Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans

Abstract

Summary: Cardiovascular diseases are the main cause of mortality and morbidity in Western countries, but the underlying mechanisms are still poorly understood. Genetic polymorphisms, once thought to represent a major determinant of cardiovascular risk, individually and collectively, only explain a tiny fraction of phenotypic variation and disease risk in humans. It is now clear that non-genetic factors, i.e., factors that modify gene activity without changing the DNA sequence and that are sensitive to the environment can cause important alterations of the cardiovascular phenotype in experimental animal models and humans. Here, we will review recent studies demonstrating that distinct pathological events during the perinatal (transient perinatal hypoxemia), late foetal (preeclampsia), and early embryonic (assisted reproductive technologies) periods induce profound alterations of the cardiovascular phenotype in humans and experimental animals. Moreover, we will provide evidence that epigenetic modifi cations are contributing importantly to this problem and are conferring the potential for its transmission to subsequent generations.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

“…There have been reports of increased incidence of placenta accreta, preeclampsia, macrosomia, and large for gestational age as a result of the transfer of frozen-thawed embryos compared to fresh counterparts ( 54 ). Along the same lines, adoption of a freeze-all policy would require additional embryo manipulation that might induce epigenetic changes, and thus further add risk to children born from frozen-thawed embryo transfer cycles ( 55 – 61 ).…”

Intermittent hypoxia in utero damages postnatal growth and cardiovascular function in rats

“…This phase-associated effect would justify further investigation using a modified model. Recent animal and human studies suggest that chronic sustained hypoxia during pregnancy profoundly alters cardiovascular phenotypes (39,41), including growth restriction, left ventricular hypertrophy, and diastolic dysfunction (6,40). Although prenatal CIH shares these features of chronic sustained hypoxia, it is possible that the effects of prenatal CIH differ from that of prenatal sustained hypoxia.…”

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles—A Systematic PRISMA Review and Meta-analysis

“…Furthermore, the segmentation policy after GnRHa trigger in line with previous reports on health outcomes of children born as a result of cryopreserved thawed embryos is likely to increase the incidence of macrosomia and large for gestational age (30–32), the risk of placenta accreta (33, 34), and the risk of preeclampsia (35). Moreover, this additional elective manipulation of gametes which could induce epigenetic changes might add further to the risk of cardiovascular disorders that have already been reported to be associated with ART (36, 37). Finally, a comprehensive evaluation of elective segmentation taking into account cost-effectiveness, patient-centeredness, and time to live birth has yet to be carried out.…”