Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling.

Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling.
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小鼠通过溶血磷脂酸信号传导的年龄依赖性精子产生损失。

DOI:
10.1095/biolreprod.108.068783
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发表时间:
2008-08
影响因子:
3.6
通讯作者:
Chun, Jerold
Chun, Jerold
中科院分区:
生物学2区
文献类型:
--
作者:
Ye, Xiaoqin;Skinner, Michael K.;Kennedy, Grace;Chun, Jerold

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大约一半的不育病例可归因于男性生殖功能障碍,其中精子数量低是一个主要因素。目前的研究确定受体介导的溶血磷脂酸(LPA)信号作为一个新的分子组成部分影响男性生育力。LPA是一种小信号磷脂,其作用通过至少五种G蛋白偶联受体(LPA 1 -5)介导。Lpa 1/2/3在小鼠睾丸中高度表达,而Lpa 4/5则不表达。lpa 1/2/3基因三重敲除的雄性小鼠表现出不依赖于睾丸激素的交配活动和精子产生的减少,老年动物中无精子症的患病率增加。在Lpa 1/2/3基因敲除的睾丸中观察到生殖细胞凋亡的显著增加。生殖细胞凋亡导致生殖细胞增殖减少。这些数据证明了LPA信号作为精子发生过程中的生殖细胞存活因子的一种新的体内功能。
Approximately half of all infertility cases can be attributed to male reproductive dysfunction for which low sperm count is a major contributing factor. The current study identified receptor-mediated lysophosphatidic acid (LPA) signaling as a new molecular component influencing male fertility. LPA is a small signaling phospholipid whose effects are mediated through at least five G protein-coupled receptors, named LPA1–5. Lpa1/2/3, but not Lpa4/5, are highly expressed in mouse testis. Lpa1/2/3-triple knockout male mice showed a testosterone-independent reduction of mating activity and sperm production, with an increased prevalence of azoospermia in aging animals. A significant increase of germ cell apoptosis was observed in the Lpa 1/2/3-triple knockout testes. Germ cell apoptosis led to a reduction in germ cell proliferation. These data demonstrate a novel in vivo function for LPA signaling as a germ cell survival factor during spermatogenesis.
DOI: 10.1083/jcb.135.4.1071
发表时间: 1996-11
期刊: The Journal of cell biology
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