Meiotic prophase I defects in an oligospermic man with Wolf-Hirschhorn syndrome with ring chromosome 4

Background: Ring chromosomes are often associated with spermatogenetic failure. However, the mechanism is poorly understood. We here reported a single man with severe oligospermia and a ring chromosome 4 with a microdeletion at 4p16.3. Results: Synapsis (as SCP3), recombination (as MLH1) and transcriptional inactivation (as BRCA1) in a testicular biopsy were examined by fluorescence immunostaining. In the oligospermia patient, 35.4% of spermatocytes were in zygotene phase compared with 5.2% in controls. The patient had a significantly reduced recombination frequency with mean of 45.9 MLH1 foci/cell compared with 47.8 in controls. In the patient, chromosome 4 in all pachytene cells displayed loop formation with varying degrees of unpaired regions. BRCA1 localized along asynapsed regions regardless of XY body association. Conclusions: Ring chromosome 4 might affect the progression of meiosis I prophase, synapse formation, and transcriptional activation of asynapsed areas, and impair male fertility.