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Can peri-ovulatory putrescine supplementation improve egg quality in older infertile women?

  • Yong Tao
  • Alina Tartia
  • Maralee Lawson
  • Mary B. Zelinski
  • Wei Wu
  • Jia-Yin Liu
  • Johan Smitz
  • Marie-Claude Léveillé
  • Arthur Leader
  • Hongmei Wang
  • Timothy Ramsay
  • X. Johné LiuEmail author
Commentary Review
  • 108 Downloads

Abstract

The aging-related decline in fertility is an increasingly pressing medical and economic issue in modern society where women are delaying family building. Increasingly sophisticated, costly, and often increasingly invasive, assisted reproductive clinical protocols and laboratory technologies (ART) have helped many older women achieve their reproductive goals. Current ART procedures have not been able to address the fundamental problem of oocyte aging, the increased rate of egg aneuploidy, and the decline of developmental potential of the eggs. Oocyte maturation, which is triggered by luteinizing hormone (LH) in vivo or by injection of human chorionic gonadotropin (hCG) in an in vitro fertilization (IVF) clinic, is the critical stage at which the majority of egg aneuploidies arise and when much of an egg’s developmental potential is established. Our proposed strategy focuses on improving egg quality in older women by restoring a robust oocyte maturation process. We have identified putrescine deficiency as one of the causes of poor egg quality in an aged mouse model. Putrescine is a biogenic polyamine naturally produced in peri-ovulatory ovaries. Peri-ovulatory putrescine supplementation has reduced egg aneuploidy, improved embryo quality, and reduced miscarriage rates in aged mice. In this paper, we review the literature on putrescine, its occurrence and physiology in living organisms, and its unique role in oocyte maturation. Preliminary human data demonstrates that there is a maternal aging-related deficiency in ovarian ornithine decarboxylase (ODC), the enzyme responsible for putrescine production. We argue that peri-ovulatory putrescine supplementation holds great promise as a natural and effective therapy for infertility in women of advanced maternal age, applicable in natural conception and in combination with current ART therapies.

Keywords

Putrescine Ornithine decarboxylase Oocyte maturation Aneuploidy Infertility Aging Embryo development 

Abbreviations

AZ

Antizyme

COC

Cumulus-oocyte complex

dcSAM

Decarboxylased SAM

DFMO

D,L-α-Difluoromethylornithine

GABA

Gamma-aminobutyric acid

GV

Germinal vesicle or oocyte nucleus

hCG

Human chorionic gonadotropin

IVM

Oocyte in vitro maturation

IVF

In vitro fertilization

LH

Luteinizing hormone

ODC

Ornithine decarboxylase

ROS

Reactive oxygen species

PDE3A

Phosphodiesterase 3A

SAM

S-adenosylmethionine

SAM-DC

SAM decarboxylase

SSAT

Spermidine/spermine N1 acetyltransferase

Notes

Funding information

Supported by a research grant from March of Dimes (6-FY13-126) (to XJL), and by the Office of the Director, National Institutes of Health under Award Number P51OD011092 (to ONPRC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yong Tao
    • 1
    • 2
  • Alina Tartia
    • 1
  • Maralee Lawson
    • 3
  • Mary B. Zelinski
    • 3
  • Wei Wu
    • 4
  • Jia-Yin Liu
    • 4
  • Johan Smitz
    • 5
  • Marie-Claude Léveillé
    • 1
    • 6
  • Arthur Leader
    • 1
    • 6
  • Hongmei Wang
    • 7
  • Timothy Ramsay
    • 2
  • X. Johné Liu
    • 2
    • 6
    Email author
  1. 1.Ottawa Fertility CenterOttawaCanada
  2. 2.Ottawa Hospital Research InstituteThe Ottawa Hospital-General CampusOttawaCanada
  3. 3.Oregon National Primate Research CenterBeavertonUSA
  4. 4.Clinical Center of Reproductive Medicine, The First Affiliated HospitalNanjing Medical UniversityNanjingChina
  5. 5.Center for Reproductive Medicine, Academisch ZiekenhuisVrije Universiteit BrusselBrusselsBelgium
  6. 6.Department of Obstetrics and GynecologyUniversity of OttawaOttawaCanada
  7. 7.State Key Laboratory of Stem Cell and Reproductive Biology, Institute of ZoologyChinese Academy of SciencesBeijingChina

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