Human male infertility is often related to chromosome abnormalities. In chromosomally normal infertile males, the rates of chromosome 21 and sex chromosome disomy in spermatozoa are increased. Higher incidences of trisomy 21 (seldom of paternal origin) and sex chromosome aneuploidy are also found. XXY and XYY patients produce increased numbers of XY, XX and YY spermatozoa, indicating an increased risk of production of XXY, XYY and XXX individuals. Since XXYs can reproduce using intracytoplasmic sperm injection (ICSI), this could explain the slight increase of sex chromosome anomalies in ICSI series. Carriers of structural reorganizations produce unbalanced spermatozoa, and risk having children with duplications and/or deficiencies. In some cases, this risk is considerably lower or higher than average. These patients also show increased diploidy, and a higher risk of producing diandric triploids. Meiotic disorders are frequent in infertile males, and increase with severe oligoasthenozoospemia (OA) and/or high follicle stimulating hormone (FSH) concentrations. These patients produce spermatozoa with autosomal and sex chromosome disomies, and diploid spermatozoa. Their contribution to recurrent abortion depends on the production of trisomies, monosomies and of triploids. The most frequent sperm chromosome anomaly in infertile males is diploidy, originated by either meiotic mutations or by a compromised testicular environment.

Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrd.1120100210

Zona‐free hamster eggs: Their use in assessing fertilizing capacity and examining chromosomes of human spermatozoa

Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization

The chromosome constitution of human spermatozoa was determined after injecting individual spermatozoa into mouse oocytes. Of a total 279 eggs arrested at first cleavage metaphase, 200 (71.7%) were suitable for the analysis of sperm chromosomes. Incidences of spermatozoa with numerical and structural chromosome aberrations were 1.3 and 6.9% respectively in spermatozoa with normal head morphology, showing values comparable with those found in previous studies using the hamster oocyte-human sperm fusion system. The ratio of X- to Y-bearing spermatozoa did not differ significantly from the expected 1:1 ratio. The incidence of structural chromosome aberrations was about four times higher in spermatozoa with amorphous, round and elongated heads (26.1%) than in those with morphologically normal heads, whereas the incidence of aneuploidy was not significantly different between the two groups. No increase in chromosome aberrations was found in spermatozoa with large heads. The same was true for spermatozoa with small heads. Although the sample size used in this study is rather small, the results nevertheless indicate that some morphological abnormalities in the sperm heads are associated with their chromosome defects.

Andrology: Analysis of chromosome constitution of human spermatozoa with normal and aberrant head morphologies after injection into mouse oocytes

We review the data pertinent to the hypothesis we proposed three decades ago, that all embryos that survive gestation as women with Turner syndrome and have an ostensibly non-mosaic 45,X karyotype, actually are cryptic mosaics for a “rescue line” that includes a viable karyotype. Reanalysis of the prevalence and frequency of 45,X in available data on spontaneous abortuses, and livebirths, confirms prior estimates that 1 % to 1.5 % of all recognizable pregnancies start as an apparent non-mosaic 45,X but about 99 % do not survive gestation. From the rates of 45,X in early embryos, which are notably higher than the inferred rate of gametes hypohaploid for a sex chromosome, as well as the negative maternal age association with 45,X of maternal origin we deduce, in agreement with but on independent grounds from Hall et al. (2006), that a very large proportion of 45,X embryos acquired their 45,X line after fertilization. Results of a search for mosaic cell lines in patients with “Turner syndrome” in several reports indicate that not only does the detection rate of a mosaic line depend upon the number and sensitivity of the markers used, and the number of different tissues examined, but also upon the severity of the phenotype of those cases studied, and the number of cells karyotyped initially. Such factors may explain variation in the extent of detected “cryptic” mosaicism in 45,X individuals (currently at least 50 %). We note a report by Urbach and Benvenitsy (2009) of a gene necessary for placental function, PSF2RA, which lies in the pseudoautosomal-one region of the X and Y chromosomes. Deletion of such a gene could account for the high embryonic lethality in 45,X conceptions, and a rescue line in the placenta could account for embryonic and fetal survival of those cases in which a cryptic mosaic line cannot be found in the usual studies of blood and other tissues from affected individuals. Our primary conclusions are 1) all 45,X individuals with Turner syndrome are cryptic mosaics, 2) absence of the X chromosome in 45,X embryos is caused primarily by mitotic factors, and 3) the placenta is a strong candidate for the location of the rescue line in apparently non-mosaic 45,X individuals.

Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss

A detailed technique is described for obtaining preparations of the chromosome complements of human sperm by fertilization of hamster eggs and analysis of the male pronucleus. Some of the more difficult aspects and important steps are emphasized. Technical data from 17 consecutive experiments are presented to provide an estimate of the number of karyotypes which can be obtained in an experiment.

Martin Rh

Papers

A detailed method for obtaining preparations of human sperm chromosomes.