Phospholipase Cγ2 Is Required for Luminal Expansion of the Epididymal Duct during Postnatal Development in Mice.
Phospholipase Cγ2 Is Required for Luminal Expansion of the Epididymal Duct during Postnatal Development in Mice.
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在小鼠产后发育过程中，需要磷脂酶Cγ2才能进行磷脂酶Cγ2。
DOI：
10.1371/journal.pone.0150521
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yoshida N
中科院分区：
文献类型：
--
作者：
Ichise H;Ichise T;Yoshida N
磷脂酶Cγ2（PLCγ2）缺陷小鼠表现出血管和淋巴管的错误连接以及雄性不育。然而，负责血管分配的细胞类型和男性不育的机制仍然未知。因此，我们产生了以Cre/loxP重组依赖性方式有条件地表达内源性Plcg 2的小鼠系，并且发现Tie 2-Cre-或Pf 4-Cre-驱动的Plcg 2的再活化从血管表型中拯救PLCγ2缺陷小鼠。相比之下，从血管表型中拯救出来的雄性小鼠表现出附睾精子肉芽肿。免疫组化显示，PLCγ2在附睾透明细胞中表达。出生后2周，PLCγ2缺乏并不影响附睾上皮细胞（包括透明细胞）的分化和小管形成。然而，管腔扩张的附睾管在青春期前期间受损，无论上皮细胞极性和管结构。这些结果表明，PLCγ2-缺陷的透明细胞导致管腔扩张受损，附睾管狭窄，管腔流动减弱，随后出现精子肉芽肿。尽管与PLCγ2缺陷相关的水肿和出血表型也会导致老年男性自发性附睾精子肉芽肿，但PLC γ 2缺陷男性可通过附睾上皮特异性Plcg 2再激活而免于不育，这一观察结果也支持了明确的细胞介导的管腔扩张。总的来说，我们的研究结果表明，PLCγ2在透明细胞在小鼠青春期前附睾腔扩张中起着重要作用，并揭示了PLCγ2，透明细胞和附睾发育之间的意外联系。
Phospholipase Cγ2 (PLCγ2)-deficient mice exhibit misconnections of blood and lymphatic vessels, and male infertility. However, the cell type responsible for vascular partitioning and the mechanism for male infertility remain unknown. Accordingly, we generated a mouse line that conditionally expresses endogenous Plcg2 in a Cre/loxP recombination-dependent manner, and found that Tie2-Cre- or Pf4-Cre-driven reactivation of Plcg2 rescues PLCγ2-deficient mice from the vascular phenotype. By contrast, male mice rescued from the vascular phenotype exhibited epididymal sperm granulomas. As judged from immunostaining, PLCγ2 was expressed in clear cells in the epididymis. PLCγ2 deficiency did not compromise differentiation of epididymal epithelial cells, including clear cells, and tube formation at postnatal week 2. However, luminal expansion of the epididymal duct was impaired during the prepubertal period, regardless of epithelial cell polarity and tube architecture. These results suggest that PLCγ2-deficient clear cells cause impaired luminal expansion, stenosis of the epididymal duct, attenuation of luminal flow, and subsequent sperm granulomas. Clear cell-mediated luminal expansion is also supported by the observation that PLCγ2-deficient males were rescued from infertility by epididymal epithelium-specific reactivation of Plcg2, although the edematous and hemorrhagic phenotype associated with PLCγ2 deficiency also caused spontaneous epididymal sperm granulomas in aging males. Collectively, our findings demonstrate that PLCγ2 in clear cells plays an essential role in luminal expansion of the epididymis during the prepubertal period in mice, and reveal an unexpected link between PLCγ2, clear cells, and epididymal development.