Cdc14aは、精子形成、精子成熟、および男性の受胎可能性において役割を果たしている

Cdc14a has a role in spermatogenesis, sperm maturation and male fertility.

• Zongzhuang Wen
• Haixia Zhu
• Aizhen Zhang
• Jing Lin
• Guangkai Zhang
• Dongyue Liu
• Yu Xiao
• Chao Ye
• Daqing Sun
• Bin Wu
• Jian Zhang
• Jiangang Gao

抄録

Cdc14aは進化的に保存された二重特異的タンパク質ホスファターゼであり、異なる生物において異なる役割を果たしている。ヒトにおけるCdc14amutationは男性不妊の原因となることが報告されているが、男性生殖系の制御におけるCdc14aの具体的な役割は不明である。本研究では、男性生殖系におけるCdc14aの機能を調べるために、ノックアウトマウスを作製した。Cdc14aマウスでは、精子の数が減少し、精子の運動性が損なわれ、異常な形態の精子の割合が高くなっていた。Cdc14a雄マウスと野生型（WT）雌マウスを交配させたところ、雌の卵管内に受精卵が認められたが、その大部分は発生中に死滅した。また、Cdc14a精巣の精巣精管には一部空洞が認められた。このことから、Cdc14aをノックアウトすると減数分裂が抑制されることが示唆された。その後、Cdc25a、Wee1、PR-Set7などCdc14aの基質タンパク質の発現量を解析し、WT精巣と比較したところ、Cdc14a精巣ではこれらのタンパク質の発現量が有意に増加していた。その結果、Cdc14amaleマウスは高度な亜生殖能力を有しており、Cdc14aは正常な精子形成と精子機能に必須であることが明らかになった。

Cdc14a is an evolutionarily conserved dual-specific protein phosphatase, and it plays different roles in different organisms. Cdc14amutations in human have been reported to cause male infertility, while the specific role of Cdc14a in regulation of the male reproductive system remains elusive. In the present study, we established a knockout mouse model to study the function of Cdc14a in male reproductive system.Cdc14a male mice were subfertile and they could only produce very few offspring. The number of sperm was decreased, the sperm motility was impaired, and the proportion of sperm with abnormal morphology was elevated in Cdc14a mice. When we mated Cdc14a male mice with wild-type (WT) female mice, fertilized eggs could be found in female fallopian tubes, however, the majority of these embryos died during development. Some empty spaces were observed in seminiferous tubule of Cdc14a testes. Compared with WT male mice, the proportions of pachytene spermatocytes were increased and germ cells stained with γH2ax were decreased in Cdc14a male mice, indicating that knockout of Cdc14a inhibited meiotic initiation. Subsequently, we analyzed the expression levels of some substrate proteins of Cdc14a, including Cdc25a, Wee1, and PR-Set7, and compared those with WT testes, in which the expression levels of these proteins were significantly increased in Cdc14a testes. Our results revealed that Cdc14amale mice are highly subfertile, and Cdc14a is essential for normal spermatogenesis and sperm function.

Copyright © 2020. Published by Elsevier Inc.