Chronic alterations in ovine maternal corticosteroid levels influence uterine blood flow and placental and fetal growth

Abstract

Previous work from this laboratory demonstrated that the elevation of maternal plasma corticosteroid concentrations during pregnancy is important for the support of fetal development. Reducing ovine maternal plasma cortisol concentrations to nonpregnant levels stimulates homeostatic responses that defend fetal blood volume. The present study was designed to test the hypothesis that chronic decreases or increases in maternal plasma cortisol concentration alter uterine and placental blood flow and morphology. Three groups of pregnant ewes and their fetuses were chronically catheterized and studied: ewes infused with cortisol (1 mg.kg(-1).day(-1); high cortisol), ewes adrenalectomized and underreplaced with cortisol (0.5 mg.kg(-1).day(-1); low cortisol), and control ewes. The normal increment in uterine blood flow between 120 and 130 days was eliminated in the low-cortisol ewes; conversely, uterine blood flow was increased in the high-cortisol group compared with the control group. Fetal arterial blood pressure was increased in the high-cortisol group compared with controls, but there was no increase in fetal arterial pressure from 120 to 130 days of gestation in the low-cortisol group. The fetuses of both low-cortisol and high-cortisol groups had altered placental morphology, with increased proportions of type B placentomes, and overall reduced fetal placental blood flow. The rate of fetal somatic growth was impaired in both low-cortisol and high-cortisol groups compared with the fetuses in the intact group. The results of this study demonstrate that maternal plasma cortisol during pregnancy is an important contributor to the maternal environment supporting optimal conditions for fetal homeostasis and somatic growth.

Cardiac corticosteroid receptors mediate the enlargement of the ovine fetal heart induced by chronic increases in maternal cortisol

“…We did not observe an increase in arterial pressure in response to the moderately elevated cortisol levels indicating that the fetal hearts in this study were not subjected to chronically increased systolic load, a possible trigger to myocyte hypertrophy seen in some other studies. Although in the present study blood pressure was only measured at 10 days of cortisol infusion, in our previous study (Jensen et al 2005) fetal arterial blood pressure was not elevated at either 5 or 10 days of maternal cortisol infusion. The doses of cortisol administered in our study resulted in relatively small increases in fetal cortisol, well below those that have been shown to increase fetal blood pressure in other studies (Wood et al 1987, Tangalakis et al 1992, Unno et al 1999.…”

“…The cortisol dose and the duration of cortisol infusion (10 days) were determined based on a previous study in this laboratory (Jensen et al 2005) showing that infusion at this rate and duration produces levels similar to mild maternal stressors and results in enlargement of the fetal heart.…”

“…Although reductions in maternal cortisol prevent the normal increases in maternal plasma volume and uteroplacental blood flow and reduce fetal growth (Jensen et al 2002a(Jensen et al , 2005, increases in maternal cortisol also alter fetal growth. Chronically increased maternal cortisol levels, within the range that occurs with maternal stress, reduce fetal growth rates while increasing heart growth in fetal sheep (Jensen et al 2002b(Jensen et al , 2005.…”

Collateral Uterine Blood Flow in Holstein Cows during the Third Trimester of Pregnancy

“…The observations of Caton et al [ 2 5 ] s u g g e s t t h a t e s t r o n e , e s t r a d i o l a n d progesterone have some effect on the rate of uterine blood flow. Recently, Jensen et al [26] reported that maintenance of increased cortisol concentrations during pregnancy was essential for the normal gestational increase in uterine blood flow in ewes and that even small reductions in maternal cortisol levels resulted in on altered placental structure and slowing of fetal growth. Unfortunately, we found statistically that neither gravid nor nongravid UBF decreased as gestation progressed to parturition.…”

Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation

“…As such, numerous effects beneficial to pregnancy have already been attributed to aldosterone. These include, but are not limited to maternal plasma volume expansion, improved fetal conditions and size, placental growth and lower maternal blood pressure (2)(3)(4)(5)(6)(7)(8). We recently described that vascular endothelial growth factor (VEGF) alone and in combination with angiotensin II, directs augmented aldosterone production in pregnancy (9), suggesting a physiological survival benefit.…”