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

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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.

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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

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Funding

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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Authors and Affiliations

  1. Ottawa Fertility Center, Ottawa, Canada

    Yong Tao, Alina Tartia, Marie-Claude Léveillé & Arthur Leader

  2. Ottawa Hospital Research Institute, The Ottawa Hospital-General Campus, 501 Smyth Road, Box 511, Ottawa, K1H 8L6, Canada

    Yong Tao, Timothy Ramsay & X. Johné Liu

  3. Oregon National Primate Research Center, Beaverton, OR, USA

    Maralee Lawson & Mary B. Zelinski

  4. Clinical Center of Reproductive Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China

    Wei Wu & Jia-Yin Liu

  5. Center for Reproductive Medicine, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels, Belgium

    Johan Smitz

  6. Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Canada

    Marie-Claude Léveillé, Arthur Leader & X. Johné Liu

  7. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Hongmei Wang

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  1. Yong Tao
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Correspondence to X. Johné Liu.

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Tao, Y., Tartia, A., Lawson, M. et al. Can peri-ovulatory putrescine supplementation improve egg quality in older infertile women?. J Assist Reprod Genet 36, 395–402 (2019). https://doi.org/10.1007/s10815-018-1327-x

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