Genetic contribution of SUN5 mutations to acephalic spermatozoa in Fujian China

Sha, Yanwei; Xu, Xiaohui; Ji, Zhiyong; Lin, Shaobin; Wang, Xu; Qiu, Pingping; Zhou, Yulin; Mei, Libin; Su, Zhiying; Li, Lin; Li, Ping

doi:10.1016/j.gene.2018.01.035

Cited by 40 publications

(38 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both nonsense and frameshift variations result in truncated SUN5 proteins, the functions of which were lost [27]. Meanwhile, a mutated SUN5 gene can reduce the expression of outer dense fiber 1 (ODF1) protein, which may be the cause of the misarranged structure of the mitochondrial sheath [35]. us, homozygous and/or compound heterozygous variations of the SUN5 gene can result in the formation of primary AS defects.…”

Section: As Defects Subtype II and Related Genesmentioning

confidence: 99%

Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes

Nie¹,

Tang²,

Qin³

2020

BioMed Research International

View full text Add to dashboard Cite

This review analyses the genetic mechanisms of acephalic spermatozoa (AS) defects, which are associated with primary infertility in men. Several target genes of headless sperms have been identified but intracytoplasmic sperm injection (ICSI) outcomes are complex. Based on electron microscopic observations, broken points of the sperm neck are AS defects that are based on various genes that can be classified into three subtypes: HOOK1, SUN5, and PMFBP1 genes of subtype II; TSGA10 and BRDT genes of subgroup III, while the genetic mechanism(s) and aetiology of AS defects of subtype I have not been described and remain to be explored. Interestingly, all AS sperm of subtype II achieved better ICSI outcomes than other subtypes, resulting in clinical pregnancies and live births. For subtype III, the failure of clinical pregnancy can be explained by the defects of paternal centrioles that arrest embryonic development; for subtype I, this was due to a lack of a distal centriole. Consequently, the embryo quality and potential ICSI results of AS defects can be predicted by the subtypes of AS defects. However, this conclusion with regard to ICSI outcomes based on subtypes still needs further research, while the existence of quality of oocyte and implantation failure in women cannot be ignored.

show abstract

Section: As Defects Subtype II and Related Genesmentioning

confidence: 99%

Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes

Nie¹,

Tang²,

Qin³

2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…6,10 Different studies suggested that SUN5 mutations can account for approximately 33% to 47% of all affected cases. 6,9 Subsequent studies found that mutations in TSGA10 and BRDT were also associated with acephalic spermatozoa 11,12 ; however, the cause of acephalic spermatozoa in over half of patients is still unknown, 6,9,11 indicating other genes and mutations may be involved in disease pathology.…”

Section: Introductionmentioning

confidence: 99%

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Sha

Wang

et al. 2018

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic spermatozoa is one of the diseases causing primary infertility. However, the causes underlying over half of affected cases remain unclear. Here, we report by whole‐exome sequencing the identification of homozygous and compound heterozygous truncating mutations in PMFBP1 of two unrelated individuals with acephalic spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse testis. Furthermore, immunofluorescence staining in sperm from a normal control showed that PMFBP1 localizes to the head‐flagella junction region, and the absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In addition, we generated Pmfbp1 knock‐out (KO) mice, which we found recapitulate the acephalic sperm phenotype. Label‐free quantitative proteomic analysis of testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins, respectively, increased or decreased in sperm from KO mice compared to that found in control mice. Gene ontology analysis indicates that the biological process of Golgi vesicle transport was the most highly enriched in differentially expressed proteins, indicating process defects related to Golgi complex function may disturb formation of the head‐neck junction. Collectively, our data indicate that PMFBP1 is necessary for sperm morphology in both humans and mice, and that biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa.

show abstract

“…16 In previous studies, we have reported that the mutations in SUN5, TSGA10 and BRDT may result in acephalic spermatozoa in human. 13,14,23 These results suggest that acephalic spermatozoa could be caused by single genetic mutations.…”

Section: Discussionmentioning

confidence: 80%

“…Deletion of SUN5 did not impact the formation of HTCA, but HTCA was separated from implantation fossa at the beginning of sperm deformation, resulting in acephalic spermatozoa. 23,29 Zhu et al reported that 72.00% (18/25) of their acephalic spermatozoa cohort is caused by SUN5 and PMFBP1 mutations, suggesting that other gene mutations are also involved in the development of acephalic spermatozoa. 16 In previous studies, we have reported that the mutations in SUN5, TSGA10 and BRDT may result in acephalic spermatozoa in human.…”

Section: Discussionmentioning

confidence: 99%