Sperm with fibrous sheath dysplasia and anomalies in head-neck junction: focus on centriole and centrin 1

Abstract

Spermatozoa with a rare combination of two monomorphic sperm defects, dysplasia of the fibrous sheath (DFS) and alterations in head-mid-piece junction were analysed. The main focus was to explore the status of the centriole, a key organisation during fertilisation, using the centrin 1, a calcium-binding protein linked to this structure. The sperm quality was examined by light, scanning and transmission electron microscopy (SEM, TEM); immunocytochemistry was performed for tubulin, A-kinase anchor protein 4 (AKAP4) and centrin 1. Spermatozoa showed DFS defect associated with anomalies in head-tail attachment detected by SEM and TEM. Immunolocalisation of tubulin, AKAP4 and centrin 1 confirmed these alterations. Centrin 1 was visible in 67% of spermatozoa (in only 13% centrin localised in a normal position); in the majority of sperm centrin 1's location was altered, sometimes bent; often four spots, indicating the presence of two implantation fossae, were detected. At the centriolar level, immunoreactive fragments, frequently invading the entire short and thick tail, were observed. Centrin 1 is an essential component of the spermatozoa connecting piece and plays a role in centrosome dynamics during sperm morphogenesis and in zygotes and early embryos during spindle assembly. It is important to shed light on these rare conditions in order to better manage the patients during assisted reproductive technology.

The Role of Sperm Centrioles in Human Reproduction – The Known and the Unknown

“…Microscopy of dysplastic sperm reveals an increased and disorganized fibrous sheath with disruption of the underlying axoneme (Chemes et al, 1987a). Immunofluorescence with the centriolar protein Centrin-1 shows frequent abnormal positioning of the centrioles, sometimes with duplication, resulting in two nucleus-implantation sites (Moretti et al, 2017). Initial attempts at ICSI with dysplastic sperm were unsuccessful at achieving pregnancy, due to failure of either fertilization or embryo development (Chemes and Rawe, 2003).…”

Loss‐of‐function mutations in centrosomal protein 112 is associated with human acephalic spermatozoa phenotype

“…Dysfunctional sperm centrioles were viewed as one trigger for the development of acephalic spermatozoa . Moretti et al proved that abnormal expression of centrin 1, one of centriole protein, may take part in fibrous sheath dysplasia, anomalies in head‐neck junction and globozoospermia . Our previous work has shown that homozygous mutation in centrosomal protein 135 (CEP135) may associate with multiple morphological abnormalities of the sperm flagella .…”

“…19 Moretti et al proved that abnormal expression of centrin 1, one of centriole protein, may take part in fibrous sheath dysplasia, anomalies in head-neck junction and globozoospermia. 20,21 Our previous work has shown that homozygous mutation in centrosomal protein 135 (CEP135) may associate with multiple morphological abnormalities of the sperm flagella. 22 All of these studies suggest that CEPs play an important role in maintaining normal sperm morphology and function.…”

Ultrastructural Sperm Flagellum Defects in a Patient With CCDC39 Compound Heterozygous Mutations and Primary Ciliary Dyskinesia/Situs Viscerum Inversus

“…It is mainly ascribed to flagella abnormalities, leading to sperm immotility (Gunes et al, 2018). Transmission electron microscopy (TEM) analysis has documented a number of ultrastructural defects at the sperm level, such as dynein arm deficiency (Kordus et al, 2008), abnormal connecting pieces, shortened mid pieces with attenuated mitochondria sheaths, poorly developed annulus, abnormal outer dense fibers, axonema missing the two central microtubules (Yokota et al, 1993;McLachlan et al, 2012), or dysplasia of the fibrous sheath (Moretti et al, 2017).…”