Page 69 - PRECONGRESS COURSE 03

OOCYTE MATURATION ARREST CASES
microtubules DNA
microtubules
DNA
• Patient case reports and series (by 2012, 17 reports, 30 patients)
• M-I arrest cases with a spectrum of spindle and chromosome abnormalities
➾ Identification of intrinsic defects in oocytes without knowledge of specific gene targets
OOCYTE MATURATION ARREST
GENETIC CAUSES
In 2016, mutations in TUBB8 were pinpointed as a common underlying cause of oocyte meiotic arrest
• Families with history of complete oocyte maturation arrests
• Whole-exome sequencing
• Novel mutations and structural deletions in beta tubulin isotype, TUBB8 (oocytes/early embryos, primates only)
• 21/52 patients (40%)
• Phenotypic variability for the different mutations of TUBB8
• Testing of the function of these mutations in vitro (HeLa cells, yeast cells, mouse oocytes, human oocytes)
• May lead to the development of diagnostic tools to screen patients and for evaluation of oocyte dysfunction
• Need to expand such approach to the discovery of other genes that may lead to maturation and fertilization failures
Feng et al., 2016a; Feng et al., 2016b; Chen et al., 2017
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PRECONGRESS COURSE 03 I GENEVA, SWITZERLAND – 2 JULY 2017 69
Heindryckx et al., 2011 Combelles et al., 2003
Combelles et al., unpublished