TSGA10 is a novel candidate gene associated with acephalic spermatozoa

Abstract

Acephalic spermatozoa is a rare teratozoospermia associated with male infertility. However, the pathogenesis of this disorder remains unclear. Here, we report a 27 years old infertile male from a consanguineous family, who presented with 99% headless sperm in his ejaculate. Electron microscopic and immunofluorescence analysis suggested breakage at the midpiece of the patient's sperm cells. Subsequent whole-exome sequencing analysis identified a homozygous deletion within TSGA10 (c.211delG; p.A71Hfs*12), which resulted in the production of truncated TSGA10 protein. TSGA10 is a testis-specific protein that localized to the midpiece in the spermatozoa of a normal control; however, immunostaining failed to detect TSGA10 protein in the patient's sperm. Western blot analysis also showed complete absence of TSGA10 protein in the patient. One cycle of in vitro fertilization-assisted reproduction was conducted, but pregnancy was not achieved after embryo transfer, possibly due to poor embryo quality. Therefore, we speculate that the presence of rare sequence variants within TSGA10 may be associated with acephalic spermatozoa in humans.

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

“…No significant differences were observed between semen parameters of the two patients harboring PMFBP1 mutations compared to those of patients with mutations in other genes ( SUN5 , TSGA10, and BRDT ) and in the PMFBP1 gene in the recent published work . However, sperm with round or amorphous heads were found in the ejaculate of our two patients, in addition to low sperm concentration (Table ).…”

“…Previous studies found that SUN5 mutations cause breakage between the head and mid-piece of the tail, 6 while TSGA10 mutations lead to breaks within the mid-piece region. 11 Based on our findings in the present study using immunostaining with to connect the coupling apparatus and the caudal portion of the sperm head. 19 In the present study, we also examined the expression and localization of SUN5 and TSGA10 in the acephalic sperm from patients harboring PMFBP1 mutations.…”

“…Another point of consideration is the sperm break site. Previous studies found that SUN5 mutations cause breakage between the head and mid‐piece of the tail, while TSGA10 mutations lead to breaks within the mid‐piece region . Based on our findings in the present study using immunostaining with the mitochondria marker COXIV, the break site of acephalic sperm lacking PMFBP1 may be in the neck region.…”

“…Previous studies showed that patients with acephalic spermatozoa harboring SUN5 mutations have a good pregnancy outcome after ICSI treatment . However, pregnancy was not achieved after embryo transfer in the woman whose husband harbors a TSGA10 mutation . In this study, the two patients and their respective wives did not receive support from assisted reproductive technology.…”

“…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.…”