Abstract
The risk of meiotic segregation errors increases dramatically during a woman’s thirties, a phenomenon known as the maternal age effect. In addition, several lines of evidence indicate that meiotic cohesion deteriorates as oocytes age. One mechanism that may contribute to age-induced loss of cohesion is oxidative damage. In support of this model, we recently reported (Perkins et al. in Proc Natl Acad Sci U S A 113(44):E6823–E6830, 2016) that the knockdown of the reactive oxygen species (ROS)–scavenging enzyme, superoxide dismutase (SOD), during meiotic prophase causes premature loss of arm cohesion and segregation errors in Drosophila oocytes. If age-dependent oxidative damage causes meiotic segregation errors, then the expression of extra SOD1 (cytosolic/nuclear) or SOD2 (mitochondrial) in oocytes may attenuate this effect. To test this hypothesis, we generated flies that contain a UAS-controlled EMPTY, SOD1, or SOD2 cassette and induced expression using a Gal4 driver that turns on during meiotic prophase. We then compared the fidelity of chromosome segregation in aged and non-aged Drosophila oocytes for all three genotypes. As expected, p{EMPTY} oocytes subjected to aging exhibited a significant increase in nondisjunction (NDJ) compared with non-aged oocytes. In contrast, the magnitude of age-dependent NDJ was significantly reduced when expression of extra SOD1 or SOD2 was induced during prophase. Our findings support the hypothesis that a major factor underlying the maternal age effect in humans is age-induced oxidative damage that results in premature loss of meiotic cohesion. Moreover, our work raises the exciting possibility that antioxidant supplementation may provide a preventative strategy to reduce the risk of meiotic segregation errors in older women.
Highlights
We have previously described the use of Drosophila oocytes to model the human maternal age effect and demonstrated that meiotic segregation errors increase significantly when Drosophila oocytes undergo aging (Subramanian and Bickel 2008)
Our earlier experiments monitored age-induced segregation errors in the genetically sensitized smc1Δ/mtrm background (Subramanian and Bickel 2008). These studies demonstrated that aging causes premature loss of cohesion and destabilization of chiasmata which lead to a significant increase in segregation errors in aged versus non-aged oocytes. smc1Δ heterozygotes still have sufficient cohesion to ensure accurate segregation during meiosis under normal conditions
Our results indicate that a modest increase in superoxide dismutase (SOD) protein in Drosophila diplotene oocytes can significantly reduce the incidence of age-dependent segregation errors
Summary
Adrienne T. Perkins and Miranda M. Greig contributed equally to this work.This article is part of a Special Issue on Recent advances in meiosis from DNA replication to chromosome segregation Bedited by Valérie Borde and Francesca Cole, co-edited by Paula Cohen and Scott Keeney^Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00412-019-00702-y) contains supplementary material, which is available to authorized users.Department of Biological Sciences, Dartmouth College, 78 College Street, Hanover, NH 03755, USAPresent address: Intermountain Healthcare Precision Genomics, 600 S. Medical Center Drive, St. George, UT 84770, USA
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