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Cecilia S Blengini, Gyu Ik Jung, Mansour Aboelenain, and Karen Schindler

In brief

The Aurora protein kinases have critical functions in controlling oocyte meiotic maturation. In this study, we describe an assay for examining their activation state in oocytes and establish the best working doses of three commonly used inhibitors.

Abstract

Several small molecule inhibitors exist for targeting Aurora kinase proteins in somatic cells. From this point of view, we evaluate the specificity of these inhibitors in mouse oocytes, and we demonstrate that MLN 8237 and AZD 1152 are specific for Aurora kinase A and Aurora kinase C, respectively, only when used at low concentrations.

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Leelabati Biswas, Katarzyna Tyc, Warif El Yakoubi, Katie Morgan, Jinchuan Xing, and Karen Schindler

Idiopathic or ‘unexplained’ infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy infants require chromosomally normal (euploid) eggs and sperm. The crux of euploid egg production is error-free meiosis. Pathologic genetic variants dysregulate meiotic processes that occur during prophase I, meiotic resumption, chromosome segregation, and in cell cycle regulation. This dysregulation can result in chromosomally abnormal (aneuploid) eggs. In turn, egg aneuploidy leads to a broad range of clinical infertility phenotypes, including primary ovarian insufficiency and early menopause, egg fertilization failure and embryonic developmental arrest, or recurrent pregnancy loss. Therefore, maternal genetic variants are emerging as infertility biomarkers, which could allow informed reproductive decision-making. Here, we select and deeply examine human genetic variants that likely cause dysregulation of critical meiotic processes in 14 female infertility-associated genes: SYCP3, SYCE1, TRIP13, PSMC3IP, DMC1, MCM8, MCM9, STAG3, PATL2, TUBB8, CEP120, AURKB, AURKC, andWEE2. We discuss the function of each gene in meiosis, explore genotype-phenotype relationships, and delineate the frequencies of infertility-associated variants.