Genetic aspects of monomorphic teratozoospermia: a review

Abstract

Teratozoospermia is characterized by the presence of spermatozoa with abnormal morphology over 85 % in sperm. When all the spermatozoa display a unique abnormality, teratozoospermia is said to be monomorphic. Two forms of monomorphic teratozoospermia, representing less than 1 % of male infertility, are recognized: macrozoospermia (also called macrocephalic sperm head syndrome) and globozoospermia (also called round-headed sperm syndrome). Macrozoospermia is defined as the presence of a very high percentage of spermatozoa with enlarged head and multiple flagella. Meiotic segregation studies in 30 males revealed that over 90 % of spermatozoa were aneuploid, mainly diploid. Sperm DNA fragmentation studies performed in a few patients showed an increase in DNA fragmentation index compared to fertile men. Four mutations in the AURKC gene, a key player in meiosis and more particularly in spermatogenesis, have been found to be responsible for macrozoospermia. Globozoospermia is characterized by round-headed spermatozoa with an absent acrosome, an aberrant nuclear membrane and midpiece defects. The rate of aneuploidy of various chromosomes in spermatozoa from 26 globozoospermic men was slightly increased compared to fertile men. However, this increase was of the same order as that commonly found in infertile men with altered sperm parameters. The majority of the studies found that globozoospermic males had a sperm DNA fragmentation index higher than in fertile men. Mutations or deletions in three genes, SPATA16, PICK1 and DPY19L2, have been shown to be responsible for globozoospermia. Identification of the genetic causes of macrozoospermia and globozoospermia should help refine diagnosis and treatment of these patients, avoiding long and painful treatments. Elucidating the molecular causes of these defects is of utmost importance as intracytoplasmic sperm injection (ICSI) is very disappointing in these two pathologies.

Expression profile ofPLCζ,PAWP,andTR-KITin association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation

“…The genetic basis of globozoospermia has been a subject of extensive studies and mainly associated with deletion or deficiency of DPY19L2, SPATA16, Spaca1, and PICK1 genes which are thought to be involved in acrosome biogenesis (Elinati et al, 2012;Fujihara et al, 2012;Chianese et al, 2015;De Braekeleer et al, 2015). In this regard, assessment of RNA in spermatozoa has been recommended as it may reveal the historical record of testicular function and spermatogenesis and thereby can be considered as a genetic fingerprint of the individual.…”

“…Only in one case (G12), the expression levels of these transcripts were close to fertile men, but AOA could not result in a good fertilization rate (17%) in this case. Different explanations can be provided for such a case including defective chromatin packaging or increased DNA fragmentation which has been thought to affect fertilization and pregnancy outcome of ICSI oocytes (De-Braekeleer et al, 2015;Hosseinifar et al, 2015). Yassine et al (2015) recently demonstrated that in globozoospermic mice and humans with deletion of DPY19L2, sperm devoid of an acrosome has altered genomic packaging and increased DNA damage which can compromise ICSI outcomes (Yassine et al, 2015).…”

Aide à l’activation ovocytaire

“…La globozoospermie (spermatozoïdes à tête ronde) est une forme de tératozoospermie monomorphe relativement rare avec une incidence inférieure à 0,1 % chez les hommes infertiles, essentiellement caractérisée par des spermatozoïdes à tête ronde dépourvus d'acrosome 2 . Des mutations ou des délétions dans trois gènes, SPATA16 (spermatogenesis-associated protein 16), PICK1 (qui code une protéine interagissant avec la protéine kinase Cα) et DPY19L2 (dpy-19-like 2), ont été retrouvées chez des patients globozoospermiques [19]. De façon intéressante, PLCζ est absente ou très diminuée dans les spermatozoïdes des patients globozoospermiques porteurs d'une anomalie de DPY19L2 [20].…”

Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia

“…It is characterized by the presence of spermatozoa with abnormal morphology in over 85% in sperm (De Braekeleer et al, 2015). These abnormalities may include heads that are large, small, tapered, or pyriform or tails that are abnormally shaped.…”

“…Meanwhile, Kusz-Zamelczyk et al (2013) were the first to describe the association between NANOS1 gene mutations with human severe oligoasthenoteratozoospermia. Recent reports also suggest that mutations or deletions in AURKC, SPATA16, PICK1, and DPY19L2 are responsible for teratozoospermia (De Braekeleer et al, 2015). However, the genomic or gene expression variation contributing to teratozoospermia is still unknown.…”