Abstract
A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles (P = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age (P = 0.004, R = −0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality.
Highlights
Infertility affects 10% of American people, but due to the lack of adequate clinical treatment or access to it, many couples fail to get their desired offspring (Royfman et al, 2020)
During our initial characterization of protein levels in the sperm centrioles using quantitative immunofluorescence, we found that immunofluorescence intensity values alone are not sufficiently sensitive and reproducible to detect differences in staining across multiple studies
We found that differential gradient centrifugation of eumorphic sperm results in a pellet enriched for better quality sperm centrioles
Summary
Infertility affects 10% of American people, but due to the lack of adequate clinical treatment or access to it, many couples fail to get their desired offspring (Royfman et al, 2020). One reason infertility treatments fail is deficiencies in identifying the underlying causes of male factor reproductive diseases. Sperm Centriole Quality there is a need to identify novel causes of male infertility and develop an assay to diagnose them (Turner et al, 2020). Centrioles are essential for the sperm’s formation and motility, and the sperm is the sole contributor of centrioles to the zygote (Avidor-Reiss and Fishman, 2019). The spermatid centrioles undergo a unique “Centriole Remodeling,” which results in sperm centrioles having distinct atypical characteristics (Avidor-Reiss, 2018; Leung et al, 2020). The sperm PC has a canonical structure, but a somewhat atypical composition compared to centrioles in other cells. The sperm DC has a dramatically atypical structure and composition compared to centrioles in other cells
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