Key pointsr Maternal hypoxia is a common perturbation that may impair fetal development and programme sex specific disease outcomes in offspring.r There is growing interest in the role of the placenta in mediating the effects of maternal hypoxia on fetal development, particularly in late gestation during maximal fetal growth.r Multiple mechanisms have been proposed to play a role in hypoxia induced impairment of placental development. Here we investigated the role of glucocorticoids and glucose regulation.r This study shows that fetal sex determines placental adaptations to maternal hypoxia: while maternal hypoxia increased maternal glucose and corticosterone levels in both sexes, placental adaptations to impaired maternal physiology were more evident in female fetuses, in which factors responsible for the regulation of glucocorticoids and nutrient transport were most severely affected by maternal hypoxia.Abstract Maternal hypoxia is a common perturbation that can disrupt placental and thus fetal development, contributing to neonatal impairments. Recently, evidence has suggested that physiological outcomes are dependent upon the sex of the fetus, with males more susceptible to hypoxic insults than females. This study investigated the effects of maternal hypoxia during midto late gestation on fetal growth and placental development and determined if responses were sex specific. CD1 mice were housed under 21% or 12% oxygen from embryonic day (E) 14.5 until tissue collection at E18.5. Fetuses and placentas were weighed before collection for gene and protein expression and morphological analysis. Hypoxia reduced fetal weight in both sexes at E18.5 by 7% but did not affect placental weight. Hypoxia reduced placental mRNA levels of the mineralocorticoid and glucocorticoid receptors and reduced the gene and protein expression of the glucocorticoid metabolizing enzyme HSD11B2. However, placentas of female fetuses responded differently to maternal hypoxia than did placentas of male fetuses. Notably, morphology was significantly altered in placentas from hypoxic female fetuses, with a reduction in placental labyrinth blood spaces. In addition mRNA expression of Glut1, Igf2 and Igf1r were reduced in placentas of female fetuses only. In summary, maternal hypoxia altered placental formation in a sex specific manner through mechanisms involving placental vascular development, growth factor and nutrient transporter expression and placental glucocorticoid signalling. This study provides insight into how sex differences in offspring disease development may be due to sex specific placental adaptations to maternal insults. Abbreviations Crh, corticotropin releasing hormone; Crhr1, corticotropin releasing hormone receptor 1; E, embryonic day; Flt1, Fms related tyrosine kinase 1; Glut1, glucose transporter 1; Glut3, glucose transporter 3; Hif1a, hypoxia inducible factor 1 alpha; Hsd11b2, 11 beta hydroxysteroid dehydrogenase type 2; Igf2, insulin like growth factor 2; Igf1r, insulin like growth factor 1 receptor; Igf2r, Insulin like g...

In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.

Prenatal hypoxia is associated with growth restriction and adverse cardiovascular outcomes. Here, we describe renal and cardiovascular outcomes in ageing mouse offspring prenatally exposed to hypoxia (12% O2) from embryonic day 14.5 until birth. At 12 months of age, both male and female offspring exposed to prenatal hypoxia had elevated mean arterial pressure. Glomerular number was reduced by 25% in hypoxia-exposed male, but not female, offspring and this was associated with increased urinary albumin excretion, glomerular hypertrophy and renal fibrosis. Hypoxia-exposed offspring of both sexes were more susceptible to salt-induced cardiac fibrosis, however, renal fibrosis was exacerbated by high salt in males only. In male but not female hypoxia-exposed offspring, renal renin mRNA was increased at weaning. By 12 months, renal renin mRNA expression and concentrations were elevated in both sexes. mRNA expression of At 1a R was also elevated in male hypoxia-exposed offspring at 12 months. These results demonstrate that prenatal hypoxia programs elevated blood pressure and exacerbates salt-induced cardiovascular and renal pathology in a sex specific manner. Given sex differences observed in RAS expression and nephron number, future studies may consider RAS blockade as a therapeutic target in this model.

Key pointsr Maternal hypoxia is a common perturbation that leads to growth restriction and may program vascular dysfunction in adult offspring.r An adverse prenatal environment may render offspring vulnerable to increased cardiovascular risk when challenged with a 'second hit' , such as a high salt diet.r We investigated whether maternal hypoxia impaired vascular function, structure and mechanics in mouse offspring, and also whether this was exacerbated by excess dietary salt intake in postnatal life.r Maternal hypoxia predisposed adult male and female offspring to endothelial dysfunction. r The combination of prenatal hypoxia and high dietary salt intake caused significant stiffening of mesenteric arteries, and also altered structural characteristics of the aorta consistent with vascular stiffening.r The results of the present study suggest that prenatal hypoxia combined with a high salt diet in postnatal life can contribute to vascular dysfunction.Abstract Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O 2 ) or housed under normal conditions (21% O 2 ) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal * These authors contributed equally to this work. hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes.

Vitamin D deficiency is a common risk factor for secondary hyperparathyroidism in nursing home residents despite a climate in which vitamin D nutrition is thought to be ample. However, the daily frusemide dose is a more important predictor of PTH in this population.