title: Nuclear volume differences between balanced and unbalanced spermatozoa in chromosomal translocation carriers.
abstract: While chromosomal translocations are usually associated with a normal phenotype, they can still cause male infertility as well as recurrent miscarriages and fetal malformations related to their transmission in an unbalanced state. The distinction between balanced and unbalanced spermatozoa on morphological criteria is still unfeasible. However, we previously showed that: i) spermatozoa with an unbalanced content have a higher rate of DNA fragmentation; and ii) that density gradient centrifugation partially separates balanced from unbalanced sperm cells. We hypothesized that a chromosomal imbalance could alter the fine spermatic nuclear architecture and consequently the condensation of DNA, thus modifying normal sperm density. Spermatic nuclear volumes in four translocation carriers were analyzed using confocal microscopy. Secondarily, FISH analysis was used to establish the segregation mode of each spermatozoon. We found the average spermatic nuclei size to be higher among unbalanced spermatozoa in all patients but one. All the unbalanced modes were associated with larger nuclei in two patients, while this was the case for the 3:1 mode only in the other two, suggesting an abnormal condensation. This could be the first step in elaborating a procedure to completely eliminate unbalanced spermatozoa from semen prior to in vitro fertilization.
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France. Electronic address: alexandrerouen@gmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Rouen
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France.
authors.forename: Alinoë
authors.initials: A
authors.lastname: Lavillaureix
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Hyon
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France.
authors.forename: Solveig
authors.initials: S
authors.lastname: Heide
authors.affiliation: Ecole Normale Supérieure, Département de Chimie, Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolécules, UMR7203, 25 rue Lhomond, 75231 Paris Cedex 05, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Clède
authors.affiliation: Service de Médecine de la Reproduction, Clinique des Bluets, 4 rue Lasson, 75571 Paris Cedex 12, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Balet
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Kott
authors.affiliation: Laboratoire Drouot, Clinique des Bluets, 4 rue Lasson, 75571 Paris Cedex 12, France.
authors.forename: Nino Guy
authors.initials: NG
authors.lastname: Cassuto
authors.affiliation: Service de Génétique et Embryologie Médicales, Hôpital Armand-Trousseau, AP-HP, Unité INSERM U933, 26 Avenue du Dr Arnold Netter, Paris 75012, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology; D000328:Adult; D022981:Allelic Imbalance; D053145:Cell Nucleus Size; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020090:Chromosome Segregation; D005191:Family Characteristics; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D005602:France; D006579:Heterozygote; D006801:Humans; D021621:Imaging, Three-Dimensional; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000209:etiology; D007364:Intercalating Agents / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*; D014178:Translocation, Genetic
chemical_list: D005456:Fluorescent Dyes; D007364:Intercalating Agents
keywords: chromosomal translocations; confocal microscopy; infertility; spermatic DNA