Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1.
Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1.
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DOI：
10.1095/biolreprod.109.077925
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发表时间：
2010-03
影响因子：
3.6
通讯作者：
Hixon ML
中科院分区：
文献类型：
--
作者：
Brown C;LaRocca J;Pietruska J;Ota M;Anderson L;Smith SD;Weston P;Rasoulpour T;Hixon ML
哺乳动物雌性在出生时被赋予有限数量的原始卵泡。在原始卵泡池形成后，立即从卵巢中剔除卵泡群，或者招募卵泡群生长，直到原始卵泡群耗尽。大多数卵泡，包括卵母细胞，通过细胞凋亡发生闭锁。由于已知PKBalpha/Akt 1调节细胞凋亡，我们询问Akt 1是否在卵巢卵泡发生的调节中起作用。Akt 1 −/−雌性显示生育能力降低和异常的发情周期。在出生后第25天（PND），Akt 1 −/−卵巢中生长的有腔卵泡数量减少，初级和次级卵母细胞明显增大，退化卵母细胞数量增加。到PND 90时，Akt 1 −/−卵巢中的原始卵泡数量相对于Akt 1 +/+显著减少。体内颗粒细胞增殖减少，Kitl和Bcl 2l 1的表达水平也是如此，Kitl和Bcl 2l 1是与颗粒细胞增殖/存活相关的两个因素。Akt 2或Akt 3在mRNA/蛋白水平上没有观察到补偿作用。相对于Akt 1 +/+雌性，在Akt 1 −/−雌性中观察到血清LH显著较高，FSH较低，且FSH结合素A较高，结合素B较低。暴露于外源性促性腺激素导致Akt 1 −/−卵巢中次级卵泡数量增加，但成熟卵泡很少。总的来说，我们的研究结果表明，PKB α/Akt 1在卵巢的生长和成熟的调节中起着重要的作用，PKB α/Akt 1的丢失导致卵巢早衰。
Mammalian females are endowed with a finite number of primordial follicles at birth. Immediately following formation of the primordial follicle pool, cohorts of follicles are either culled from the ovary or are recruited to grow until the primordial follicle population is depleted. The majority of ovarian follicles, including the oocytes, undergo atresia through apoptotic cell death. As PKBalpha/Akt1 is known to regulate apoptosis, we asked whether Akt1 functioned in the regulation of folliculogenesis in the ovary. Akt1−/− females display reduced fertility and abnormal estrous cyclicity. At Postnatal Day (PND) 25, Akt1−/− ovaries possessed a reduced number of growing antral follicles, significantly larger primary and secondary oocytes, and an increase in the number of degenerate oocytes. By PND90, there was a significant decrease in the number of primordial follicles in Akt1−/− ovaries relative to Akt1+/+. In vivo granulosa cell proliferation was reduced, as were expression levels of Kitl and Bcl2l1, two factors associated with granulosa cell proliferation/survival. No compensation was observed by Akt2 or Akt3 at the mRNA/protein level. Significantly higher serum LH and trends for lower FSH and higher inhibin A and lower inhibin B relative to Akt1+/+ females were observed in Akt1−/− females. Exposure to exogenous gonadotropins resulted in an increase in the number of secondary follicles in Akt1−/− ovaries, but few mature follicles. Collectively, our results suggest that PKBalpha/Akt1 plays an instrumental role in the regulation of the growth and maturation of the ovary, and that the loss of PKBalpha/Akt1 results in premature ovarian failure.
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影响因子：
4.8
作者：
Rasoulpour, Teresa;DiPalma, Kathryn;Hixon, Mary
通讯作者：
Hixon, Mary
影响因子：
4.8
作者：
Andersen, CB;Roth, RA;Conti, M
通讯作者：
Conti, M
影响因子：
4.8
作者：
McMullen, ML;Cho, BN;Mayo, KE
通讯作者：
Mayo, KE
影响因子：
2.7
作者：
PACKER, AI;HSU, YC;BACHVAROVA, RF
通讯作者：
BACHVAROVA, RF
影响因子：
2.8
作者：
Picton, HM
通讯作者：
Picton, HM