News | Sperm Structure and Fertility: The Role of Cylicins in Sperm Formation



News | Sperm Structure and Fertility: The Role of Cylicins in Sperm Formation


A study published in eLife used CRISPR/Cas9 gene editing to examine the role of cylicins in spermiogenesis and male fertility in mice and humans. Cylicins are important components of sperm-head structure, and their absence causes abnormal sperm morphology and function that can impair fertility.


Sperm moving toward an egg, model before fertilization, 3D rendering_170658162.jpg


The Key Role of Cylicins in Spermiogenesis

Spermiogenesis is the complex process that transforms round spermatids into mature sperm and involves DNA condensation and development of the acrosome and flagellum. It depends on the perinuclear theca (PT), a specialized sperm cytoskeletal structure whose key components include cylicin 1 (Cylc1) and cylicin 2 (Cylc2).


Researchers found that cylicins anchor the acrosome to the nuclear membrane during acrosome formation. Without cylicins, the acrosome separates from the nuclear membrane and sperm-head formation is disrupted. Their absence also causes abnormalities in other structures involved in spermiogenesis, including an excessively elongated manchette and delayed manchette disassembly, which impair sperm maturation.


Evolutionary Analysis and Clinical Relevance

Evolutionary analysis of cylicin genes in mammals showed that Cylc1 and Cylc2 are under purifying selection, although selection pressure on Cylc1 is relatively weak, suggesting some functional redundancy. This may explain why loss of Cylc1 causes subfertility while loss of Cylc2 causes complete infertility. A single functional Cylc2 allele can also partly compensate for the absence of Cylc1.


Human patients with cylicin gene variants showed sperm abnormalities and infertility similar to those seen in mice. The study also noted that some men with heterozygous CYLC2 variants were not completely infertile but had difficulty conceiving naturally.


Significance

By comparing mouse models with human cases, the study provides the first comprehensive account of cylicins' importance in sperm development. Future research may further clarify how cylicin variants affect human infertility and identify new diagnostic and treatment targets for male infertility.


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