MATERNAL AGE EFFECT: THE ENIGMA OF DOWN SYNDROME AND OTHER TRISOMIC CONDITIONS

Abstract

Aneuploidy is the most frequently observed chromosome abnormality in human liveborn, abortuses, and oocytes. he only etiological factor that has been established is advanced maternal age for the occurrence of trisomies, particularly trisomy 21 which causes Down syndrome. he maternal age effect remains an enigma. ecent molecular data bearing on this question are reviewed as are the hypotheses that have been proposed linking nondisjunction and maternal age. ationale is presented for a compromised microcirculation hypothesis that explains the cause of nondisjunction and why its occurrence changes with maternal age. he hypothesis proposes that aneuploid oocytes arise from a concatenation of events. t begins with hormonal imbalance that causes a less-than-optimal microvasculature to develop around the follicles. he resulting decrease in the size of the perifollicular capillary bed reduces the volume of blood flow through the area, leading to an oxygen deficit and a concomitant increase inside the follicle of carbon dioxide and anaerobic products, such as lactic acid. his in turn causes a decrease in the intracellular pH of the oocyte that diminishes the size of the spindle, with consequent displacement and nondisjunction of a chromosome.

Citation

Gaulden, M. MATERNAL AGE EFFECT: THE ENIGMA OF DOWN SYNDROME AND OTHER TRISOMIC CONDITIONS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/175.

Additional Information

Mutation Research 296(1/2):69-88, 1992

• MATERNAL AGE EFFECT: THE ENIGMA OF DOWN SYNDROME AND OTHER TRISOMIC CONDITIONS