Switching Mechanism for Meiosis Initiation or Apoptosis in Spermatogonia

精原细胞减数分裂启动或凋亡的转换机制

基本信息

批准号：
12680718
负责人：
ABE Shin-ichi
金额：
$ 2.37万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680718/
关键词：
Meiosis initiation Spermatogonia Apoptosis BMP-2 4 SCF c-kit newt FSH プロラクチン BMP-2 -4 BMP受容体

项目摘要

The regulatory mechanism controlling the initiation of meiosis during spermatogenesis is poorly understood. We previously reported that FSH is indispensable for the completion of the last spermatogonial mitosis, a prerequisite for the conversion of germ cells from mitosis to meiosis and we proposed that a checkpoint exists for the initiation of meiosis in the 7th generation whereby spermatogonia enter meiosis when the concentration ratio of FSH/PRL is high but fail to do so when the ratio is low. Candidates for meiosis Initiating factors are considered to be insulin-like growth factor (IGF)-I, stem cell factor (SCF), activin, and bone morphogenetic protein (BMP). Hence, cDNAs for SCF and BMP-2 were isolated and the mRNA expressions were studied.1) Human recombinant BMP-2 caused apoptosis in the 7th generation in organ culture of testis fragments as prolactin did. This apoptosis was rescued by FSH and IGF, but not SCF.2) Newt BMP-2 mRNA was expressed in somatic cell fraction in spermatogonial stage. Both BMP receptor I and II mRNA were expressed through spermatogonial to round spermatid stages.3) Human recombinant SCF (rhSCF) was found to stimulate the spermatogonial proliferation in organ culture of testicular fragments, and they progressed to the 7th generation. However, the spermatogonia did not differentiate into primary spermatocytes, but instead died of apoptosis.4) Newt SCF mRNA was expressed throughout all stages of spermatogenesis, while c-kit mRNA was highly expressed in spermatogonial and primary spermatocyte stages.

对精子发生过程中减数分裂起始的调节机制知之甚少。我们先前报道说，FSH对于完成最后一个精子有丝分裂是必不可少的，这是生殖细胞从有丝分裂变为减数分裂的先决条件，我们提议在第七代中存在减数症的检查站，即精子进入的浓度在fsh/prl iS pr low时，均通过了精子的浓度，但该检查点很高。减数分裂引发因子的候选物被认为是胰岛素样生长因子（IGF）-I，干细胞因子（SCF），激活素和骨形态发生蛋白（BMP）。因此，分离了SCF和BMP-2的CDNA，并研究了mRNA表达。1）人类重组BMP-2在睾丸片段的器官培养中引起第七代的凋亡，就像催乳素一样。 FSH和IGF挽救了这种凋亡，但不是SCF.2）NEWT BMP-2 mRNA在精子阶段的体细胞分数中表达。 BMP受体I和II mRNA均通过精子量表表达至圆形精子阶段。3）发现人重组SCF（RHSCF）刺激睾丸片段器官培养的精子增殖，并发展为第七代。然而，精子并未分化为原代精子细胞，而是死于凋亡。4）NEWT SCF mRNA在精子发生的所有阶段都表达，而C-KIT mRNA在精子和原代精子细胞阶段高度表达。