Switching Mechanism for Meiosis Initiation or Apoptosis in Spermatogonia

在精子发生过程中控制减数分裂起始的调节机制知之甚少。我们以前曾报道，FSH是必不可少的完成最后的精原细胞有丝分裂，从有丝分裂到减数分裂的生殖细胞的转换的先决条件，我们提出了一个检查点存在于第7代减数分裂的启动，从而精原细胞进入减数分裂时，FSH/PRL的浓度比高，但不能这样做时，该比例低。减数分裂起始因子的候选者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，我们分离了SCF和BMP-2的cDNA，并研究了其mRNA的表达。1）人重组BMP-2在第7代睾丸组织培养中与催乳素一样引起细胞凋亡。FSH和IGF能挽救细胞凋亡，而SCF不能。2）Newt BMP-2 mRNA在精原细胞期的体细胞部分表达。BMP受体I和II的mRNA在精原细胞至圆形精子细胞阶段均有表达。3）重组人SCF（rhSCF）可刺激睾丸组织培养中的精原细胞增殖，并可持续至第7代。4）Newt SCF mRNA在精子发生的各个阶段均有表达，而c-kit mRNA在精原细胞和初级精母细胞阶段均有高表达。

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.