Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility

Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.

Genetic pathogenesis of acephalic spermatozoa syndrome:past,present,and future

Acephalic spermatozoa syndrome(ASS)is one of the most severe spermatogenic failures of all infertility in men.The cognition of ASS has experienced a tortuous process.Over the past years,with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies,the unraveling of the genetic causes of spermatogenic failure has become highly active.From these advances,we established a genetic background and made significant progress in the discovery of the genetic causes of ASS.It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome.In this review,we enumerate various technological developments,which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present.Simultaneously,we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present.Furthermore,we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.

Imprinting methylation and assisted reproductive technology

Assisted reproductive technology （ART） is an important treatment for infertile people of reproductive age and is also known as fertility treatment. The processes of ART involves the isolation, handling and culture of early embryos, which may result in alterations in genomic methylation at specific loci and influence the proper establishment and maintenance of genomic imprints. Recent studies have identified an increased incidence of imprinting disorders via ART. In this article, we reviewed that the ART may be prone to induction of imprinting methylation errors during embryonic development. Further studies are necessary to elucidate the safety of ART in this field.