title: Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks.
abstract: Meiotic recombination is sexually dimorphic in most mammalian species, including humans, but the basis for the male:female differences remains unclear. In the present study, we used cytological methodology to directly compare recombination levels between human males and females, and to examine possible sex-specific differences in upstream events of double-strand break (DSB) formation and synaptic initiation. Specifically, we utilized the DNA mismatch repair protein MLH1 as a marker of recombination events, the RecA homologue RAD51 as a surrogate for DSBs, and the synaptonemal complex proteins SYCP3 and/or SYCP1 to examine synapsis between homologs. Consistent with linkage studies, genome-wide recombination levels were higher in females than in males, and the placement of exchanges varied between the sexes. Subsequent analyses of DSBs and synaptic initiation sites indicated similar male:female differences, providing strong evidence that sex-specific differences in recombination rates are established at or before the formation of meiotic DSBs. We then asked whether these differences might be linked to variation in the organization of the meiotic axis and/or axis-associated DNA and, indeed, we observed striking male:female differences in synaptonemal complex (SC) length and DNA loop size. Taken together, our observations suggest that sex specific differences in recombination in humans may derive from chromatin differences established prior to the onset of the recombination pathway.
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Gruhn
authors.affiliation: Preimplantation Genetic Diagnosis Unit, Iviomics, Paterna, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hunt
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Terry
authors.initials: T
authors.lastname: Hassold
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000782:Aneuploidy; D003584:Cytological Techniques; D053903:DNA Breaks, Double-Stranded; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis / Q000502:physiology*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000502:physiology*; D012727:Sex Characteristics; D013573:Synaptonemal Complex / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1