| First Author | Dai J | Year | 2022 |
| Journal | EMBO Mol Med | Volume | 14 |
| Issue | 12 | Pages | e16501 |
| PubMed ID | 36321563 | Mgi Jnum | J:332231 |
| Mgi Id | MGI:7407402 | Doi | 10.15252/emmm.202216501 |
| Citation | Dai J, et al. (2022) IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect. EMBO Mol Med 14(12):e16501 |
| abstractText | Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole-exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif-containing N (IQCN) were identified in two affected individuals with abnormal acrosome structures. Then, Iqcn-knockout mice were generated by CRISPR-Cas9 technology and showed that the knockout male mice resembled the human phenotypes. Additionally, we found that IQCN regulates microtubule nucleation during manchette assembly via calmodulin and related calmodulin-binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCzeta. Fortunately, ICSI with assisted oocyte activation can overcome IQCN-associate TFF and male infertility. Thus, our study firstly identified the function of IQCN, highlights the relationship between the manchette assembly and fertilization, and provides a genetic marker and a therapeutic option for male-source TFF. |
