Zhao Jun, Ma Wenmin, Zhong Yucheng, Deng Hao, Zhou Bingyu, Wu Yaqin, Yang Meiqiong, Li Huan
Assisted Reproductive Technology Center, Foshan Maternal and Child Health Care Hospital, Foshan, China.
Front Mol Biosci. 2021 Mar 11;8:652392. doi: 10.3389/fmolb.2021.652392. eCollection 2021.
Our previous study found that lncRNA gadd7 was up-regulated in the semen of varicocele patients, and could promote the apoptosis of mouse spermatocytes and inhibit their proliferation. Therefore, we further explored whether down-regulation of Gadd seven expression could protect the viability of spermatocytes. Here we designed specific sgRNAs targeting the ORF region of gadd7, and constructed a CRISPR-dCas9-KRAB system that effectively inhibits gadd7 at the transcriptional level. The CRISPRi system can effectively prevent the apoptosis of spermatocytes and enhance their proliferation, which is expected to provide a potentially effective molecular intervention method for the treatment of male infertility caused by varicocele.
我们先前的研究发现，lncRNA gadd7在精索静脉曲张患者的精液中上调，并且可以促进小鼠精母细胞的凋亡并抑制其增殖。因此，我们进一步探究下调Gadd seven的表达是否可以保护精母细胞的活力。在此，我们设计了靶向gadd7开放阅读框区域的特异性sgRNA，并构建了在转录水平有效抑制gadd7的CRISPR-dCas9-KRAB系统。该CRISPRi系统可以有效防止精母细胞凋亡并增强其增殖，有望为精索静脉曲张所致男性不育的治疗提供一种潜在有效的分子干预方法。
