Meiotic behaviour and sperm aneuploidy in an infertile man with a mosaic 45,X/46,XY karyotype

Abstract

The meiotic behaviour of the germ cells in 45,X/46,XY men has not been extensively studied. This study investigated the meiotic events and sperm aneuploidy in an azoospermic man with a 45,X/46,XY (50/50) mosaic karyotype to better understand the fate of the 45,X cells and the production of chromosomally abnormal spermatozoa. Combining immunofluorescence techniques and fluorescence in-situ hybridization, meiotic recombination, synapsis, meiotic sex chromosome inactivation (MSCI) and configuration were analysed, as well as sperm aneuploidy in the patient and 10 normal, fertile men. Despite the 50:50 somatic mosaicism in the patient, 25% of pachytene cells analysed were 45,X. Furthermore, 63% of pachytene cells were 46,XY with paired sex chromosomes, and 12% were 46,XY with unpaired sex chromosomes, which displayed abnormal MCSI patterns. Although the patient's testicular spermatozoa showed increased aneuploidy, the majority were of normal constitution. The X:Y sperm ratio was significantly increased compared with the controls (P < 0.001), which may indicate that some 45,X cells gave rise to X-bearing spermatozoa. The findings provide insight into the fate of 45,X/46,XY cells in meiosis, supporting the hypothesis that stringent checkpoints ensure the favourable production of spermatozoa with normal chromosomal constitution despite an individual's abnormal karyotype.

Localization of the <b><i>SRY</i></b> Gene on Chromosome 3 in a Patient with Azoospermia and a Complex Karyotype 45,X/46,X,i(Y)(q10)/46,XX/ 47,XX,i(Y)(q10)

“…The sperm aneuploidy rate in a male with an XO/XYY karyotype was almost similar to that seen in controls, whereas in another study of a Klinefelter male with an XXY/XXXY/XY chromosome composition, the number of hyperhaploid sperm was greater than in a normal male [Kruse et al, 1998;Dale et al, 2002;Ren et al, 2015]. Thus, if sperm is available in the testes of the patient, ART using surgical sperm retrieval, like percutaneous epididymal or testicular sperm aspiration (PESA or TESA), followed by intracytoplasmic sperm injection (ICSI) can help men with a mosaic karyotype.…”

45,X/46,XY Mosaicism and Normozoospermia in a Patient with Male Phenotype

“…The increased rate of nullisomic sperm is remarkable as this has been described in other cases of 45,X/46, XY mosaicism [26, 27] as well as in infertile males with other mosaic states of gonosomes [28]. However, it has not been found in infertile males with abnormal semen parameters and with normal karyotypes [20] with the possible exception of men with hidden mosaicism and deletions of the long arm of the Y chromosome [26].…”

A Rare Cause of Male Infertility: 45,X/46,XY Mosaicism

“…In same study, although their case displayed increased rates of sex chromosome aneuploidy, the authors suggest that infertile men with abnormal sex chromosome karyotypes and high levels of mosaicism may nevertheless produce spermatozoa that are primarily normal in chromosomal constitution. Because 46,XY cells have the capacity of normal meiotic division [22]. In our study, karyotype analysis was not performed in germ cells.…”