Caires Kyle C, de Avila Jeanene, McLean Derek J
Department of Animal Sciences, Berry College , School of Math and Natural Sciences, Mount Berry, Georgia .
Biores Open Access. 2012 Oct;1(5):222-30. doi: 10.1089/biores.2012.0259.
A balance between self-renewal and differentiation of spermatogonial stem cells (SSCs) is required to maintain sperm production throughout male life. The seminiferous epithelium is organized into stages of spermatogenesis based on the complement of germ cell types within a tubular section of the testis. The stages exist in close physical proximity and foster diverse phases of germ cell development despite exposure to a similar endocrine milieu that supports coordinated spermatogenesis. The objective of the current study was to identify the population dynamics of SSCs in vivo. We hypothesized that SSC populations and their niches are specifically distributed across the mature seminiferous epithelium in the mouse testis. To test this hypothesis, we conducted stem cell transplantation of germ cells obtained from stage-specific clusters of seminiferous tubules representing areas of high responsiveness to follicle-stimulating hormone (IX-I), androgen (II-IV), and retinoid (V-VIII) signaling. Similarly, we analyzed the expression of genes linked with SSC activity in these groups of stages. No stage-specific differences in the colonization efficiency or the colony number were detected after SSC transplantation, indicating that SSCs are equally distributed across all stages of the seminiferous tubule. In contrast, SSCs obtained from donor stages IX-IV established larger donor-derived colonies due to increased colony expansion. SSCs originating from different stages have varying degrees of stem cell activity in vivo, a notion consistent with Gdnf, Ret, and Bcl6b expression data. These results support the conclusion of a stage-specific, microenvironment-regulating SSC self-renewal and suggest the presence of a transit-amplifying population of undifferentiated spermatogonia in vivo.
为了在男性一生中维持精子生成,精原干细胞(SSCs)的自我更新与分化之间需要保持平衡。基于睾丸管状切片内生殖细胞类型的互补性,生精上皮被组织成精子发生的各个阶段。尽管暴露于支持协调精子发生的相似内分泌环境中,但这些阶段在物理上紧密相邻,并促进生殖细胞发育的不同阶段。本研究的目的是确定体内SSCs的群体动态。我们假设SSC群体及其微环境在小鼠睾丸的成熟生精上皮中特异性分布。为了验证这一假设,我们对从代表对促卵泡激素(IX-I)、雄激素(II-IV)和视黄酸(V-VIII)信号高度反应区域的生精小管阶段特异性簇中获得的生殖细胞进行了干细胞移植。同样,我们分析了这些阶段组中与SSC活性相关基因的表达。SSC移植后,未检测到定植效率或集落数的阶段特异性差异,表明SSCs在生精小管的所有阶段均匀分布。相反,由于集落扩张增加,从供体阶段IX-IV获得的SSCs建立了更大的供体来源集落。源自不同阶段的SSCs在体内具有不同程度的干细胞活性,这一概念与Gdnf、Ret和Bcl6b表达数据一致。这些结果支持了阶段特异性微环境调节SSC自我更新的结论,并表明体内存在未分化精原细胞的过渡放大群体。