Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes

Abstract

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.

The missing linker between SUN5 and PMFBP1 in sperm head-tail coupling apparatus

“…One of the unique features of the spermiogenesis is that the Pc moves into the implantation fossa (also recognized as a normal lodging site for the Pc) 30 , 45 , and some proteins may facilitate its attachment to the caudal end of the nucleus. SUN5 directly binds to CENTLEIN, a somatic centrosome protein localized at the proximal ends of the centrioles, but not the centriole distal lumen protein CETN2 (Fig.…”

Patients with acephalic spermatozoa syndrome linked to novel TSGA10/PMFBP1 variants have favorable pregnancy outcomes from intracytoplasmic sperm injection

“…If centrioles fail to establish physical contact with the nucleus, the sperm head and tail develop independently and separate at spermiation through the seminiferous tubules 13 . Loose sperm heads were infrequent in our study, likely because they are usually phagocytosed by Sertoli cells 12,13 . The distal centriole alone is sufficient to grow a complete flagellum, maintaining progressive motility in the ejaculate 14,15 .…”

Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa

“…The HTCA originates from the centrosome and connects the nuclear envelope to the intermediate piece of the flagellum [ 26 ]. SUN5 deficiency is associated with a normal assembly of the HTCA during the early stages of spermiogenesis, but it dissociates from the nuclear envelope in elongated spermatids, causing the detachment of the tail from the head [ 27 ]. The ultrastructural analysis of ejaculated spermatozoa from subject P0504 carrying the identified variant also showed that the HTCA was normally assembled but completely detached from the sperm nuclear envelope.…”