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The effects of epigenetic factor PRDM9 on the fertility of rodent females
Gašić, Srdan ; Trachtulec, Zdeněk (advisor) ; Děd, Lukáš (referee) ; Fulková, Helena (referee)
The Prdm9 gene encodes a histone-3-lysine-4,36-trimethyltransferase that specifies meiotic recombination sites and guides programmed double-strand breaks (DSBs) in mice, rats, and humans. Some vertebrates lost Prdm9 but not fertility throughout evolution, while the removal of Prdm9 caused sterility in some mouse strains, such as C57BL/6 (B6). The reasons for such species-specific fertility differences are unknown. To resolve these different requirements for PRDM9 in fertility, we produced Prdm9 mutants in another mammalian species, Rattus norvegicus, strain SHR/OlaIpcv. The removal of Prdm9 function did not completely abolish fertility in rats (as in B6 mice). Here I demonstrate that the loss of rat PRDM9 delayed female meiosis and caused synapsis and DSB repair defects that lead to a significant oocyte loss. However, unlike Prdm9-deficient B6 mouse oocytes, about 10-15% of pachytene-like mutant rat oocytes synapsed their chromosomes and repaired DSBs to the levels similar to controls. Because of this, female rats lacking PRDM9 maintained some oocytes until adulthood and yielded offspring, while B6 mice lost oocytes around the time of birth. Nevertheless, the adult rat mutant oocytes were exhausted earlier than the control adult rat oocytes. Therefore, PRDM9-lacking female rats suffered from...
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