Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, Cantoblanco, 28049, Madrid, Spain.
Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Sci Rep. 2022 Jun 29;12(1):10956. doi: 10.1038/s41598-022-15167-w.
Spermatogenesis is a complex, multistep process during which spermatogonia give rise to spermatozoa. Transcription Factor Like 5 (TCFL5) is a transcription factor that has been described expressed during spermatogenesis. In order to decipher the role of TCFL5 during in vivo spermatogenesis, we generated two mouse models. Ubiquitous removal of TCFL5 generated by breeding TCFL5 with SOX2-Cre mice resulted in sterile males being unable to produce spermatozoa due to a dramatic alteration of the testis architecture presenting meiosis arrest and lack of spermatids. SYCP3, SYCP1 and H1T expression analysis showed that TCFL5 deficiency causes alterations during pachytene/diplotene transition resulting in a meiotic arrest in a diplotene-like stage. Even more, TCFL5 deficient pachytene showed alterations in the number of MLH1 foci and the condensation of the sexual body. In addition, tamoxifen-inducible TCFL5 knockout mice showed, besides meiosis phenotype, alterations in the spermatids elongation process resulting in aberrant spermatids. Furthermore, TCFL5 deficiency increased spermatogonia maintenance genes (Dalz, Sox2, and Dmrt1) but also increased meiosis genes (Syce1, Stag3, and Morc2a) suggesting that the synaptonemal complex forms well, but cannot separate and meiosis does not proceed. TCFL5 is able to bind to the promoter of Syce1, Stag3, Dmrt1, and Syce1 suggesting a direct control of their expression. In conclusion, TCFL5 plays an essential role in spermatogenesis progression being indispensable for meiosis resolution and spermatids maturation.
精子发生是一个复杂的、多步骤的过程，在此过程中精原细胞产生精子。转录因子样 5（TCFL5）是一种转录因子，已被描述在精子发生过程中表达。为了解 TCFL5 在体内精子发生中的作用，我们生成了两种小鼠模型。通过将 TCFL5 与 SOX2-Cre 小鼠杂交，使其在全身表达缺失，导致雄性不育，无法产生精子，这是由于睾丸结构的剧烈改变，出现减数分裂阻滞和精母细胞缺乏。SYCP3、SYCP1 和 H1T 表达分析表明，TCFL5 缺失导致在粗线期/双线期转换过程中发生改变，导致减数分裂停滞在双线期样阶段。更重要的是，TCFL5 缺失的粗线期表现出联会复合体的改变，导致减数分裂停滞。此外，他莫昔芬诱导的 TCFL5 敲除小鼠除了表现出减数分裂表型外，还表现出精子伸长过程的改变，导致精子异常。此外，TCFL5 缺失增加了精原细胞维持基因（Dalz、Sox2 和 Dmrt1），但也增加了减数分裂基因（Syce1、Stag3 和 Morc2a），这表明联会复合体形成良好，但不能分离，减数分裂不能进行。TCFL5 能够结合 Syce1、Stag3、Dmrt1 和 Syce1 的启动子，提示其对这些基因的表达具有直接调控作用。总之，TCFL5 在精子发生进展中起着至关重要的作用，对于减数分裂的解决和精子成熟是不可或缺的。
