Assisted Reproductive Technology, Epigenetics, and Long-Term Health: A Developmental Time Bomb Still Ticking

Kristen S Grace; Kevin D Sinclair

doi:10.1055/s-0029-1237429

Seminars in Reproductive Medicine, Table of Contents

Semin Reprod Med 2009; 27(5): 409-416
DOI: 10.1055/s-0029-1237429

Assisted Reproductive Technology, Epigenetics, and Long-Term Health: A Developmental Time Bomb Still Ticking

Kristen S. Grace¹ , Kevin D. Sinclair²

¹Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
²Center for Reproduction and Early Life, School of Biosciences, University of Nottingham, Sutton Bonington, Leicestershire, United Kingdom

Abstract

ABSTRACT

Live birthrates following assisted reproduction account for 1 to 3% of pregnancies in developed countries, and these figures seem set to rise. Concerns regarding the safe use of assisted reproductive technology (ART) for the treatment of infertility have been voiced for several years, yet, to date, the vast majority of children conceived using these techniques are apparently normal. Controversy surrounding reports of epigenetic alterations to genomic imprinting following human ART in recent years has fueled the ongoing debate. In contrast, both the incidence and severity of such anomalies are more apparent following ART in comparative animal species. The reasons for this are not known. By and large, the confounding effects of infertility and advanced maternal age do not apply to animal studies, which report better pregnancy rates following embryo transfer. Perhaps the incidence of imprinting disorders is increased when procedures such as ovarian stimulation, in vitro maturation, or both are used in conjunction with extended periods of embryo culture; this frequently occurs in animal but rarely in human ART. The focus of attention on imprinting, however, may have served to distract the scientific community from more subtle epigenetic modifications to nonimprinted loci in gametes and the preimplantation embryo, with health-related consequences that do not manifest until adulthood. Accumulating evidence from animal studies indicates that such effects, not yet apparent in human subjects, exist; and this may ultimately transpire to be the true developmental legacy of human ART. This article discusses these issues in the context of epigenetic and developmental abnormalities following ART in animals.

KEYWORDS

Artificial reproductive techniques - imprinting - embryogenesis - in vitro culture - prenatal development

Full Text

References

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Kevin D SinclairPh.D.

School of Biosciences, University of Nottingham, Sutton Bonington Campus

Leicestershire LE12 5RD, United Kingdom

Email: kevin.Sinclair@nottingham.ac.uk