無精症之病患精蟲進行減數分裂過程常常(27%)發生減數分裂中期(metaphase)中止
進一步造成無法形成原始精細胞spermatid

Fertil Steril. 2019 Nov 22. pii: S0015-0282(19)31992-2. doi: 10.1016/j.fertnstert.2019.08.004. [Epub ahead of print]

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

Enguita-Marruedo A1, Sleddens-Linkels E1, Ooms M1, de Geus V1, Wilke M2, Blom E2, Dohle GR3, Looijenga LHJ4, van Cappellen W5, Baart EB6, Baarends WM7.

Author information

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.