Periconceptional Undernutrition in Sheep Accelerates Maturation of the Fetal Hypothalamic-Pituitary-Adrenal Axis in Late Gestation

Abstract

We investigated the effects of moderate maternal periconceptional undernutrition from 60 d before to 30 d after mating on fetal hypothalamic-pituitary-adrenal axis function in late gestation. Ewes were sampled regularly during the period of undernutrition for circulating hormone levels. Vascular catheters were inserted into ewes and their singleton fetuses at 112 d gestation (term, 145 d), and fetal ACTH(1-24) and metyrapone challenge tests were performed at 127 and 128 d. Postmortems were performed at 132 d. Fetuses of undernourished ewes (UN, n = 12) had elevated baseline cortisol concentrations (P < 0.05), compared with fetuses of ad libitum-fed ewes (n = 10). There were no differences between groups in fetal responses to ACTH challenge, but only UN fetuses demonstrated ACTH and 11-deoxycortisol responses to metyrapone (P < 0.05). UN fetuses had increased mRNA levels for proopiomelanocortin and prohormone convertase-1, but not -2, in the pars intermedia of the pituitary gland (P < 0.05). Glucocorticoid receptor mRNA levels were not different between groups in pituitary or hypothalamus. Maternal cortisol and ACTH levels during undernutrition were profoundly suppressed (P < 0.001), rather than elevated, in UN ewes. Furthermore, the normal pregnancy rise in maternal serum progesterone concentrations was delayed in undernourished mothers. These data demonstrate that events around the time of conception have profound effects on fetal hypothalamic-pituitary-adrenal development in late gestation and that factors other than fetal exposure to excess glucocorticoids may be important.

Effects of periconceptional undernutrition on the initiation of parturition in sheep

“…Although the UN group was divided into preterm and term groups for the sake of this analysis, the UN group as a whole delivered early across a wide gestational age range, suggesting that maturation of the fetal HPAA must reach a threshold level to trigger the processes leading to parturition (3). The possible mechanisms underlying this maturation are discussed elsewhere (3,4).…”

Nutritional programming: prenatal nutritional effects on the regulation of growth and metabolism

“…Available evidence suggest that the maternal and/or foetal endocrine systems facilitate such adaptations with the placenta mediating the cross-talk between mother and foetus and acting as a nutrient sensor. A key influence underlying the reprogramming of the foetal hypothalamic-pituitary-adrenal axis, appears to be the exposure of the foetus to excess glucocorticoids derived from maternal circulation (Bertram et al, 2001), or alternatively, a suppression of the maternal HPA axis (Bloomfield et al, 2004). Glucocorticoid hormones are essential mediators of the somatotrophic axis, which regulate nutrient partitioning between the maternal, placental and foetal compartments, and subsequently foetal growth.…”

“…After this period there is a gradual increase in cortisol production. Periconceptual (days -60 to +30), mid (days 28 to 80), and late gestation undernutrition (days 115 to 145) in sheep leads to different maternal plasma cortisol levels which may be related to differences in foetal nutrient demands in the course of gestation (Edwards and McMillen, 2001;Bispham et al, 2003;Bloomfield et al, 2004). In all species studied there is a surge in circulating foetal cortisol concentration before birth.…”

“…In addition to alterations of glucocorticoids, insulin and IGF-1, maternal under-or overnutrition during gestation also was reported to result in changes of other maternal hormone levels such as progesterone, oestrogen, prolactin, thyroid hormones, growth hormone and leptin (Wallace et al, 1997(Wallace et al, , 2003Ashworth et al, 2000;Budge et al, 2000;Thomas et al, 2001;Bispham et al, 2003;Fernandez-Twinn et al, 2003;Bloomfield et al, 2004). Whether glucocorticoids are primarily triggered by foetal nutrient surplus or shortage and act as master regulator orchestrating other endocrine systems is unclear.…”

Avaliação hormonal sérica e estereológica da membrana corioalantóide a termo de éguas: influência no desenvolvimento e nos parâmetros clínicos e metabólicos do potro

“…Em ovelhas, as concentrações maternas de P 4 e lactogênio placentário encontram-se a baixo dos níveis normais em condições adversas, como a desnutrição (BLOOMFIRLD et al, 2004;WALLACE et al, 2004), e podem ser justificadas em parte por uma redução no tamanho da placenta (FOWDEN et al, 2008).…”