A model that explains the varying frequency of aneuploid children with maternal age (J-shaped curve) as well as aneuploidy of paternal origin.
A compromised microcirculation could account for aneuploidy incidence in women of any reproductive age, the frequency varying with the probability of events leading to reduced development and/or function of the critical perifollicular capillary bed. This would explain the J-shaped curve of changing frequency of Down syndrome children with maternal age (Erickson, 1978). The seminiferous tubule of the testis, like the follicle, has no internal circulation, so small localized regions of reduced circulation could occur and result in aneuploidy. From all that we know about the deficiency of regional microcirculation in tumors (see Hall, 1978), it is reasonable to speculate that reduced pH could be responsible for some of the aneuploidy that is seen in practically all advanced tumors. As a first step in testing the model proposed here, we are beginning studies with mouse oocytes, on the assumption that ovarian conditions are responsible for the maternal age effect rather than uterine conditions (reduced rejection of trisomic fetuses). Should our model for aneuploidy induction in both germ and somatic cells prove to be correct, the molecular mechanism(s) would still have to be ascertained.
Gaulden
M E
ME
Radiology Department, University of Texas Southwestern Medical Center, Dallas 75235.
D000782:Aneuploidy; D002648:Child; D005220:Fathers; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008423:Maternal Age; D008833:Microcirculation; D008957:Models, Genetic; D010053:Ovary / Q000098:blood supply / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology