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|Title:||Placental restriction alters the functional development of the pituitary-adrenal axis in the sheep fetus during late gestation|
|Citation:||Pediatric Research, 1996; 40(6):861-866|
|Publisher:||WILLIAMS & WILKINS|
|Ian D Phillips, Giuseppe Simonetta, Julie A Owens, Jeffrey S Robinson, Iain J Clarke and I Caroline McMillen|
|Abstract:||We have experimentally restricted placental growth in the sheep to investigate the impact of reduced substrate delivery on fetal pituitary proopiomelanocortin (POMC) mRNA levels and on circulating ACTH 1-39, immunoreactive ACTH, and cortisol concentrations during late gestation. Endometrial caruncles were removed in nine ewes before mating to reduce the number of placentomes formed [placental restriction group (PR)]. Fetal arterial Po2 and O2 saturation were reduced in the PR group (2.0± 0.1 kPa and 42.8 ± 1.1%, n = 9) when compared with control fetuses (3.1 ± 0.1 kPa and 66.4 ± 0.9%, n = 10). The ratio of anterior pituitary POMC mRNA:18 S ribosomal RNA was also lower (p < 0.05) in the PR group (0.49 ± 0.05) when compared with the control group (0.80 ± 0.12) after 140 d of gestation. In contrast, plasma concentrations of ACTH 1-39 and immunoreactive ACTH were similar in the PR and control groups throughout late gestation. Plasma ACTH 1-39 concentrations increased (p < 0.006) between 128 and 134 d of gestation, in both the PR (122-128 d: 2.70 ± 0.34 pmol/L: 134-141 d; 7.07 ± 1.57 pmol/L) and control (122-128 d; 3.36 ± 0.56 pmol/L: 134-141 d; 10.78 ± 2.88 pmol/L) groups. Combined adrenal weight was higher (p < 0.005) in the PR group (130 ± 10 mg/kg) compared with controls (80 ± 1 mg/kg) at 140 d of gestation, and plasma cortisol concentrations were also higher (p < 0.02) in PR than control fetuses between 127 and 141 d of gestation. These changes imply that the fetal hypothalamopituitary-adrenal axis is operating at a new central set point in the growth-restricted fetus.|
|Keywords:||Pituitary-Adrenal System; Pituitary Gland, Anterior; Fetal Blood; Placenta; Animals; Sheep; Oxygen; Hydrocortisone; Pro-Opiomelanocortin; RNA, Messenger; Regression Analysis; Embryonic and Fetal Development; Gestational Age; Pregnancy; Partial Pressure; Female; Adrenocorticotropic Hormone|
|Appears in Collections:||Obstetrics and Gynaecology publications|
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