Chronology of meiosis & synaptonemal complex abnormalities in normal & abnormal spermatogenesis.

BACKGROUND & OBJECTIVES The study was taken up to define criteria of normality for meiosis by assessing the frequency of meiotic prophase cell types, the frequency of pachytene substage in normal and abnormal spermatogenesis and to determine what synaptonemal complex. METHODS A quantitative and qualitative analysis of the first meiotic prophase was performed in 10 patients presenting with non-obstructive infertility and 10 controls, using dual colour immunocytochemistry with SCP3 and BRCA1 which visualise axial elements and synaptonemal complexes (SC). The respective frequencies of the leptotene, zygotene and pachytene stages as well as the frequencies of the four substages of pachytene were evaluated. The frequencies of the main types of meiotic abnormalities at pachytene were also assessed. RESULTS The frequencies of leptotene and zygotene stages were significantly higher in patients (7.95 and 9.75%) than in controls (2.30 and 1.45%), whereas the frequency of pachytene was significantly higher in controls than in patients (96.25 vs. 75.30%). Detailed analysis of the sex chromosomes revealed that the controls showed a presence of late pachytene substages (P3 + P4 = 64.40%), whereas the patients showed a early pachytene substages (P1 + P2 = 63.40%). From these results, a new index was defined to evaluate spermatogenesis: the Pachytene Index, or PI (PI = P1 + P2 / P1 + P2 + P3 + P4). The same abnormalities (asynapsis, fragmented SC, dotted SC, thin SC) were observed in controls and in patients, but with different frequencies. The most frequent abnormality was fragmented SC, with a significant difference between patients and controls (15.28 vs. 9.74%). There was a significant difference between patients and controls for the frequency of asynapsed nuclei (7.97 vs. 2.95%) while the difference in other abnormalities were not significant. INTERPRETATION & CONCLUSION The accumulation of early primary spermatocytes is an indication that progression of meiosis is defective in spermatogenesis failures. The value of the PI less than 0.50 indicates that the kinetic of meiosis is normal at pachytene. There is no normal spermatogenesis when the frequency of one or several SC abnormalities is significantly higher than in controls and/ or when the PI is more than 0.50.