title: The high frequency of sperm aneuploidy in klinefelter patients and in nonobstructive azoospermia is due to meiotic errors in euploid spermatocytes.
abstract: For nonobstructive azoospermic (NOA) patients with a normal karyotype or  for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection  is associated with an increased aneuploidy risk in offspring. We examined  testicular cells from patients with different azoospermia etiologies to  determine the origin of the aneuploid spermatozoa. The incidence of chromosome  abnormalities was investigated in all types of azoospermia. Four study  subgroups were constituted: Klinefelter patients (group 1), NOA patients with  spermatogenesis failure but a normal karyotype (group 2), obstructive  azoospermic patients with normal spermatogenesis (group 3), and control  patients with normal sperm (group 4). The pachytene stage (in the three  azoospermic groups) and postmeiotic cells (in all groups) were analyzed with  fluorescence in situ hybridization. No aneuploid pachytene spermatocytes were  observed. Postmeiotic aneuploidy rates were higher in the two groups with  spermatogenesis failure (5.3% and 4.0% for groups 1 and 2, respectively) than  in patients with normal spermatogenesis (0.6% for group 3 and group 4).  Whatever the etiology of the azoospermia, the spermatozoa originated from  euploid pachytene spermatocytes. These results strengthen the hypothesis  whereby sperm aneuploidy in both Klinefelter patients and NOA patients with a  normal karyotype results from meiotic abnormalities and not from aneuploid  spermatocytes. The fact that sperm aneuploidy was more frequent when  spermatogenesis was altered suggests a deleterious testicular environment. The  study results also provide arguments for offering preimplantation genetic  diagnosis or prenatal diagnosis when a pregnancy occurs for fathers with NOA  (whatever the karyotype).
authors.affiliation: Laboratoire d'Histologie, Embryologie, Biologie de la Reproduction, Cytogénétique et Génétique Médicale, Hôpital de Poissy St Germain, Poissy, France. fvialard@chi-poissy-st-germain.fr
authors.forename: François
authors.initials: F
authors.lastname: Vialard
authors.forename: Marc
authors.initials: M
authors.lastname: Bailly
authors.forename: Habib
authors.initials: H
authors.lastname: Bouazzi
authors.forename: Martine
authors.initials: M
authors.lastname: Albert
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Pont
authors.forename: Vanda
authors.initials: V
authors.lastname: Mendes
authors.forename: Marianne
authors.initials: M
authors.lastname: Bergere
authors.forename: Denise Molina
authors.initials: DM
authors.lastname: Gomes
authors.forename: Philippe
authors.initials: P
authors.lastname: de Mazancourt
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Selva
mesh_terms: D000328:Adult; D000782:Aneuploidy; D053713:Azoospermia / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007713:Klinefelter Syndrome / Q000235:genetics; D008297:Male; D008540:Meiosis; D008875:Middle Aged; D020554:Sperm Injections, Intracytoplasmic; D013090:Spermatocytes / Q000166:cytology*; D013094:Spermatozoa / Q000002:abnormalities*