000009521 001__ 9521 000009521 005__ 20240410122320.0 000009521 0247_ $$2DOI$$a10.6083/br86b414d 000009521 037__ $$aIR 000009521 245__ $$aInvestigating the formation and rupture of micronucleir and the consequence of cytosolic DNA release in early mammalian embryogenesis 000009521 260__ $$bOregon Health and Science University 000009521 269__ $$a2022 000009521 336__ $$aAbstract 000009521 520__ $$aThe loss and/or gain of whole chromosomes, or aneuploidy, that arises during mammalian preimplantation development can lead to embryo arrest, implantation failure, or spontaneous miscarriage in natural conception and assisted reproduction. Segregation errors can occur meiotically during gametogenesis, or post-zygotically from mitotic cleavage divisions, resulting in the formation of abnormal nuclear structures known as micronuclei that are spatially isolated from the main nucleus. Micronuclei have been detected in embryos from various mammals and are likely a precursor to a dynamic process called cellular fragmentation (CF), or cytoplasmic blebbing. Once formed, a micronucleus may either fuse back with the primary nucleus or persist and undergo unilateral inheritance in subsequent mitotic divisions. Recent studies have shown that the nuclear envelope of micronuclei in somatic cells is quite fragile, and disruptions may cause genetic material to be released into the cytoplasm, triggering the activation of the cyclic GMP-AMP (cGAS)-cyclic GMP-AMP receptor stimulator of interferon genes (STING) DNA-sensing pathway. Using a non-human primate model and a combination of time-lapse imaging, embryo immunostaining, and single-cell DNA sequencing (scDNA-seq), we sought to determine whether the cGAS-STING pathway is functional during preimplantation development and if there are differences in micronuclei fate between young and aged rhesus macaque females. 000009521 540__ $$fCC BY 000009521 542__ $$fIn copyright - joint owners 000009521 650__ $$aAneuploidy$$014738 000009521 650__ $$aMitosis$$022357 000009521 650__ $$aEmbryo Research$$034448 000009521 6531_ $$acellular fragmentation 000009521 6531_ $$amicronuclei 000009521 6531_ $$apreimplantation embryo 000009521 691__ $$aSchool of Medicine$$041369 000009521 692__ $$aDepartment of Molecular and Medical Genetics$$041428 000009521 7001_ $$aBudrewicz, Jacqueline$$uOregon Health and Science University$$041354 000009521 7001_ $$aChavez, Shawn L.$$uOregon Health and Science University$$041354 000009521 711__ $$aResearch Week$$uOregon Health and Science University$$d2022 000009521 8564_ $$9fd766f8e-4e2f-4efa-8ec0-f1998dd2f2e7$$s185349$$uhttps://digitalcollections.ohsu.edu/record/9521/files/Budrewicz-Jacqueline-OHSU-ResearchWeek-2022.pdf 000009521 905__ $$a/rest/prod/br/86/b4/14/br86b414d 000009521 980__ $$aResearch Week