Influence of follicular fluid meiosis-activating sterol on aneuploidy rate and precocious chromatid segregation in aged mouse oocytes.

Abstract

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 microM 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 SMC1beta 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 alpha-minimum essential medium (alpha-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 Smc1beta 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 Smc1beta 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.

• Authors: S Cukurcam, I Betzendahl, G Michel, E Vogt, C Hegele-Hartung, B Lindenthal, U Eichenlaub-Ritter
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 22 Issue 3 Pg. 815-28 (Mar 2007) ISSN: 0268-1161 [Print] England
• PMID: 17114196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Cholestenes
• Mad2 Proteins
• Mad2l1 protein, mouse
• Organic Chemicals
• Smc1l2 protein, mouse
• alpha minimal essential medium
• Hypoxanthine
• 4,4-dimethylcholesta-8,14,24-trienol

Topics

• Aging
• Animals
• Cell Cycle Proteins (biosynthesis)
• Cellular Senescence
• Cholestenes (pharmacology)
• Chromatids (physiology)
• Chromosome Segregation (drug effects, physiology)
• Female
• Hypoxanthine (pharmacology)
• Mad2 Proteins
• Meiosis (drug effects)
• Mice
• Mice, Inbred CBA
• Oocytes (physiology)
• Organic Chemicals
• Polyploidy