Synaptonemal complex defects in a man with nonobstructive azoospermia

Abstract

Objective: We have previously demonstrated an association between decreased recombination and nondisjunction in sperm. The aim of this study was to analyze early stages of meiosis in infertile men to determine if any abnormalities in chromosome pairing or recombination could be discerned. Design:The stages of meiotic prophase, extent of chromosome pairing and the number of recombination foci were compared in a man with nonobstructive azoospermia and controls. Materials and Methods: Immunofluorescence methods were used to identify the synaptonemal complex in various stages of prophase. Antibodies were used to identify the synaptonemal complex (SCP1/SCP3), the centromere (CREST) and sites of recombination (MLH1). Results: Only 36 meiotic spreads could be recovered from the infertile man with nonobstructive azoospermia compared to hundreds of spreads available from controls. One-third of his cells were delayed in the early stages of meiosis (zygotene). The infertile man had a greatly reduced frequency of recombination with a mean of only 33.4% foci (range 1–67) compared to a mean of 50 foci (range 36–67) in controls. Also 34.8% of pachytene cells had at least one bivalent with no recombinant foci and 52.2% of cells had unpaired chromosome regions. Lack of chromosome pairing is known to cause meiotic arrest in humans. Conclusion:This is the first infertile man identified to have an arrest in meiosis because of an error in the processing of recombination foci or a defect in SCP 1 leading to incomplete chromosome pairing.