• PMID: 28964737
• Gene Name: HSPB11
• Condition: Controls sperm formation, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Controls sperm formation, Male infertility

Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice

Zhang Y, Liu H, Li W, Zhang Z, Shang X, Zhang D, Li Y, Zhang S, Liu J, Hess RA, Pazour GJ, Zhang Z.

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27: Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survived to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymides contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the "9+2″ axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the conditional Ift25 knockout mice, appeared to be normal in the conditional Ift27 knockout mice. Our findings suggest that like IFT25, IFT27, even though not required for ciliogenesis in somatic cells, is essential for sperm flagella formation, sperm function, and male fertility in mice. IFT25 and IFT27 control sperm formation/function through many common mechanisms, but IFT25 has additional roles beyond IFT27. CI - Published by Elsevier Inc. FAU - Zhang, Yong AU - Zhang Y AD - Department of Dermatology, Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA. FAU - Liu, Hong AU - Liu H AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA; School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei 430060, China. FAU - Li, Wei AU - Li W AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA. FAU - Zhang, Zhengang AU - Zhang Z AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA; Department of Gastroenterology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Shang, Xuejun AU - Shang X AD - Department of Andrology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China. FAU - Zhang, David AU - Zhang D AD - Godwin High School, 2101 Pump Rd, Richmond, VA 23238, USA. FAU - Li, Yuhong AU - Li Y AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA; Department of Pathology, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430060, China. FAU - Zhang, Shiyang AU - Zhang S AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA; School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei 430060, China. FAU - Liu, Junpin AU - Liu J AD - Department of Obstetrics&Gynecology, Virginia Commonwealth University, Richmond, VA, 23298, USA; Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, Wuhan 430000, Hubei, China. FAU - Hess, Rex A AU - Hess RA AD - Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln, Urbana, IL 61802-6199, USA. FAU - Pazour, Gregory J AU - Pazour GJ AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.