Chromosome errors in human eggs shape natural fertility over reproductive lifespan

• Published in: Science (American Association for the Advancement of Science) Vol. 365; no. 6460; pp. 1466 - 1469
• Main Authors: Gruhn, Jennifer R., Zielinska, Agata P., Shukla, Vallari, Blanshard, Robert, Capalbo, Antonio, Cimadomo, Danilo, Nikiforov, Dmitry, Chan, Andrew Chi-Ho, Newnham, Louise J., Vogel, Ivan, Scarica, Catello, Krapchev, Marta, Taylor, Deborah, Kristensen, Stine Gry, Cheng, Junping, Ernst, Erik, Bjørn, Anne-Mette Bay, Colmorn, Lotte Berdiin, Blayney, Martyn, Elder, Kay, Liss, Joanna, Hartshorne, Geraldine, Groendahl, Marie Louise, Rienzi, Laura, Ubaldi, Filippo, McCoy, Rajiv, Lukaszuk, Krzysztof, Andersen, Claus Yding, Schuh, Melina, Hoffmann, Eva R.
• Format: Journal Article
• Language: English
• Published: 27-09-2019
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aav7321

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.