Cracd Marks the First Wave of Meiosis during Spermatogenesis and Is Mis-Expressed in Azoospermia Mice.
Cracd Marks the First Wave of Meiosis during Spermatogenesis and Is Mis-Expressed in Azoospermia Mice.
复制标题
DOI：
10.3390/jdb8030021
复制
发表时间：
2020-09-18
影响因子：
2.7
通讯作者：
Conway SJ
中科院分区：
文献类型：
--
作者：
Snider PL;Simmons O;Conway SJ
睾丸发育在子宫内开始，并在出生后继续成熟，需要一系列的基因激活和分化成不同的细胞类型，每种细胞类型都有其自己的特定功能。正如我们之前报道的，肌动蛋白抑制调节因子 (Cracd) 基因在成年小鼠睾丸中表达，本文中我们检查了 β-连环蛋白相关 Cracd 在出生后睾丸发育过程中最初表达的时间和地点。值得注意的是，Cracd mRNA 存在于未成熟的出生后和成年睾丸的圆形精子细胞中，在第一次减数分裂和精子发生期间表达水平最高。在幼年睾丸中，Cracd 最初在最内部区域表达，但随着成熟的发生，Cracd mRNA 切换到更外围的位置。此后，Cracd 在单倍体雄性生殖细胞谱系中下调至维持水平。由于 Cracd 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症生物标志物的有效性。有意义的是，Cracd 表达在无精症样（Dazl）无效睾丸中不存在，表现出生殖细胞的显着损失。此外，Cracd 在多嘧啶束结合蛋白 2 (Ptbp2) 条件性生殖细胞限制性敲除睾丸中受到异常调节和异位错误表达，在精子细胞分化过程中表现出受阻，并且晚期精母细胞数量减少，与 β-连环蛋白表达减少一致。综合起来，这些数据表明 Cracd 是无精症表型的有用的第一波精子发生生物标志物，甚至在明显的表型明显之前。
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 Capping protein inhibiting regulator of actin (Cracd) gene was expressed in the adult mouse testis, herein we examine when and where the β-catenin associated Cracd is initially expressed during postnatal testis development. Significantly, Cracd 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, Cracd is initially expressed within the innermost region but as maturation occurs, Cracd mRNA switches to a more peripheral location. Thereafter, Cracd is downregulated to maintenance levels in the haploid male germ cell lineage. As Cracd mRNA was expressed within developing round spermatids, we tested its effectiveness as a biomarker of non-obstructive azoospermia using transgenic knockout mice models. Meaningfully, Cracd expression was absent in Deleted in azoospermia like (Dazl) null testis, which exhibit a dramatic germ cell loss. Moreover, Cracd was abnormally regulated and ectopically mis-expressed in Polypyrimidine tract binding protein-2 (Ptbp2) 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 Cracd is a useful first wave of spermatogenesis biomarker of azoospermia phenotypes, even prior to an overt phenotype being evident.
登录
查看更多内容
影响因子：
8.8
作者：
Hannigan MM;Zagore LL;Licatalosi DD
通讯作者：
Licatalosi DD
影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
DOI：
10.1073/pnas.1635054100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Schultz, N;Hamra, FK;Garbers, DL
通讯作者：
Garbers, DL
影响因子：
3.7
作者：
Laiho A;Kotaja N;Gyenesei A;Sironen A
通讯作者：
Sironen A
影响因子：
3.1
作者：
Gong, Zu-Kang;Wang, Shuang-Jie;Lin, Wen-Zhen
通讯作者：
Lin, Wen-Zhen