Hum. Reprod. Advance Access originally published online on November 17, 2006
Human Reproduction 2007 22(3):815-828; doi:10.1093/humrep/del442
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Influence of follicular fluid meiosis-activating sterol on aneuploidy rate and precocious chromatid segregation in aged mouse oocytes
1 Research Laboratories of Schering AG, Berlin and 2 Fakultät für Biologie, Gentechnologie/Biotechnologie, University Bielefeld, Bielefeld, Germany
3 Present address: Charite, Experimental Medicine, Institute of Cell Biology and Neurobiology, 12207 Berlin, Germany
4 To whom correspondence should be addressed at: University of Bielefeld, Faculty of Biology IX, Universitätsstrasse 25, D-33501 Bielefeld, Germany. E-mail: eiri{at}uni-bielefeld.de
BACKGROUND: Follicular fluid meiosis-activating sterol (FF-MAS) protects young oocytes from precocious chromatid separation (predivision). Reduced expression of cohesion and checkpoint proteins and predivision has been hypothesized to occur in age-related aneuploidy in oocytes. METHODS: To know whether FF-MAS also protects aged oocytes from predivision and from age-related non-disjunction, we analysed chromosome constitution in mouse oocytes matured spontaneously with or without 10 µM FF-MAS and in hypoxanthine (HX)-arrested young and aged oocytes induced to resume maturation by FF-MAS. Messenger RNA for checkpoint protein MAD2 and cohesion protein SMC1
was compared between oocytes matured with or without FF-MAS. RESULTS: Aged oocytes possessed many bivalents with single distal chiasma at meiosis I. Predivision was especially high in aged oocytes cultured sub-optimally to metaphase II in 
-minimum essential medium (-MEM). FF-MAS reduced predivision significantly (P < 0.001) but neither reduced non-disjunction nor induced aneuploidy in aged oocytes. Polyploidy was high in FF-MAS-stimulated maturation, in particular in the aged oocytes (P > 0.001). Relative levels of Smc1 mRNA appeared increased by maturation in FF-MAS, and mitochondrial clustering was restored. CONCLUSIONS: Sister chromatids of aged oocytes appear to be highly susceptible to precocious chromatid separation, especially when maturation is under sub-optimal conditions, e.g. in the absence of cumulus and FF-MAS. This may relate to some loss of chromatid cohesion during ageing. FF-MAS protects aged oocytes from predivision during maturation, possibly by supporting Smc1 expression, thus reducing risks of meiotic errors, but it cannot prevent age-related non-disjunction. Aged oocytes appear prone to loss of co-ordination between nuclear maturation and cytokinesis suggesting age-related relaxed cell cycle control.
Key words: oocyte/maturation/meiosis/non-disjunction/age
Submitted on June 16, 2006; resubmitted on August 25, 2006; resubmitted on October 9, 2006; accepted on October 16, 2006.
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