Switching Mechanism for Meiosis Initiation or Apoptosis in Spermatogonia

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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.