RESUMO
Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocyte elimination in meiotic mutants require RNF212. RNF212 sensitizes oocytes to DSB-induced apoptosis within a narrow window as chromosomes desynapse and cells transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality-control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.
Assuntos
Dano ao DNA/genética , Reparo do DNA/genética , Oócitos/fisiologia , Animais , Proteínas de Ciclo Celular/genética , Pareamento Cromossômico/genética , Quebras de DNA de Cadeia Dupla , Feminino , Ligases/genética , Masculino , Meiose/genética , Camundongos , Controle de Qualidade , Recombinação Genética/genéticaRESUMO
Pregnant women and individuals with sickle cell trait (SCT) and underlying comorbidities are both independently more vulnerable to severe illness from coronavirus disease 2019 (COVID-19) compared to nonpregnant women and those without SCT. However, our understanding of the specific factors influencing susceptibility to COVID-19 infection among pregnant women with SCT is currently constrained by limited available data. This study aims to determine the risk and protective factors that influence the likelihood of COVID-19 infection in this population. A retrospective analysis was done among 151 women with SCT in the reproductive age group. Multivariable analysis was performed to determine the various factors affecting COVID-19 infection among pregnant women with SCT. The study found that COVID-19-vaccinated pregnant women with SCT had a 90% lower risk of contracting COVID-19 and were 9 times more likely to have a COVID-19 infection if they had a history of pulmonary conditions such as asthma or chronic obstructive pulmonary disease. The present study further emphasizes the importance of the COVID-19 vaccine in preventing infection and safeguarding the health of pregnant women with SCT, particularly those with underlying comorbidities.