Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice

Outer dense fibre 2 (Odf2 or ODF2) is a cytoskeletal protein required for flagella ( tail)-beating and stability to transport sperm cellsfrom testes to the eggs. There are infertile males, including human patients, who have a high percentage of decapitatedand decaudated spermatozoa (DDS), whose semen contains abnormal spermatozoa with tailless heads and headless tailsdue to head-neck separation. DDS is untreatable in reproductive medicine. We report for the first time a new type of Odf2-DDS in heterozygous mutant Odf2+/− mice. Odf2+/− males were infertile due to haploinsufficiencycaused by heterozygous deletion of the Odf2 gene, encoding the Odf2 proteins. Odf2 haploinsufficiencyinduced sperm neck-midpiece separation, a new type of head- tailseparation, leading to the generation of headneck sperm cellsor headnecks composed of heads with necks and neckless tailscomposed of only the main parts of tails. The headnecks were immotile but alive and capable of producing offspring by intracytoplasmic headneck sperm injection (ICSI). The neckless tailswere motile and could induce capacitation but had no significant forward motility. Further studies are necessary to show that ICSI in humans, using headneck sperm cells, is viable and could be an alternative for infertile patients suffering from Odf2-DDS.