CCIN mutations cause teratozoospermia and male infertility

During mammalian spermatogenesis, dramatic shape changes
occur as sperm cells mature into sperm.
The morphology of mature sperm is one of the important indicators of male fertility, and clinical evidence suggests that dysmorphic sperm (teratospermia) have a reduced
fertilization capacity.
Although previous studies have identified many genes associated with teratozoospermia, the cause remains unclear
in most affected men.

Yong Fan et al.
identified a new homozygous mutation and a complex heterozygous mutation CCIN in two families
with male infertility.
Ultrastructural analysis of the patient's sperm showed that the sperm malformation associated with CCIN deficiency was similar to type II globulospermia, with abnormal nuclear and acrosome morphology, and excessive
sperm cytoplasmic residue.
The patient phenotype was successfully reproduced in a mouse model with disease-associated variations, confirming the fundamental role of CCIN in male fertility
.

Both in vitro and in vivo studies have shown that CCIN mutations impair the stability of the Calicin protein, resulting in a significant decrease
in the levels of Calicin in mutant sperm.
The lack of Calicin interferes with the formation of sperm nuclei and the biogenesis of the acrosome, which ultimately leads to sperm head malformations
during spermatogenesis.

By further exploring its intrinsic mechanism CCIN in mutant male infertility, the team found that all mutated sperm from human patients and mice could not adhere to
the bands of the egg.
The use of intracytoplasmic sperm injection (ICSI) successfully overcame the defect caused by the fertilization defect CCIN mutation and made the mutated mice with two pairs of CCIN variants have healthy offspring
.

All in all, this work provides an understanding of CCIN shaping
in the sperm head.
These findings will facilitate the genetic diagnosis of teratozoospermia and provide potential guidance
for appropriate assisted reproductive treatment.