Effects of early- and late-gestational maternal stress and synthetic glucocorticoid on development of the fetal hypothalamus–pituitary–adrenal axis in sheep

Figures & data

Figure 1.  Maternal cortisol response profiles in venous blood samples from pregnant sheep exposed to repeated isolation stress for 3 h twice a week in early gestation [30–100 days gestation (dGA), n = 18]. Data are mean ± SEM; *P < 0.001, 30 dGA vs. 88 dGA; ^# P < 0.001, 30 dGA vs. the following dGA; $ represents all groups, P < 0.001, − 30 min vs. 15 min; Friedman's ANOVA and/or Wilcoxon paired test.

Figure 2.  Integrated maternal cortisol response in pregnant sheep exposed to repeated isolation stress for 3 h twice a week at selected isolation bouts in early [30–100 days gestation (dGA), n = 18] and late (100–120 dGA, n = 7) gestation. Data are mean ± SEM; *P < 0.001 compared to baseline; ^# P < 0.001 compared to 30 dGA; ^§ P < 0.001 compared to later gestational ages; Wilcoxon paired test.

Table I.  Fetal physiological parameters before hypotensive challenge.

	Controls	BM	Early stress	Late stress
112 dGA
FBP (mmHg)	38.6 ± 1.0	37.7 ± 0.8	38.9 ± 0.9
FHR (min^− 1)	181.8 ± 2.9	186.0 ± 2.7	179.2 ± 4.3
pH	7.35 ± 0.01	7.35 ± 0.01	7.33 ± 0.02
pCO2 (mmHg)	41.9 ± 3.1	43.7 ± 2.8	41.1 ± 3.7
pO2 (mmHg)	27.2 ± 1.1	25.5 ± 1.8	24.6 ± 2.0
O2 sat. (%)	74.2 ± 4.4	75.4 ± 4.6	77.7 ± 5.0
129 dGA
FBP (mmHg)	43.3 ± 0.8*	42.9 ± 1.8*	43.8 ± 1.6*	40.7 ± 1.1
FHR (min^− 1)	161.5 ± 5.1*	162.8 ± 2.7*	162.8 ± 4.0*	175.7 ± 6.4
pH	7.35 ± 0.01	7.37 ± 0.02	7.37 ± 0.02	7.35 ± 0.02
pCO2 (mmHg)	40.7 ± 3.1	44.7 ± 1.3	39.6 ± 3.3	43.2 ± 2.0
pO2 (mmHg)	28.3 ± 1.8	26.0 ± 2.1	25.4 ± 2.0	27.3 ± 0.2
O2 sat. (%)	76.6 ± 2.3	79.8 ± 2.7	80.0 ± 4.6	81.7 ± 7.1

Notes: Fetal physiological parameters in controls (n = 7), early (30–100 dGA, n = 7), and late (100–120 dGA, n = 7) isolation-stressed and BM-treated ewes (n = 7) before a hypotensive challenge induced by fetal infusion of SNP; FBP, fetal arterial blood pressure; FHR, fetal heart rate. Data are mean ± SEM. *P < 0.05 compared to 112 dGA by Wilcoxon paired test.

Figure 3.  Fetal carotid arterial blood cortisol responses to hypotensive challenge induced by fetal jugular vein infusion of SNP at 112 and 129 days gestation (dGA) in controls (n = 7), early (30–100 dGA, n = 7), and late (100–120 dGA, n = 7) isolation stressed ewes, and following maternal BM administration at 106/107 and 112/113 dGA (n = 7). Data are mean ± SEM; *P < 0.05 compared to controls; ^§ P < 0.05 compared to baseline; ^# P < 0.05 compared to control, late stress, or BM groups, 15 min after the end of SNP infusion; Kruskal–Wallis ANOVA, Mann–Whitney U-test, and/or Wilcoxon paired test.

Table II.  Fetal physiological parameters during hypotensive challenge.

	Controls	BM	Early stress	Late stress
112 dGA
Base FBP (mmHg)	38.6 ± 1.0	37.7 ± 0.8	38.9 ± 0.9
Min FBP (mmHg)	25.3 ± 1.0*	20.8 ± 1.8*	19.6 ± 1.8^*,§
Base FHR (min^− 1)	181.8 ± 2.9	186.0 ± 2.7	179.2 ± 4.3
Peak FHR (min^− 1)	204.8 ± 4.2*	217.4 ± 11.6*	251.1 ± 5.2^*,§
129 dGA
Base FBP (mmHg)	43.3 ± 0.8	42.9 ± 1.8	43.9 ± 1.6	40.7 ± 1.1
Min FBP (mmHg)	27.2 ± 1.0*	23.9 ± 1.3*	20.6 ± 1.6^*,§	22.4 ± 1.1^*,§
Base FHR (min^− 1)	161.5 ± 5.1	162.8 ± 2.7	162.8 ± 4.0	175.7 ± 6.4
Peak FHR (min^− 1)	193.9 ± 8.9*	199.1 ± 9.0*	221.8 ± 7.2^*,§	227.4 ± 4.2^*,§

Notes: Baseline fetal arterial blood pressure (Base FBP) and baseline fetal heart rate (Base FHR) before, and minimum FBP (Min FBP) and peak fetal heart rate (Peak FHR) at the end of a hypotensive challenge induced by fetal infusion of SNP in controls (n = 7), or in ewes exposed to isolation stress early [30–100 days gestation (dGA), n = 7] and late (100–120 dGA, n = 7), and in ewes after a first course of prenatal BM treatment applied at 106/107 dGA (n = 7). Data are mean ± SEM. *P < 0.05 compared to baseline by Wilcoxon paired test, ^§ P < 0.05 compared to controls by Mann–Whitney U-test.

Figure 4.  Integrated fetal carotid arterial blood cortisol responses to hypotensive challenge at 129 days gestation (dGA) induced by fetal jugular vein infusion of SNP in controls (n = 7), early (30–100 dGA, n = 7), and late (100–120 dGA, n = 7) isolation stressed ewes, and following BM administration at 106/107 and 112/113 dGA (n = 7). Data are mean ± SEM; *P < 0.05 compared to controls; ^§ P < 0.05 compared to late stress or BM; Kruskal–Wallis ANOVA and Mann–Whitney U-test.