Genetic aspects of monomorphic teratozoospermia: a review

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.