Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

Intrauterine Growth Retardation in Endothelial Nitric Oxide Synthase-Deficient Mice Is Established from Early Stages of Pregnancy1

“…These effects are related to genetic and infectious factors [36], but also to nutritional challenges [42,44,45] and, mainly, maternal body composition during early pregnancy [46], which, in cows, has been described to be influenced by weight, age, and parity [47]. Coincidentally, incidence of reproductive alterations and fetal programming in NOS3 mice has also been related to parity [9]. Linking early pregnancy, NOS3, and later fetal programming, recent studies have found that placental NOS3 concentration, mainly regulated at midgestation, but also during early and late gestation [48], is influenced by challenges in early gestation [49], equivalent in this current study to the fifth to eighth weeks of pregnancy in humans [50].…”

“…Effects are found to be related to fetal growth retardation and higher mortality at the end of gestation [7,8]. Thus, there is a reduction in the litter size and weight of neonates at delivery (confirmed by [9]), with increased perinatal losses [6]. The publications examining fetal growth [7,8] report that differences in litter size and fetal development were established only at the last days of pregnancy (Day 17 postcoitum [p.c.]).…”

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

“…Maternal undernutrition (58), maternal hypoxia (167,184), and pregnancy at high altitude (174) were also found to reduce maximal responses to KCl in the aorta, carotid, and pulmonary arteries of rat offspring. A maternal low-protein diet in mice (331,332) or rats (406,450), maternal dexamethasone treatment in mice (331), chicken eggs incubated in hypoxic conditions (227,257), offspring of eNOS knockout mice (229), and maternal cocaine exposure (444), however, had no effect on aortic, carotid, mesenteric, femoral, or coronary artery constrictor capacity. In contrast, other studies demonstrated increased constrictor responses to KCl in mesenteric arteries of only male offspring from dams treated with dexamethasone (285), in aorta of offspring from dams exposed to hypoxia (58), in pulmonary arteries of offspring from pregnancies at high altitude (37), and in carotid arteries of offspring of eNOS knockout mice (229).…”

Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model

“…In such later stages of pregnancy, embryo survival and growth are mainly affected by the uterine capacity of the mother (Bennett & Leymaster 1989) and, hence, litter size and weight are highly correlated with maternal body size and weight (Van Engelen et al 1995). Thus, offspring features are enhanced in multiparous Nos3-knockout mothers when compared with primiparous or oligoparous females (Longo et al 2004).…”

“…Studies on the effects from the lack of NOS3 have been afforded by using Nos3-knockout mice, a strain showing elevated blood pressure, decreased heart rate, and premature death in males but not in females; so the model is widely used for cardiovascular research (http:// jaxmice.jax.org/strain/002684.html). The lack of NOS3 in Nos3-knockout mice (Mashimo & Goyal 1999, Gregg 2003 has been found to cause a reduction in the number of offspring and in the weight of the neonates at delivery (Hefler et al 2001, Longo et al 2004, Van der Heijden et al 2005). In the previous studies, these effects have been related to lower fetal growth and higher mortality at the end of gestation (Hefler et al 2001, Van der Heijden et al 2005).…”