Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

A poorly functioning placenta results in impaired exchanges of oxygen, nutrition, wastes and hormones between the mother and her fetus. This can lead to restriction of fetal growth. These growth restricted babies are at increased risk of developing chronic diseases, such as type-2 diabetes, hypertension, and kidney disease, later in life. Animal studies have shown that growth restricted phenotypes are sex-dependent and can be transmitted to subsequent generations through both the paternal and maternal lineages. Altered epigenetic mechanisms, specifically changes in DNA methylation, histone modifications, and non-coding RNAs that regulate expression of genes that are important for fetal development have been shown to be associated with the transmission pattern of growth restricted phenotypes. This review will discuss the subsequent health outcomes in the offspring after growth restriction and the transmission patterns of these diseases. Evidence of altered epigenetic mechanisms in association with fetal growth restriction will also be reviewed.

During pregnancy, systemic and uteroplacental blood flow increase to ensure an adequate blood supply that carries oxygen and nutrients from the mother to the fetus. This results in changes to the function of the maternal cardiovascular system. There is also a pregnancy-induced vasodilation of blood vessels, which is known to have a protective effect on cardiovascular health/function. Additionally, there is evidence that the effects of maternal vascular vasodilation are maintained post-partum, which may reduce the risk of developing high blood pressure in the next pregnancy and reduce cardiovascular risk later in life. At both non-pregnant and pregnant stages, vascular endothelial cells produce a number of vasodilators and vasoconstrictors, which transduce signals to the contractile vascular smooth muscle cells to control the dilation and constriction of blood vessels. These vascular cells are also targets of other vasoactive factors, including Angiotensin II (Ang II) and relaxin. The binding of Ang II to its receptors activates different pathways to regulate the blood vessel vasoconstriction/vasodilation, and relaxin can interact with some of these pathways to induce vasodilation. Based on the available literature, this review outlines the cardiovascular changes that occur in a healthy human pregnancy, supplemented by studies in rodents. A specific focus is placed on vasodilation of blood vessels during pregnancy; the role of endothelial cells and endothelium-derived vasodilators will also be discussed. Additionally, different pathways that are activated by Ang II and relaxin that result in blood vessel dilation will also be reviewed.