysis of granulosa cell areas in antral follicles identified a significantly greater number of antral follicles with increased granulosa cell area in het ovaries. Modulation of FSH in vivo, using decreasing doses of FSH or ovine follicular fluid as a source of inhibin, confirmed the increased responsiveness of het antral follicles to FSH. Significantly more follicles expressing aromatase protein confirmed the earlier maturation of granulosa cells in het mice. In conclusion, it is suggested that DAZL expression represses specific unknown genes that regulate the response of granulosa cells to FSH. If this repression is reduced, as in DAZL het mice, then follicles can grow to the late follicular stage despite declining levels of circulating FSH, thus leading to more follicles ovulating and increased litter size.