Journal of the Endocrine Society · 2023
High Expression of Adrenal Cortisol Synthases Is Acquired After Intrauterine Inflammation in Periviable Sheep Fetuses.
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Sato Shinichi, Watanabe Shimpei, Saito Yuya, Takanashi Aika, Ikeda Hideyuki, Sakurai Yoshie, Koshinami Shouta, Kumagai Yusaku, Usuda Haruo, Hanita Takushi, Kikuchi Atsuo, Saito Masatoshi
Аннотация
CONTEXT: Intrauterine inflammation, a representative stressor for the fetus, has been shown to alter the hypothalamus-pituitary-adrenal (HPA) axis reactivity in preterm fetuses and increase postnatal cortisol production. However, the mechanism of this alteration has not yet been elucidated.
OBJECTIVE: We aimed to clarify the effects of endotoxin-induced intrauterine inflammation on the HPA axis of periviable sheep fetuses.
METHODS: Fetal sheep (0.63 term) were divided into 2 groups: (1) the endotoxin group, in which the endotoxin was injected into the amniotic fluid; and (2) the control group, in which the saline solution was injected instead. A corticotropin-releasing hormone (CRH) challenge test was performed on the third day after injection to evaluate the cortisol-producing capacity of each group. Gene expression levels in the fetal adrenal glands of each group were analyzed by RNA-seq.
RESULTS: The cortisol levels were significantly higher in the endotoxin group than in the control group after CRH challenge (P = .02). There were no significant differences in the responsiveness of adrenocorticotropin and cortisone between the 2 groups. Gene expression levels of the following enzymes involved in cortisol synthesis were significantly elevated in the endotoxin group: cytochrome P450 family (CYP) 11 subfamily A member 1 (log2FC 1.75), CYP 17 subfamily A member 1 (log2FC 3.41), 3β-hydroxysteroid dehydrogenase type I (log2FC 1.13), steroidogenic acute regulatory protein (log2FC 1.09), and CYP 21 (log2FC 0.89).
CONCLUSION: Periviable fetuses exposed to inflammation in utero have altered the responsiveness of the HPA axis with increased expression of enzymes involved in cortisol synthesis in the adrenal gland.
OBJECTIVE: We aimed to clarify the effects of endotoxin-induced intrauterine inflammation on the HPA axis of periviable sheep fetuses.
METHODS: Fetal sheep (0.63 term) were divided into 2 groups: (1) the endotoxin group, in which the endotoxin was injected into the amniotic fluid; and (2) the control group, in which the saline solution was injected instead. A corticotropin-releasing hormone (CRH) challenge test was performed on the third day after injection to evaluate the cortisol-producing capacity of each group. Gene expression levels in the fetal adrenal glands of each group were analyzed by RNA-seq.
RESULTS: The cortisol levels were significantly higher in the endotoxin group than in the control group after CRH challenge (P = .02). There were no significant differences in the responsiveness of adrenocorticotropin and cortisone between the 2 groups. Gene expression levels of the following enzymes involved in cortisol synthesis were significantly elevated in the endotoxin group: cytochrome P450 family (CYP) 11 subfamily A member 1 (log2FC 1.75), CYP 17 subfamily A member 1 (log2FC 3.41), 3β-hydroxysteroid dehydrogenase type I (log2FC 1.13), steroidogenic acute regulatory protein (log2FC 1.09), and CYP 21 (log2FC 0.89).
CONCLUSION: Periviable fetuses exposed to inflammation in utero have altered the responsiveness of the HPA axis with increased expression of enzymes involved in cortisol synthesis in the adrenal gland.