TY - JOUR
T1 - Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men
AU - Enguita-Marruedo, Andrea
AU - Sleddens-Linkels, Esther
AU - Ooms, Marja
AU - de Geus, Vera
AU - Wilke, Martina
AU - Blom, Eric
AU - Dohle, Gert R
AU - Looijenga, Leendert H J
AU - van Cappellen, Wiggert
AU - Baart, Esther B
AU - Baarends, Willy M
N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Azoospermia/congenital
KW - Chromosome Pairing
KW - DNA Breaks, Double-Stranded
KW - Humans
KW - Male
KW - Metaphase
KW - Pachytene Stage
KW - Retrospective Studies
KW - Spermatogenesis
KW - Spermatozoa/pathology
KW - Testis/pathology
UR - http://www.scopus.com/inward/record.url?scp=85076215316&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2019.08.004
DO - 10.1016/j.fertnstert.2019.08.004
M3 - Article
C2 - 31767154
SN - 0015-0282
VL - 112
SP - 1059-1070.e3
JO - Fertility and sterility
JF - Fertility and sterility
IS - 6
ER -