Consequences of manipulating gametes and embryos of ruminant species

Abstract

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.

The influence ofin vitrofertilization and embryo culture on the embryo epigenetic constituents and the possible consequences in the bovine model

“…Other problems seen are: a decreased intensity of labor, increases in abortions, congenital malformations, perinatal mortality and on the mother side an increase in hydro allantoides conditions. 52,54 The use of systematic cesarean section reduced perinatal mortality to 2% supporting the hypothesis of the delayed parturition as the possible cause of larger weight for those calves 55 although the syndrome seems to begin during gestation as Farin observed the enlarged phenotype in 7-month-old fetus (compared for gestational age), the complete physiopathology has not been clarified. 6 Such alterations are likely to be associated with placental programming as observed in other species, especially the sheep.…”

Clinical insights: Assisted reproductive technologies

“…Finally, although it is clear that the OPU‐ICSI is in demand and producing commercially viable results, both in terms of number and financial value of the resulting foals, it is not known whether the in vitro manipulations affect the long‐term health or athletic capacity of the resulting offspring, in the way that in vitro embryo production of cattle embryos was once hampered by the ‘large calf syndrome’; the large calf problem was ‘solved’ when it was discovered that the serum commonly included in embryo culture medium was responsible for epigenetic changes (i.e. structural modifications to the DNA that permanently alter gene expression without affecting DNA sequence) that altered foetal development and compromised post‐natal survival . This discovery paralleled other studies demonstrating that the environment to which an embryo is exposed during early (pre‐implantation) development can critically affect its epigenetic programming in a way that can influence health and morbidity throughout post‐natal life.…”