Increased Female Fertility in Aquaporin 8-Deficient Mice
Increased Female Fertility in Aquaporin 8-Deficient Mice
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DOI：
10.1002/iub.398
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发表时间：
2010-11-01
期刊：
影响因子：
4.6
通讯作者：
Ma, Tonghui
中科院分区：
文献类型：
--
作者：
Su, Weiheng;Qiao, Ying;Ma, Tonghui
水通道蛋白-8 （Aquaporin-8, AQP8）是在男性和女性生殖系统中广泛表达的一个水通道。但它的生理功能在很大程度上是未知的。在本研究中，我们首先在交叉交配实验中发现AQP8（-/-）母鼠的后代数量明显高于野生型母鼠。两种基因型的排卵比较表明，AQP8（-/-）卵巢释放更多的卵母细胞（正常排卵9.5 +/- 1.9 vs. 7.1 +/- 2.1，超排卵37.8 +/- 6.7 vs. 27.9 +/- 5.7）。组织学分析显示成熟AQP8（-/-）卵巢黄体数量增加，提示卵泡成熟和排卵增加。采用RTPCR、western blot和免疫组化方法检测AQP8在小鼠卵巢颗粒细胞中的表达。AQP8（-/-）小鼠颗粒细胞的膜透水性比野生型小鼠降低45%。由于卵巢卵泡闭锁主要是由颗粒细胞凋亡引起的，我们分析了野生型和AQP8（-/-）小鼠分离颗粒细胞的凋亡情况。结果表明，AQP8（-/-）颗粒细胞的凋亡率明显降低（AQP8（+/+）颗粒细胞为21.3 +/- 3.6%，而AQP8（+/+）颗粒细胞为32.6 +/- 4.3%）。综上所述，我们得出结论，AQP8缺乏通过减少颗粒细胞的凋亡来增加成熟卵泡的数量，从而提高雌性小鼠的生育能力。这一发现可能为通过抑制AQP8减少颗粒细胞凋亡从而提高女性生育能力提供新的见解。(C) [j] .中国生物医学工程学报，2010,32 (11):852-857
Aquaporin-8 (AQP8) is a water channel expressed extensively in male and female reproductive systems. But its physiological functions are largely unknown. In the present study, we first found significantly increased number of offspring delivered by AQP8(-/-) mothers compared with wild-type mothers in cross-mating experiments. Comparison of ovulation in the two genotypes demonstrated that AQP8(-/-) ovaries released more oocytes (9.5 +/- 1.9 vs. 7.1 +/- 2.1 in normal ovulation and 37.8 +/- 6.7 vs. 27.9 +/- 5.7 in superovulation). Histological analysis showed increased number of corpus luteums in mature AQP8(-/-) ovaries, suggesting increased maturation and ovulation of follicles. By RTPCR, western blot and immunohistochemistry analyses, we determined the expression of AQP8 in mouse ovarian granulosa cells. Granulosa cells isolated from AQP8(-/-) mice showed 45% of decreased membrane water permeability than wild-type mice. As the atresia of ovarian follicles is primarily due to apoptosis of granulosa cells, we analyzed the apoptosis of isolated granulosa cells from wild-type and AQP8(-/-) mice. The results indicated significantly lower apoptosis rate in AQP8(-/-) granulosa cells (21.3 +/- 3.6% vs. 32.6 +/- 4.3% in AQP8(+/+) granulosa cells). Taken together, we conclude that AQP8 deficiency increases the number of mature follicles by reducing the apoptosis of granulosa cells, thus increasing the fertility of female mice. This discovery may offer new insight of improving female fertility by reducing granulosa cell apoptosis through AQP8 inhibition. (C) 2010 IUBMB IUBMB Life, 62(11): 852-857, 2010