Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage

Abstract

The small heat shock protein ODF1/HSPB10 is essential for male fertility in mice. Targeted deletion of Odf1 resulted in acephalic sperm in homozygous mice of mixed background (C57BL/6J//129/Sv), whereas heterozygous animals are fully fertile. To further elucidate the function of ODF1, we generated incipient congenic mice with targeted deletion of Odf1 by successive backcrossing on the 129/Sv background. We observed that fecundity of heterozygous Odf1 C/K male mice was severely reduced over backcross generations. However, neither aberrant sperm parameters nor sperm anomalies could be observed. Ultra-structural analyses of sperm from incipient congenic heterozygous Odf1 C/K males of backcross generation N7 revealed no obvious pathological findings. However, we observed an enlargement of the distance between nuclear membrane and capitulum, indicating a weakening of the sperm head-to-tail coupling. Severe male subfertility provoked by haplo-deficiency of ODF1 is therefore most probably caused by impaired head-to-tail coupling that eventually might induce sperm decapitation on the specific conditions of in vivo fertilisation. As subfertility in haplo-deficient ODF1 male mice could not be diagnosed by semen analysis, it seems to be a paradigm for unexplained infertility that is a frequent diagnosis for male fertility impairment in humans.

SPATC 1L maintains the integrity of the sperm head‐tail junction

“…However, the roles of PKA in spermatogenic cell centrioles and flagellar basal bodies during sperm development have not been elucidated, despite the fact that PKA is known for its roles in sperm capacitation [21]. Acephaly in sperm, an abnormality that represents a type of teratozoospermia, is associated with some of the male infertility cases [12] and has been linked to loss of function of several genes [31][32][33][34][35][36]. It is well known that PKA is activated by cAMP binding to the R subunit.…”

“…The CRISPR/Cas9 genome editing method is advantageous in this context, because we were able to observe the phenotype of KO mice using founder mice with a bi-allele deletion. Acephaly in sperm, an abnormality that represents a type of teratozoospermia, is associated with some of the male infertility cases [12] and has been linked to loss of function of several genes [31][32][33][34][35][36]. They include genes encoding protease serine 21 (PRSS21), ornithine decarboxylase antizyme 3 (OAZ3), outer dense fiber 1 (ODF1), Sad1 and UNC84 domain containing 5 (SUN5), and spermatogenesis associated 6 (SPATA6).…”

Headless spermatozoa in infertile men

“…However, family clustering and syndrome homogeneity exist (Baccetti, Burrini, Collodel, Piomboni, & Renieri, ; Baccetti et al., ); there may be a genetic basis. Some known proteins, such as outer dense fibres (ODFs) and ornithine decarboxylase antizymes (OAZs), have played important roles (Tokuhiro et al., ; Yang, Grzmil, Meinhardt, & Hoyer‐Fender, ; Yang et al., ), but other potential causative genes and functional proteins remain unknown.…”

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

“…85 Haplo-deficiency of ODF1 ( Odf1 +/- ) in mouse sperm causes relaxation of head-to-tail linkage and severe male subfertility. 86 Linking of ODF1 to microtubules might occur via ODF1/SPAG5/SPAG4 (axoneme-binding proteins) interaction and to mitochondria via ODF1/KLC3 (kinesin light chain) interaction. 85 …”