Comparison of cattle derived from in vitro fertilization, multiple ovulation embryo transfer, and artificial insemination for milk production and fertility traits

Manipulation or non-physiological embryo culture environments can lead to defective fetal programming in livestock. Our demonstration of reduced fetal methylation and expression of ovine IGF2R suggests pre-implantation embryo procedures may be vulnerable to epigenetic alterations in imprinted genes. This highlights the potential benefits of epigenetic diagnostic screening in developing embryo procedures. Show more

In vitro systems for oocyte maturation, fertilization and embryo culture [in vitro production (IVP)] have the potential for more wide-spread use in creative breeding programs for dairy and beef cattle. However, one negative consequence of both IVP and somatic cell nuclear transfer (SCNT) in cattle and other species is that embryos, fetuses, placentas, and offspring can differ significantly in morphology and developmental competence compared with those from embryos produced in vivo. Fetuses and placentas derived from IVP and SCNT embryos may fall within the normal range of development, may have obvious abnormalities such as increased fetal and placental weights, or may have subtle abnormalities such as aberrant development of fetal skeletal muscle, placental blood vessels, and altered metabolism. Failures in physiologic and/or genetic mechanisms essential for proper fetal growth and survival outside of the uterus contribute significantly to pregnancy and neonatal losses. Oversized fetuses are at increased risk of death during parturition and the adverse consequences of severe dystocia may compromise the dam. Collectively, these abnormalities have been referred to as 'large offspring syndrome' or 'large calf syndrome'. Abnormal phenotypes resulting from IVP and SCNT embryos are stochastic in occurrence and they have not been consistently linked to aberrant expression of single genes or specific pathophysiology. Thus, reliable methods of early diagnosis of the condition are not yet available. The objective of this paper is to examine abnormal development of fetuses and placentas resulting from embryos produced using in vitro systems. The term 'abnormal offspring syndrome (AOS)' is introduced and a classification system of developmental outcomes is proposed to facilitate research efforts on the mechanisms of the various abnormal phenotypes. We also discuss potential genetic and physiologic mechanisms that may contribute to abnormal phenotypes following transfer of IVP and SCNT embryos. Show more

Epidemiology is the branch of science that investigates the causes and distribution of disease in populations in order to provide preventative measures and promote human health. The fields of genetic and environmental epidemiology primarily seek to identify genetic and environmental risk factors for disease, respectively. Epigenetics is emerging as an important piece of molecular data to include in these studies because it can provide mechanistic insights into genetic and environmental risk factors for disease, identify potential intervention targets, provide biomarkers of exposure, illuminate gene-environment interactions and help localize disease-relevant genomic regions. Here, we describe the importance of including epigenetics in genetic and environmental epidemiology studies, provide a conceptual framework when considering epigenetic data in population-based studies and touch upon the many challenges that lie ahead. Show more