Snider Paige L, Simmons Olga, Conway Simon J
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46033, USA.
J Dev Biol. 2020 Sep 18;8(3):21. doi: 10.3390/jdb8030021.
Testicular development starts in utero and maturation continues postnatally, requiring a cascade of gene activation and differentiation into different cell types, with each cell type having its own specific function. As we had previously reported that the gene was expressed in the adult mouse testis, herein we examine when and where the β-catenin associated is initially expressed during postnatal testis development. Significantly, mRNA is present in both the immature postnatal and adult testis in round spermatid cells, with highest level of expression occurring during the first wave of meiosis and spermatogenesis. In the juvenile testes, is initially expressed within the innermost region but as maturation occurs, mRNA switches to a more peripheral location. Thereafter, is downregulated to maintenance levels in the haploid male germ cell lineage. As mRNA was expressed within developing round spermatids, we tested its effectiveness as a biomarker of non-obstructive azoospermia using transgenic knockout mice models. Meaningfully, expression was absent in null testis, which exhibit a dramatic germ cell loss. Moreover, was abnormally regulated and ectopically mis-expressed in conditional germ cell restricted knockout testis, which exhibit a block during spermatid differentiation and a reduction in the number of late stage spermatocytes coincident with reduced β-catenin expression. Combined, these data suggest that is a useful first wave of spermatogenesis biomarker of azoospermia phenotypes, even prior to an overt phenotype being evident.
睾丸发育始于子宫内，出生后仍在持续成熟，这需要一系列基因激活并分化为不同的细胞类型，每种细胞类型都有其特定功能。正如我们之前报道该基因在成年小鼠睾丸中表达，在此我们研究在出生后睾丸发育过程中，β-连环蛋白相关基因最初在何时何地表达。值得注意的是，该基因的信使核糖核酸（mRNA）在出生后未成熟和成年睾丸的圆形精子细胞中均有存在，在减数分裂和精子发生的第一波过程中表达水平最高。在幼年睾丸中，该基因最初在最内部区域表达，但随着成熟过程的进行，其mRNA转移到更外围的位置。此后，在单倍体雄性生殖细胞谱系中，该基因被下调至维持水平。由于该基因的mRNA在发育中的圆形精子细胞中表达，我们使用转基因敲除小鼠模型测试了其作为非梗阻性无精子症生物标志物的有效性。有意义的是，在该基因敲除的睾丸中不存在该基因的表达，这些睾丸表现出明显的生殖细胞损失。此外，在条件性生殖细胞限制性敲除的睾丸中，该基因受到异常调节且异位错误表达，这些睾丸在精子细胞分化过程中出现阻滞，晚期精母细胞数量减少，同时β-连环蛋白表达降低。综合这些数据表明，即使在明显的表型出现之前，该基因也是无精子症表型有用的精子发生第一波生物标志物。
