RT Journal Article
SR Electronic
T1 NAD<sup>+</sup> repletion rescues female fertility during reproductive ageing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 721985
DO 10.1101/721985
A1 Michael J. Bertoldo
A1 Dave R. Listijono
A1 Wing-Hong Jonathan Ho
A1 Angelique H. Riepsamen
A1 Xing L. Jin
A1 Kaisa Selesniemi
A1 Dale M. Goss
A1 Saabah Mahbub
A1 Jared M. Campbell
A1 Abbas Habibalahi
A1 Wei-Guo Nicholas Loh
A1 Neil A. Youngson
A1 Jayanthi Maniam
A1 Ashley S.A. Wong
A1 Dulama Richani
A1 Catherine Li
A1 Yiqing Zhao
A1 Maria Marinova
A1 Lynn-Jee Kim
A1 Laurin Lau
A1 Rachael M Wu
A1 A. Stefanie Mikolaizak
A1 Toshiyuki Araki
A1 David G. Le Couteur
A1 Nigel Turner
A1 Margaret J. Morris
A1 Kirsty A. Walters
A1 Ewa Goldys
A1 Christopher O’Neill
A1 Robert B. Gilchrist
A1 David A. Sinclair
A1 Hayden A. Homer
A1 Lindsay E. Wu
YR 2019
UL http://biorxiv.org/content/early/2019/08/02/721985.abstract
AB Female infertility is a common and devastating condition with life-long health, emotional and social consequences. There is currently no pharmacological therapy for preserving oocyte quality during aging, which is the strongest risk factor for infertility. This leads to an age dependent decline in natural conception and IVF success rates (1). Here, we show that this is due in part to declining levels of the metabolic cofactor nicotinamide adenine dinucleotide (NAD+), and that restoring NAD+ levels with its metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality and quantity in aged animals, leading to improved fertility. These benefits extend to the developing embryo, where NMN supplementation in embryo culture media following IVF enhances blastocyst formation in older mice. The NAD+ dependent deacylase SIRT2 is sufficient, but not essential, to recapitulate the benefits of in vivo NMN treatment, and transgenic overexpression of SIRT2 maintains oocyte spindle assembly, accurate chromosome segregation, decreased oxidative stress and overall fertility with ageing. Pharmacological elevation of NAD+ may be an effective, non-invasive strategy for restoring and maintaining female fertility during ageing, and for improving the success of IVF.