Presence of an extra chromosome alters meiotic double-stranded break repair dynamics and MLH1 foci distribution in human oocytes

Studies performed on human trisomic 21 oocytes have revealed that during meiosis, the three homologues 21 synapse and, in some cases, achieve what looks like a trivalent. This implies that meiotic recombinationtakes place among the three homologous chromosomes21, and to some extent, crossoversform between them. To see how meiotic recombinationis in the presence of an extra chromosome 21, we analyzed the distribution of three recombinationmarkers (γH2AX, RPA, and MLH1) on trisomic 21 oocytes at pachynema and, in particular, on chromosomes 21. Results clearly show how the presence of an extra chromosome 21alters meiotic recombinationprogression, leading to the presence of a higher number of early recombinationmarkers at pachynema. Moreover, the distribution on these chromosomes 21of some of these markers is different in aneuploid oocytes. Finally, there is a substantial increase in the number of MLH1foci, a marker of most crossoversin mammals, which is related to the number of synapsed chromosomes in pachynema. Thus, bivalents 21 had fewer MLH1foci than partial or total trivalents, suggesting a close relationship between synapsisand crossoverdesignation. All of the data presented suggest that the presence of an extra chromosome alters meiotic recombinationglobally in aneuploid human oocytes.