Completion of meiosis in male zebrafish (<Emphasis Type="Italic">Danio rerio</Emphasis>) despite lack of DNA mismatch repair gene <Emphasis Type="Italic">mlh1</Emphasis> |
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Authors: | Marcelo C Leal Harma Feitsma Edwin Cuppen Luiz R França Rüdiger W Schulz |
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Institution: | (1) Science Faculty, Department Biology, Section Endocrinology & Metabolism, Utrecht University, Kruyt Building, Room Z-203, Padualaan 8, NL-3584 CH Utrecht, The Netherlands;(2) Hubrecht Institute for Developmental Biology and Stem Cell Research, Section Functional Genomics and Bioinformatics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands;(3) Laboratory of Cellular Biology, Department of Morphology, Federal University of Minas Gerais, Minas Gerais, Brazil;(4) Institute of Marine Research, P.O. Box 1870, Nordnes, 5817 Bergen, Norway |
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Abstract: | Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the
first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but have aneuploid progeny.
When studying fertility in males in a two-fold more inbred background, we have however observed low numbers of fertilized
eggs (approximately 0.4%). Histological examination of the testis has revealed that all spermatogenic stages prior to spermatids
(spermatogonia, primary spermatocytes, and secondary spermatocytes) are significantly increased in the mutant, whereas the
total weight of spermatids and spermatozoa is highly decreased (1.8 mg in wild-type vs. 0.1 mg in mutants), a result clearly
different from our previous study in which outbred males lack secondary spermatocytes or postmeiotic cells. Thus, a delay
of both meiotic divisions occurs rather than complete arrest during meiosis I in these males. Eggs fertilized with mutant
sperm develop as malformed embryos and are aneuploid making this male phenotype much more similar to that previously described
in the mutant females. Therefore, crossovers are still essential for proper meiosis, but meiotic cell divisions can progress
without it, suggesting that this mutant is a suitable model for studying the cellular mechanisms of completing meiosis without
crossover stabilization.
Marcelo C. Leal and Harma Feitsma contributed equally to this work.
This work was supported by the Brazilian Foundation CAPES, the Cancer Genomics Center (Nationaal Regie Orgaan Genomics), the
European Union-funded FP6 Integrated Project ZF-MODELS, and Utrecht University. |
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Keywords: | DNA repair enzyme Mlh1 Testis Spermatogenesis Male fertility Aneuploidy Zebrafish Danio rerio (Teleostei) |
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