Chromosome errors in human eggs shape natural fertility over reproductive life span.
Jennifer R GruhnAgata P ZielinskaVallari ShuklaRobert BlanshardAntonio CapalboDanilo CimadomoDmitry NikiforovAndrew Chi-Ho ChanLouise J NewnhamIvan VogelCatello ScaricaMarta KrapchevDeborah TaylorStine Gry KristensenJunping ChengErik ErnstAnne-Mette Bay BjørnLotte Berdiin ColmornMartyn BlayneyKay ElderJoanna LissGeraldine M HartshorneMarie Louise GrøndahlLaura RienziFilippo UbaldiRajiv C McCoyKrzysztof LukaszukClaus Yding AndersenMelina SchuhEva R HoffmanPublished in: Science (New York, N.Y.) (2020)
Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.