Abnormal synapses and recombination in an azoospermic male carrier of a reciprocal translocation t(1;21)

Objective

To study the meiotic abnormalities during prophase I in an azoospermic man with t(1;21) reciprocal translocation.

Design

Analysis of synapses, recombination, and transcription inactivation in a testicular biopsy sample.

Setting

Research laboratory.

Patient(s)

One azoospermic patient with t(1;21) and five men with normal spermatogenesis.

Intervention(s)

Immunostaining for SCP3, MLH1, and γ-H2AX/BRCA1 was performed on biopsy to identify synapses, recombination, and transcriptional inactivation, respectively.

Main Outcome Measure(s)

Synapses, recombination, and transcriptional inactivation in meiosis I.

Result(s)

The t(1;21) carrier had a larger number of synaptonemal complexes with gaps and a lower rate (46%) of XY pairs with MLH1 foci than the controls (78%). The asynapsed quadrivalents, which were often associated with an XY body (84%), were frequently observed (96%) in pachytene cells of the translocation carrier. The variant histone γ-H2AX and BRCA1 proteins were found to be located at the asynapsed quadrivalents.

Conclusion(s)

These results suggest that impaired synaptic integrity of translocated chromosomes may affect synapses, recombination frequency of XY pairs, and transcriptional activation of asynapsed areas, and consequently may impair fertility in men.

Key Words: Chromosomal translocation, azoospermia, meiosis, synaptonemal complex (SC), recombination, transcriptional inactivation