Abstract
Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation.
Highlights
Antisense oligonucleotides induced a double-axis phenotype during neurogenesis[14]; further studies are required to fully determine the biological function of Mkrn[2] in mammals
Mkrn[2] is a new member of the highly evolutionarily conserved makorin family, and it maybe originally created by gene duplication of MKRN1 approximately 450 million years ago[13]
Male Mkrn[2] knockout mice were found to be sterile, and no pups were born during the 4-month period of mating with female mice
Summary
Antisense oligonucleotides induced a double-axis phenotype during neurogenesis[14]; further studies are required to fully determine the biological function of Mkrn[2] in mammals. To investigate the function of the MKRN2 gene, we generated Mkrn2-knockout mice. Based on the results of our previous study, we expected that deletion of Mkrn[2] in mice may result indeficiency in the development of neurogenesis[14]. Mkrn2-knockout mice were viable with detectable abnormal neurogenesis, but the male mice were sterile. As mice and human share similar process of spermiogenesis and spermiation[15], these infertile Mkrn2-knockout mice could serve as an in vivo model to investigate the biological function of MKRN2 in human spermiogenesis and spermiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
