Preimplantation Stress and Development

Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, California, 94115.
Birth Defects Research Part C Embryo Today Reviews (Impact Factor: 3.87). 12/2012; 96(4):299-314. DOI: 10.1002/bdrc.21022
Source: PubMed

ABSTRACT The developmental origins of health and disease hypothesis holds that inappropriate environmental cues in utero, a period marked by tremendous developmental sensitivity, facilitate cellular reprogramming to ultimately predispose disease in adulthood. In this review, we analyze if stress during early stages of development can affect future health. This has wide clinical importance, given that 5 million children have been conceived with assisted reproductive technologies (ART). Because the primary outcome of assisted reproduction procedures is delivery at term of a live, healthy baby, the postnatal effects occurring outside ofthe neonatal period are often overlooked. To this end, the long-term outcome of ART is appropriately the most relevant concern of the field today. Evidence of adverse consequences is controversial. The majority of studies have concluded no obvious problems in IVF-conceived children, although a number of isolated cases of imprinted diseases, cancers, or malformations have been reported. Given that animal studies suggest alteration of metabolic pathways following preimplantation stress, it will be of great importance to follow-up ART individuals as they enter later stages of adult life. Birth Defects Research (Part C) 96:299-314, 2012. © 2013 Wiley Periodicals, Inc.

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    ABSTRACT: background: The number of children conceived using assisted reproductive technologies (ART) has reached .5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complica- tions, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions pre- disposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed. methods: Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplas- mic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports. results: ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accel- erated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures. conclusions: ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evi- dence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because growth kinetics in early life are particularly relevant to adult metabolic physiology, we advise more rigorous assessment of fetal growth and placental function in human ART pregnancies, as well as continued follow-up of ART offspring throughout post-natal life. Finally, strategies to min-imize embryo manipulations should be adopted whenever possible.
    Human Reproduction Update 06/2014; 16(21). DOI:10.1093/humupd/dmu032
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    ABSTRACT: Iindex of published papers on thermology or temperature measurement Voluime 4: 2011 to 2013
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    ABSTRACT: The Developmental Origins of Health and Disease hypothesis holds that alterations to homeostasis during critical periods of development can predispose individuals to adult-onset chronic diseases like diabetes and metabolic syndrome. It remains controversial whether preimplantation embryo manipulation, clinically used to treat patients with infertility, disturbs homeostasis and affects long-term growth and metabolism. To address this controversy, we have assessed the effects of in vitro fertilization (IVF) on postnatal physiology in mice. We demonstrate that IVF and embryo culture, even under conditions considered optimal for mouse embryo culture, alter postnatal growth trajectory, fat accumulation and glucose metabolism in adult mice. Unbiased metabolic profiling in serum and microarray analysis of pancreatic islets and insulin sensitive tissues (liver, skeletal muscle and adipose tissue) revealed broad changes in metabolic homeostasis, characterized by systemic oxidative stress and mitochondrial dysfunction. Adopting a candidate approach, we identify thioredoxin-interacting protein (TXNIP)-a key molecule involved in integrating cellular nutritional and oxidative states with metabolic response-as a marker for preimplantation stress and demonstrate tissue-specific epigenetic and transcriptional TXNIP misregulation in selected adult tissues. Importantly, dysregulation of TXNIP expression was associated with enrichment for H4 acetylation at the Txnip promoter that persisted from the blastocyst stage through adulthood in adipose tissue. Our data supports the vulnerability of preimplantation embryos to environmental disturbance, and demonstrates that conception by IVF can reprogram metabolic homeostasis through metabolic, transcriptional, and epigenetic mechanisms with lasting effects for adult growth and fitness. This study has wide clinical relevance and underscores the importance of continued follow-up of IVF-conceived offspring.
    Endocrinology 03/2014; 155(5):en20132081. DOI:10.1210/en.2013-2081


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Jul 24, 2014