Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00558062" target="_blank" >RIV/68378050:_____/22:00558062 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00335-022-09954-z" target="_blank" >https://link.springer.com/article/10.1007/s00335-022-09954-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00335-022-09954-z" target="_blank" >10.1007/s00335-022-09954-z</a>
Alternative languages
Result language
angličtina
Original language name
Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Mammalian Genome
ISSN
0938-8990
e-ISSN
1432-1777
Volume of the periodical
33
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
590-605
UT code for WoS article
000799551200001
EID of the result in the Scopus database
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