Acephalic spermatozoa and abnormal development of the head–neck attachment: a human syndrome of genetic origin

Abstract

A series of 10 young sterile men with acephalic spermatozoa or abnormal head-mid-piece attachments is presented. Nine of these patients had 75-100% spermatozoa with minute cephalic ends and 0-25% abnormal head-middle piece attachments. Loose heads ranged between 0-35 for each 100 spermatozoa and normal forms were rare. Two patients were brothers. On ultrastructural examination, the head was generally absent and the middle piece was covered by the plasma membrane. When present, heads implanted at abnormal angles on the middle piece. A testicular biopsy showed abnormal spermiogenesis. The implantation fossa was absent and the flagellar anlage developed independently from the nucleus, resulting in abnormal head-middle piece connections. In one patient azoospermia was induced with testosterone to attempt to increase the normal sperm clone during the rebound phenomenon, but all newly formed spermatozoa were acephalic. In another patient with high numbers of defective head-mid-piece connections, microinjections of spermatozoa resulted in four fertilized oocytes, but syngamy and cleavage did not take place, suggesting an abnormal function of the centrioles. The findings indicate that acephalic spermatozoa arise in the testis as the result of an abnormal neck development during spermiogenesis. The familial incidence and the typical phenotype strongly suggest a genetic origin of the syndrome.

Spata6is required for normal assembly of the sperm connecting piece and tight head–tail conjunction

“…These data suggest that SPATA6 is essential for the proper formation of segmented columns during the development of the connecting piece in mice. Interestingly, similar ultrastructral defects (i.e., malformation or partial formation of segmented columns) have been reported in some human infertility patients with acephalic spermatozoa (16,(18)(19)(20)42), suggesting that a similar underlying mechanism is conserved between mice and humans. Segmented columns represent a major structure of the connecting piece, and have been suggested to arise from the so-called "pericentriolar materials" (20,43).…”

“…Extensive ultrastructral studies on humans and animals with acephalic spermatozoa suggest that this condition results from defects in formation of the connecting piece of spermatozoa during late spermiogenesis, including failure for the proximal centrioles to attach normally to the caudal portion of the sperm nuclei, leading to abnormal head-midpiece alignment, or a nuclear defect that interferes with formation of the implantation fossa, the normal lodging site for the sperm proximal centriole (16). Aberrant formation of the connecting piece leads to independent development of the sperm heads and flagella, and eventually these structures become separated within the seminiferous tubules or during their transition through the seminal tract as a consequence of increased instability of the head-midpiece junction (16,18).Several features of the human "acephalic spermatozoa," including its uniform phenotype, origin as a systematic alteration of spermiogenesis, unresponsiveness to hormonal treatment, and familial incidence, suggest a genetic origin of this condition (8,16,(18)(19)(20). Mice lacking Odf1, a gene encoding outer dense fiber protein 1, display fragile sperm connecting pieces in addition to a disorganized mitochondrial sheath and defective outer dense fibers (ODFs) (21).…”

“…Numerous cases of acephalic spermatozoa have been reported in teratozoospermic patients (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In these patients, the major anomaly lies in headless spermatozoa in the ejaculate, and the headless spermatozoa were initially called "pinhead sperm" because the investigators mistakenly regarded the retained cytoplasmic droplets, which are usually attached to the midprincipal piece junction of the flagella, as the heads of reduced size (8,13,14).…”

“…Several features of the human "acephalic spermatozoa," including its uniform phenotype, origin as a systematic alteration of spermiogenesis, unresponsiveness to hormonal treatment, and familial incidence, suggest a genetic origin of this condition (8,16,(18)(19)(20). Mice lacking Odf1, a gene encoding outer dense fiber protein 1, display fragile sperm connecting pieces in addition to a disorganized mitochondrial sheath and defective outer dense fibers (ODFs) (21).…”

“…Extensive ultrastructral studies on humans and animals with acephalic spermatozoa suggest that this condition results from defects in formation of the connecting piece of spermatozoa during late spermiogenesis, including failure for the proximal centrioles to attach normally to the caudal portion of the sperm nuclei, leading to abnormal head-midpiece alignment, or a nuclear defect that interferes with formation of the implantation fossa, the normal lodging site for the sperm proximal centriole (16). Aberrant formation of the connecting piece leads to independent development of the sperm heads and flagella, and eventually these structures become separated within the seminiferous tubules or during their transition through the seminal tract as a consequence of increased instability of the head-midpiece junction (16,18).…”