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: 2.63). 12/2012; 96(4):299-314. DOI: 10.1002/bdrc.21022
Source: PubMed


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: The pre-implantation period is a time of reprogramming that may be vulnerable to disruption. This question has wide clinical relevance, since the number of children conceived by in vitro fertilization (IVF) is rising. To examine this question, outbred mice (CF1xB6D2F1) conceived by IVF and cultured using Whitten medium and 20% O2 (IVFWM group, less optimal), or K simplex optimized medium with amino acids and 5% O2 (IVFKAA group, more optimal and similar to conditions used in human IVF), were studied postnatally. We found that flushed blastocysts transferred to recipient mice provided the best control group (FB group), as this accounted for the effects of superovulation, embryo transfer, and litter size. We observed that many physiological parameters were normal. Reassuringly, IVFKAA offspring did not differ significantly from FB offspring. However, male IVFWM mice (but not females) were larger during the first 19 wk of life and exhibited glucose intolerance. Male IVFWM mice also showed enlarged left heart despite normal blood pressure. Expression of candidate imprinted genes (H19, Igf2, and Slc38a4) in multiple adult tissues did not show differences among the groups; only Slc38a4 was down-regulated following IVF (in both culture conditions) in female adipose tissue. These studies demonstrate that adult metabolism is affected by the type of conditions encountered during the pre-implantation stage. Further, the postnatal growth trajectory and glucose homeostasis following ex-vivo manipulation may be sexual dimorphic. Future work on the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular system.
    Preview · Article · Mar 2014 · Biology of Reproduction
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