Sperm cell tails or flagella are crucial for fertility as they are responsible for allowing the sperm to swim to, and fertilise the egg cell. The Fsip2 (Fibrous Sheath-Interacting Protein 2) protein is a component of the fibrous sheath of a sperm cell tail, but there is little understanding of how disruption of its production could contribute to abnormal sperm morphology, which causes infertility. Now, researchers at Guangzhou Women and Children’s Medical Centre, China have identified a mutation in the Fsip2 gene in an infertile man who was known to have multiple defects in his sperm flagella.
'The fibrous sheath covers the tails of sperm found in humans, mice and other species in which fertilisation occurs within the animal’s body,' said Dr Na Li, senior author for the study which was published in the journal Development. 'It offers the sperm tail flexibility and strength, which is necessary for sperm to swim in the dense and sticky medium of the human body before they meet the egg. Interestingly, animals whose sperm swim through water because fertilisation occurs outside of the body, such as fish, either do not have the Fsip2 protein or, at most, a defective version.'
Two mouse models were created to investigate the role of this gene, one with the mutated version of Fsip2 and one with overexpression of it.
The group with the gene mutation showed reductions in sperm motility and viability, as well as the same morphological defects in sperm observed in the patient. Additionally, these mice were sterile. On the other hand, the group overexpressing the gene had sperm with longer tails, and retained their fertility.
Researchers carried out detailed analysis of the mutant mice and their sperm to understand the role of Fsip2. Importantly, they found that Fsip2 modifications led to changes in other proteins. As expected, changes to the fibrous sheath were observed in the mice with the gene mutation, but other important features were also impacted. Proteins involved in function of the mitochondria, which provides the energy to power sperm movement, were affected. Additionally, proteins associated with the acrosomal vesicle – a region of the sperm head which provides components that support entry of the sperm into the egg – showed abnormalities. These details help our understanding of the role of Fsip2 in development of the sperm tail.
This work provides insight into sperm function and development, as well as identifying Fsip2 as a possible target for treating male infertility.