Human oocytes harboring damaged DNA can complete meiosis I
Mouse oocytes with damaged DNA arrest in meiosis I. Strikingly, DNA damage in human oocytes does not prevent progression to metaphase II and therefore persists in morphologically normal human eggs.
Volume 113, Issue 5, Pages 1080–1089.e2
Gaudeline Rémillard-Labrosse, Ph.D., Nicola L. Dean, Ph.D., Adélaïde Allais, M.Sc., Aleksandar I. Mihajlović, Ph.D., Shao Guang Jin, M.D., Ph.D., Weon-Young Son, Ph.D., Jin-Tae Chung, M.Sc., Melissa Pansera, M.Sc., Sara Henderson, M.Sc., Alina Mahfoudh, M.Sc., Naama Steiner, M.D., Kristy Agapitou, B.Sc., Petros Marangos, Ph.D., William Buckett, M.D., Jacob Ligeti-Ruiter, M.D., Greg FitzHarris, Ph.D.
To determine whether human oocytes possess a checkpoint to prevent completion of meiosis I when DNA is damaged.
DNA damage is considered a major threat to the establishment of healthy eggs and embryos. Recent studies found that mouse oocytes with damaged DNA can resume meiosis and undergo germinal vesicle breakdown (GVBD), but then arrest in metaphase of meiosis I in a process involving spindle assembly checkpoint (SAC) signaling. Such a mechanism could help prevent the generation of metaphase II (MII) eggs with damaged DNA. Here, we compared the impact of DNA-damaging agents with nondamaged control samples in mouse and human oocytes.
University-affiliated clinic and research center.
Patients undergoing ICSI cycles donated GV-stage oocytes after informed consent; 149 human oocytes were collected over 2 years (from 50 patients aged 27–44 years).
Mice and human oocytes were treated with DNA-damaging drugs.
Main Outcome Measure(s)
Oocytes were monitored to evaluate GVBD and polar body extrusion (PBE), in addition to DNA damage assessment with the use of γH2AX antibodies and confocal microscopy.
Whereas DNA damage in mouse oocytes delays or prevents oocyte maturation, most human oocytes harboring experimentally induced DNA damage progress through meiosis I and subsequently form an MII egg, revealing the absence of a DNA damage–induced SAC response. Analysis of the resulting MII eggs revealed damaged DNA and chaotic spindle apparatus, despite the oocyte appearing morphologically normal.
Our data indicate that experimentally induced DNA damage does not prevent PBE in human oocytes and can persist in morphologically normal looking MII eggs.