Meinhardt A, McFarlane J R, Seitz J, de Kretser D M
Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, 246 Clayton Rd, Melbourne, Victoria, Australia.
Mol Cell Endocrinol. 2000 Oct 25;168(1-2):111-7. doi: 10.1016/s0303-7207(00)00308-7.
Development of germ cells during spermatogenesis is characterized by a complex series of differentiation events finally leading to the production of spermatozoa. Beside the main hormonal regulators, paracrine interactions are thought to play a major role in this process. Mitochondria in germ cells pass through unique alterations ranging from the 'typical' cristae-rich mitochondria found in spermatogonia to the 'condensed' form in pachytene spermatocytes. This study provides further support that paracrine factors produced by Sertoli cells, most likely activin A, are involved in germ cell differentiation as monitored by the maintenance of the physiological 'condensed' mitochondrial phenotype in primary spermatocytes. Culture of primary spermatocytes in Sertoli cell conditioned medium (SCCM) for 18 h resulted in the maintenance of a high percentage of 'condensed-type' mitochondria in comparison to cells cultured in Dulbecco's minimum essential medium (DMEM). Activin A, a product of Sertoli cells, showed at subnanogram concentrations a similar ability to SCCM to maintain a high percentage of spermatocyte mitochondria in the 'condensed' state, while inhibin had no effect. The addition of an antiserum specific for activin A resulted in a neutralization of the effect caused by activin A or SCCM. This strongly suggested that the active substance in SCCM was activin A. Taken together these data indicate that activin A is the first Sertoli cell product that has been identified to influence differentiation of male meiotic germ cells.
精子发生过程中生殖细胞的发育以一系列复杂的分化事件为特征,最终导致精子的产生。除了主要的激素调节因子外,旁分泌相互作用被认为在这一过程中起主要作用。生殖细胞中的线粒体经历独特的变化,从精原细胞中发现的“典型”富含嵴的线粒体到粗线期精母细胞中的“浓缩”形式。本研究进一步支持,由支持细胞产生的旁分泌因子,很可能是激活素A,参与生殖细胞分化,这可通过初级精母细胞中生理“浓缩”线粒体表型的维持来监测。与在杜尔贝科改良伊格尔培养基(DMEM)中培养的细胞相比,将初级精母细胞在支持细胞条件培养基(SCCM)中培养18小时可使高比例的“浓缩型”线粒体得以维持。激活素A是支持细胞的产物,在亚纳克浓度下显示出与SCCM类似的能力,可使高比例的精母细胞线粒体维持在“浓缩”状态,而抑制素则无作用。添加针对激活素A的抗血清可中和激活素A或SCCM引起的效应。这强烈表明SCCM中的活性物质是激活素A。综上所述,这些数据表明激活素A是首个被鉴定出影响雄性减数分裂生殖细胞分化的支持细胞产物。