Globozoospermia: A Case Report and Systematic Review of Literature

Abstract

Purpose Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globozoospermic patient with a new, not yet described mutation of the DPY19L2 gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormalities to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical management of these patients. Materials and Methods We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: “globozoospermia”, “round-headed spermatozoa”, “round head spermatozoa”, “intracytoplasmic sperm injection”, “ICSI”, “offspring”, “child health”, “assisted reproductive technique outcome”. All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the “Cambridge Quality Checklists”. Results The main genes involved in the pathogenesis of globozoospermia are DPY19L2 , SPATA16 , PICK1 , GGN , SPACA1 , ZPBP , CCDC62 , and CCNB3 genes. Other genes could also play a role. These include C2CD6 , C7orf61 , CCIN , DNH17 , DNH6 , PIWIL4 , and CHPT1 . Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplasmic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring. Conclusions This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.

Testis-specific gene C7orf61 is involved in mouse sperm–egg fusion

“…Another study also suggested a critical role of C7orf61 in the pathogenesis of globozoospermia; mutations in C7orf61 ((c.259del; p.(Glu87Argfs * 46)) were reported in patients with globozoospermia [5,[15][16][17]. Consistent with these ndings, the expression of C7orf61 mRNA sharply increased in the fourth postnatal week until adulthood in this study.…”

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence

“…Notwithstanding the evidence reported above, as previously exposed, the gene most frequently involved in the pathogenesis of globozoospermia is DPY19L2 [5,113,143,145]. In particular, it is mutated in about 80% of patients with globozoospermia type I [143], and the mutation most frequently described is the deletion of the entire gene, which has been reported to have a prevalence ranging from 22.2% [156,157].…”

“…The sperm without acrosome is unable to go through the zona pellucida, often inducing fertilisation failures even when ICSI is attempted. In particular, the mean fertilisation rate for patients with total globozoospermia is 24.1%, whilst the fertilisation rate is higher in patients with partial globozoospermia (61%) [145]. The association of ICSI with assisted oocyte activation significantly improved the mean fertilisation rate (58.8% ± 23.7%) [144,145].…”

The Genetic and Genomic Landscape of Human Reproductive Disorders: An Overview with Our Experience

“…Genetic defects leading to morphological defects (teratozoospermia) of sperms, in particular, round-headed sperm/sperm without acrosome (globozoospermia) are DPY19L2, SPACA1, SPATA16, PICK1, GGN, AURKC, FAM71F1, GOPC, HRB, CSNK2A2, BS, ZPBP1, CCDC62, CCNB3, etc. [88][89][90][91][92][93] Other genes that could also play a role in globozoospermia are CFAP47, C2CD6, C7orf61, CCIN, DNH17, DNH6, PIWIL4, CHPT1, etc. 92,93 Macrozoospermia (large-headed spermatozoa) is characterized by the presence of large-headed multi-flagellar spermatozoa.…”