Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men

Andrea Enguita-Marruedo, Esther Sleddens-Linkels, Marja Ooms, Vera de Geus, Martina Wilke, Eric Blom, Gert R Dohle, Leendert H J Looijenga, Wiggert van Cappellen, Esther B Baart, Willy M Baarends

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To establish which meiotic checkpoints are activated in males with severe spermatogenic impairment to improve phenotypic characterization of meiotic defects.

DESIGN: Retrospective observational study.

SETTING: University medical center research laboratory and andrology clinic.

PATIENT(S): Forty-eight patients with confirmed spermatogenic impairment (Johnsen scores 3-6) and 15 controls (Johnsen score 10).

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Quantitative assessment of immunofluorescent analyses of specific markers to determine meiotic entry, chromosome pairing, progression of DNA double-strand break repair, crossover formation, formation of meiotic metaphases, metaphase arrest, and spermatid formation, resulting in a novel classification of human meiotic arrest types.

RESULT(S): Complete metaphase arrest was observed most frequently (27%), and the patients with the highest frequency of apoptotic metaphases also displayed a reduction in crossover number. Incomplete metaphase arrest was observed in 17% of the patients. Only four patients (8%) displayed a failure to complete meiotic chromosome pairing leading to pachytene arrest. Two new types of meiotic arrest were defined: premetaphase and postmetaphase arrest (15% and 13%, respectively).

CONCLUSION(S): Meiotic arrest in men occurs most frequently at meiotic metaphase. This arrest can be incomplete, resulting in low numbers of spermatids, and often occurs in association with reduced crossover frequency. The phenotyping approach described here provides mechanistic insights to help identify candidate infertility genes and to assess genotype-phenotype correlations in individual cases.

Original languageEnglish
Pages (from-to)1059-1070.e3
JournalFertility and sterility
Volume112
Issue number6
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Apoptosis
  • Azoospermia/congenital
  • Chromosome Pairing
  • DNA Breaks, Double-Stranded
  • Humans
  • Male
  • Metaphase
  • Pachytene Stage
  • Retrospective Studies
  • Spermatogenesis
  • Spermatozoa/pathology
  • Testis/pathology

Fingerprint

Dive into the research topics of 'Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men'. Together they form a unique fingerprint.

Cite this