Cloning and assisted reproductive techniques: Influence on early development and adult phenotype

Abstract

Over the past 40 years, our increased understanding and development of cell and molecular biology has allowed even greater advances in reproductive biology. This is most evident by the development of various aspects of assisted reproductive techniques (ART), generation of transgenic animals, and most recently generation of mammals through somatic cell cloning. To date, cloning from adult somatic cells has been successful in at least 10 mammalian species. Although generating viable cloned mammals from adult cells is technically feasible and the list of successes will only continue to grow with time, prenatal and perinatal mortality is high and live cloned offspring have not been without health problems. The success of many of the proposed applications of the cloning technique obviously depends upon the health and survival of founder animals generated by nuclear transfer. This article summarizes the health consequences of cloning in mice, and discusses possible mechanisms through which these conditions may arise. In addition, we discuss the effects of ART in animal models and in humans. ART also involves some of the same procedures used in cloning, and there are reports that offspring generated by ART sometimes display aberrant phenotypes as well. It is important to point out that although these techniques do sometimes produce abnormalities, the majority of offspring are born apparently normal and survive to adulthood. Additionally, we must emphasize that the effects of ART and cloning observed in animal models do not necessarily indicate that they will occur in humans. In this article, we review studies examining the phenotype of animals generated by cloning and various ART, and discuss clinical implications of these findings.

Serial cloning of pigs by somatic cell nuclear transfer: Restoration of phenotypic normality during serial cloning

“…Placental abnormalities in humans have been associated with adverse effects on the growth and development of the fetus (Sakai et al, 2005). Moreover, it has been shown that, although clones show a high incidence of phenotypic abnormalities such as obesity (Tamashiro et al, 2002) and premature death (Ogonuli et al, 2002) that are thought to arise from placental problems, the progeny of these clones that are generated by natural mating do not have these abnormalities.…”

Suboptimal in vitro culture conditions: an epigenetic origin of long‐term health effects

“…Epigenetic alterations may be corrected during gametogenesis, preventing the inheritance of parental phenotypes (Sakai et al, 2005), however, they can also lead to the transgenerational transmission of specific genetic traits Anway et al, 2005). The probability of particular ART procedures to promote transgenerational effects should be critically evaluated in order to ensure that its application is sufficiently innocuous.…”

Critical Periods for the Development of Obesity

“…The alteration of methylation status in very early embryonic development may also contribute to the obese phenotype observed in embryo transfer and cloning processes. (Sakai et al, 2005). There is evidence that early nutrition has an effect on DNA methylation.…”