Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg.

Abstract

The incidence of aneuploidy in eggs from women of advanced reproductive age can exceed 60%, making the mammalian egg a unique model system to study the mechanisms of chromosome segregation errors. Here we applied a novel biophysical chromosome stretching approach to quantify mechanical stiffness of meiotic chromosomes in the mammalian egg and then documented how these properties changed in a mouse model of physiologic reproductive aging. We found significant differences in chromosome micromechanics, and thus in higher order chromosome structure, coincident with advanced reproductive age, a time that is also unequivocally associated with an increase in egg aneuploidy. These findings have important implications for both reproductive and cancer biology where aneuploidy plays a central role in aging related disease states.