Physiological and molecular mechanisms underlying the appearance of the large calf syndrome for in vitro-produced bovine embryos

Mechanisms underlying the appearance of the Large Calf Syndrome were investigated by examination of the effects of embryo production system on physiological and molecular aspects known to influence embryonic, fetal and placental growth. Females were superovulated to obtain in vivo-produced embryos (controls), whereas in vitro-produced (IVP) embryos were derived from in vitro maturation, fertilization and culture procedures. Day-7 blastocysts were transferred to female recipients. Differences between control and IVP groups were examined regarding (a) growth and transcription rates of Day-7 and Day-16 embryos; (b) conceptus development based on pre- and postnatal measurements of concepti and neonates; and (c) placental permeability to D-xylose and association with conceptus development. In vitro production negatively affected development of resulting embryos and concepti. On Day 7, IVP embryos exhibited lower mRNA levels than controls, and on Day 16, IVP concepti were shorter and displayed smaller embryonic discs. Physical traits and transcriptional activity on Day 16 were associated with one another and appeared to be important for growth and development. In vitro-produced pregnancies were characterized by a period of fetal and placental growth retardation during the early weeks of pregnancy (Days 37 to 58). By the end of the first third of gestation, morphological and physiological characteristics were similar between groups, but placentomes in the IVP group were longer and thinner than controls. Toward the end of the second trimester of pregnancy, IVP pregnancies sustained larger concepti and demonstrated an increased transport of D-xylose from the maternal circulation to the fetus and associated fluids. Changes in placental development in the IVP group were associated with the delivery of larger calves and the appearance of aberrant fetal membranes. Suboptimal conditions of in vitro embryo production significantly affected embryo and conceptus development. The early retarded pattern of development appeared to be followed by aberrant placental development, which in turn may have disrupted placental restraint on fetal growth towards the end of pregnancy, culminating with high birth weights. Cause-and-effect relationships between placental physical and functional alterations and accelerated prenatal growth after in vitro embryo manipulation still need to be determined.