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Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy
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SYSNO ASEP 0558062 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy Author(s) Gašić, Srdjan (UMG-J)
Mihola, Ondřej (UMG-J) RID, ORCID
Trachtulec, Zdeněk (UMG-J) RID, ORCIDNumber of authors 3 Source Title Mammalian Genome. - : Springer - ISSN 0938-8990
Roč. 33, č. 4 (2022), s. 590-605Number of pages 16 s. Publication form Online - E Language eng - English Country US - United States Keywords trisomic pregnancy ; mice lacking ; mouse ; recombination ; age ; meiosis ; protein ; fetal ; gene ; progression Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA16-06548S GA ČR - Czech Science Foundation (CSF) GA19-06272S GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure CESNET II - 90042 - CESNET - zájmové sdružení právnických osob Method of publishing Limited access Institutional support UMG-J - RVO:68378050 UT WOS 000799551200001 DOI 10.1007/s00335-022-09954-z Annotation Aneuploidy (abnormal chromosome number) accompanies reduced ovarian function in humans and mice, but the reasons behind this concomitance remain underexplored. Some variants in the human gene encoding histone-3-lysine-4,36-trimethyltransferase PRDM9 are associated with aneuploidy, and other variants with ovarian function reduced by premature ovarian failure (POF), but no link between POF and aneuploidy has been revealed. SHR/OlaIpcv rat females lacking PRDM9 manifest POF-a reduced follicle number, litter size, and reproductive age. Here, we explored this model to test how POF relates to oocyte euploidy. The mutant rat females displayed increased oocyte aneuploidy and embryonic death of their offspring compared to controls. Because rat PRDM9 positions meiotic DNA breaks, we investigated the repair of these breaks. Fertile control rodents carry pachytene oocytes with synapsed homologous chromosomes and repaired breaks, while sterile Prdm9-deficient mice carry pachytene-like oocytes with many persisting breaks and asynapsed chromosomes. However, most PRDM9-lacking rat oocytes displayed a few persisting breaks and non-homologous synapsis (NHS). HORMAD2 protein serves as a barrier to sister-chromatid repair and a signal for the synapsis and DNA repair checkpoints. NHS but not asynapsis was associated with HORMAD2 levels similar to the levels on rat pachytene chromosomes with homologous synapsis. NHS was accompanied by crossing-over decreased below the minimum that is essential for euploidy. We argue that the increased mutant rat aneuploidy is due to NHS, which allows some oocytes to pass meiotic checkpoints without one crossing-over per chromosomal pair, leading to segregation errors, and thereby NHS links POF to aneuploidy. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2023 Electronic address https://link.springer.com/article/10.1007/s00335-022-09954-z
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