Dataset Information

IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect

ABSTRACT: Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remain 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 structure. Then, Iqcn knockout mice were generated by CRISPR-Cas9 technology and showed that the knockout male mice resembled TFF phenotype with oocyte activation failure. Additionally, we found that IQCN regulates the microtubule nucleation during manchette assembly via calmodulin and related calmodulin-binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCζ. Fortunately, ICSI with assisted oocyte activation can overcome IQCN-associate male infertility. Thus, our study firstly identifies 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Testis

SUBMITTER: Jing Dai

LAB HEAD: Ge Lin

PROVIDER: PXD036197 | Pride | 2022-11-22

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 6

Publications

IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect.

Dai Jing J Li Qi Q Zhou Qinwei Q Zhang Shen S Chen Junru J Wang Yize Y Guo Jing J Gu Yifan Y Gong Fei F Tan Yueqiu Y Lu Guangxiu G Zheng Wei W Lin Ge G

EMBO molecular medicine 20221102 12

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 tec ...[more]

PMID: 36321563

Similar Datasets

Project description:Infertility is a widespread problem, affecting around 15% of couples worldwide, and is defined as the inability to achieve pregnancy within one year despite unprotected intercourse 1. Infertility can be caused by either male or female reproductive issues. Various medical conditions including malignancies, infections, urogenital conditions, or genetic causes can contribute to male infertility. However, 30-40% of men in their reproductive age are affected by idiopathic infertility, according to the guidelines of European Association of Urology (EAU) 1. Towards a better understanding of male infertility, it is mandatory to achieve a comprehensive understanding of involved genes, their RNA transcripts, and regulatory factors, including miRNAs, which influence the expression level of proteins. Therefore, such proteins need to be identified to investigate their role in spermatogenesis and male infertility. Although there are numerous studies on RNAs, including miRNAs related to male infertility 2-9, there are few studies aiming to cover the whole proteome of human sperm 10. The sperm transcriptome comprises a total of 60,505 transcripts including 11,688 differentially expressed transcripts in infertile and fertile men, as reported by Joshi et al. (2022)11. The entire sperm proteome encompasses 6871 proteins, as summarized by Castillo et al. (2018)10. Nevertheless, there is still a lack of high-throughput studies aiming to identify dysregulated proteins in sperm from subfertile men. Only few studies focused on comparisons of the sperm proteome in men with asthenozoospermia and there is virtually no proteomic studies of oligoasthenozoospermic men 12. Some identified proteins in sperm have functions in maintaining sperm motility and enabling fertilization and are involved in structural composition and/or energy metabolism 12-14 and others are not yet functionally characterized. In this study, we employed Mass spectrometry (MS) technology that is still rarely used in the field of human reproductive research to investigate the proteomic landscape of human sperm and their differential expression patterns in men with subfertility.

			Action	DRS
	RE158LQ_KO_1.raw	Raw
	RE158LQ_KO_2.raw	Raw
	RE158LQ_WT_1.raw	Raw
	RE158LQ_WT_2.raw	Raw
	checksum.txt	Txt