Reproductive Technology

Assessment of the Long-Term and Transgenerational Consequences of Perturbing Preimplantation Embryo Development in Mice

Abstract
Perturbations of the development of preimplantation embryos may have long-term consequences for the health of progeny. There are no standardized methods for assessing such risks. The OECD/OCDE 416 Guideline for Testing of Chemicals is a standardized assay for detecting potential toxic effects of chemicals. This study assessed the utility of this guideline for identifying long-term consequences of perturbing preimplantation development. Extended culture of mammalian zygotes commonly results in retarded preimplantation development. Mouse zygotes were cultured in vitro for 96 h until the blastocyst stage (cultured blastocysts) or blastocysts were collected from the day 3.5 uterus (in vivo blastocysts). The resultant blastocysts were transferred to the uterus of psuedopregnant recipients (P-generation). Progeny from both treatments were mated for a further 2 generations (F1- and F2-generations). There was no effect of treatment group on gross fertility across the generations tested. Progeny of the cultured blastocysts had lower body weights to the time of weaning compared to in vivo blastocysts in the P- and F1-generations, but not the F2-generation. At maturity there was no effect of treatment group on body weight, however, thyroid weight was greater in the in vivo blastocyst group in the P-generation, while the brain, pituitary and kidneys were larger in the progeny of the cultured blastocysts in the F1-generation. The OECD/OCDE 416 assessment may have a role as a standardized test for the assessment of biological consequences of perturbing the growth environment of the preimplantation embryo. Embryo culture influenced somatometric parameters of resulting progeny. Some of these were maintained across a generation.

Key words: Embryo • Environment • Assisted Reproductive Technology • In vitro fertilization

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