Large fetuses arising from embryos produced in vitro have been shown to exhibit altered organ development in utero, but it is not known whether this persists post natally. Post-natal growth and development was examined in 18 Simmental bulls derived from in vivo frozen-thawed (n = 6), in vitro frozen-thawed (n = 6) or in vitro fresh (n = 6) embryos and reared together post weaning on an ad libitum diet until slaughter at approximately 13 months old. Calves weighing less than 60 kg at birth (n = 11) were classified as normal, and heavier calves (n = 7; all from in vitro embryos) as oversize. Lifetime growth rates and slaughter weights apparently were unaffected by embryo source or birthweight. Mean (+/- s.e.m.) post mortem liver and kidney weights were unaffected by embryo source, but hearts of bulls from in vitro frozen embryos were heavier than those of bulls from in vivo frozen embryos (2.7 +/- 0.04 v 2.3 +/- 0.07 kg, P<0.025). Heart weight per kilogram body weight at slaughter for the 7 perinatally oversize males (4.01 +/- 0.08 g) exceeded that of the other 5 bulls from in vitro embryos (3.60 +/- 0.10 g kg(-1); P<0.04) and the 6 in vivo males (3.56 +/- 0.12 g kg(-1); P<0.02). Overall, one-third of the variation in heart weight at slaughter (r2 = 0.35; P = 0.01) was due to variation in birthweight. This is the first study to demonstrate birthweight-related developmental effects on post-natal organ weight following the transfer of embryos produced in vitro.
Assisted reproductive technologies, as applied to domestic animals, can exert both novel and wide-ranging influences on the development, viability and welfare of offspring. Some of the changes are evident immediately or soon after the time at which a manipulative procedure is carried out, while other changes may not be evident until later in development or, perhaps, may remain undetected throughout an animal's lifetime. The present review explores some of the consequences - in terms of foetal, placental, neonatal and post-natal effects - of exposing embryos of cattle, sheep and other species to in vitro culture per se or, during culture, to physically invasive technologies including gene injection and nuclear transfer. The innate sensitivity of oocytes and recently fertilized eggs to their in vitro environment is illustrated by an examination of the later developmental repercussions resulting from apparently innocuous choices related to in vitro culture medium formulations. In contrast, an inherent resilience and paradoxical readiness to resume development following the traumas of nuclear transfer procedures is also in evidence. The extent to which assisted reproductive technologies will succeed, where relevant, in the domestic animal sector will be influenced by our appreciation of embryo requirements, for both short- and long-term developmental fitness, during their earliest developmental stages. Evidence of species-specific needs is testimony to the challenges ahead. Ultimately, our ability and inclination to resolve the limitations associated with current procedures will probably be greatly enhanced if predictive indicators (genetic, epigenetic or functional markers) of later developmental fitness can be identified.
During the past 12 years, ruminants have provided a focus for some significant advances in mammalian reproductive biotechnologies. Lambs were the first offspring generated after nuclear transfer of fetal or adult cells to enucleated oocytes, and many calves of predetermined gender are today the result of commercialized semen sexing. In 1990, the birth of one calf provided living proof that even 'dead' spermatozoa can be paternal, whereas, more recently, a short-lived gaur calf and viable mouflon lamb represented a novel option for conservation of endangered species. As well as highlights, hazards have emerged, resulting in setbacks or developmental anomalies, such as those associated with the large offspring syndrome which encompasses a range of adverse fetal, placental and post-natal phenomena expressed in ruminants. In this review, the developmental and other consequences of applying manipulative procedures, such as assisted fertilization, semen sexing, cloning and gene transfer, to gametes and embryos from bovine, ovine and caprine species are considered. Although assisted fertilization techniques can overcome mammalian infertility, they also usurp natural gamete selection safeguards, but not always with impunity. In the case of manipulations such as cloning, and to a lesser extent gene transfer, it is evident that nuclear-cytoplasmic interactions and nuclear-mitochondrial DNA interdependences are at least partially damaged or destroyed with a view to reconstruction. Therefore, among surviving zygotes and embryos it is inevitable that the legacy is frequently one of altered genetic, epigenetic or cellular programmes and processes.
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