induce similar increases in fetal blood pressure and similar falls in the incidence of fetal breathing movements. The pronounced betamethasone-induced fetal hypertension is associated with an increase in fetal femoral vascular resistance.Antenatal glucocorticoid administration to enhance fetal periventricular haemorrhage and necrotizing enterocolitis lung maturation has been used in obstetric practice over the (Crowley, Chalmers & Keirse, 1990). Thus, the National last 20 years since first reported by Liggins (1969). In Institutes of Health recently advised routine administration addition to the well-known decrease in Respiratory in two to four doses for 48 h of either betamethasome or Distress Syndrome, antenatal administration of either beta-dexamethasone to all pregnant women at risk of premature methasone or dexamethasone, the only two glucocorticoids delivery before 32 weeks of gestation (NIH Consensus used clinically, reduces the incidence of neonatal mortality, Development Conference, 1994).
Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence.
We characterized the detailed hemodynamics of fetal blood pressure, heart rate, common umbilical blood flow, and femoral blood flow responses to partial compression of the umbilical cord and tested the hypothesis that repeated cord compression modulates fetal cardiovascular responses in 10 chronically instrumented fetal sheep at ∼130 days of gestation. In five fetuses ( group I), partial compression of the umbilical cord was induced 12 times, each for 5 min at 15-min intervals. Each cord compression reduced common umbilical blood flow by 50% and produced modest falls in fetal pH (7.33 ± 0 to 7.29 ± 0) and arterial [Formula: see text] (21.1 ± 0.2 to 16.8 ± 0.2 mmHg) and a mild increase in arterial[Formula: see text] (49.9 ± 0.5 to 54.9 ± 0.4 mmHg). Sham experiments were performed in five other fetuses ( group II). Second-by-second analysis of group I fetal cardiovascular data revealed a clear biphasic response to partial cord compression. Phase I (1st min of cord compression) was characterized by a rapid bradycardia and a rapid femoral vasoconstriction (primary response); phase II ( minutes 2–5of cord compression) was characterized by a delayed bradycardia and a return of femoral vascular resistance toward baseline (secondary response). Repeated cord compression abolished the primary, but not the secondary, cardiovascular responses. These results demonstrate that fetal cardiovascular responses to stress may be modified by preexposure to repeated intrauterine challenges.
Glucocorticoid administration to women at risk of preterm delivery to accelerate fetal lung maturation has become standard practice. Antenatal glucocorticoids decrease the incidence of intraventricular haemorrhage as well as accelerating fetal lung maturation. Little is known regarding side effects on fetal cerebral function. Cortisol and synthetic glucocorticoids such as betamethasone increase fetal blood pressure and femoral vascular resistance in sheep. We determined the effects of antenatal glucocorticoid administration on cerebral blood flow (CBF) in fetal sheep. Vehicle (n= 8) or betamethasone (n= 8) was infused over 48 h via the jugular vein of chronically instrumented fetal sheep at 128 days gestation (term 146 days). The betamethasone infusion rate was that previously shown to produce fetal plasma betamethasone concentrations similar to human umbilical vein concentrations during antenatal glucocorticoid therapy. Regional CBF was measured in 10 brain regions, using coloured microspheres, before and 24 and 48 h after onset of treatment, and during hypercapnic challenges performed before and 48 h after onset of betamethasone exposure. Betamethasone exposure decreased CBF in all brain regions measured except the hippocampus after 24 h of infusion (P < 0·05). The CBF decrease was most pronounced in the thalamus and hindbrain (45–50 % decrease) and least pronounced in the cortical regions (35–40 % decrease). It was mediated by an increase in cerebral vascular resistance (CVR, P < 0·05) and led to a decrease in oxygen delivery to subcortical and hindbrain structures of 30–40 %, to 8·6 ± 1·1 ml (100 g)−1 min−1, and 40–45 %, to 11·0 ± 1·6 ml 100 g−1 min−1, respectively (P < 0·05). After 48 h of betamethasone treatment, the reduction in CBF was diminished to about 25–30 %, but was still significant in comparison to vehicle‐treated fetuses in all brain regions except three of the five measured cortical regions (P < 0·05). CVR and oxygen delivery were unchanged in comparison to values at 24 h of treatment. The CBF increase in response to hypercapnia was diminished (P < 0·05). These observations demonstrate for the first time that glucocorticoids exert major vasoconstrictor effects on fetal CBF. This mechanism may protect the fetus against intraventricular haemorrhage both at rest and when the fetus is challenged. Betamethasone exposure decreased the hypercapnia‐induced increase in CBF (P < 0·05) due to decreased cerebral vasodilatation (P < 0.05).
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