母羊围孕期营养不良对子代从中孕期到成年期皮质醇调节的影响。

Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood.

机构信息

Liggins Institute, University of Auckland, Auckland, New Zealand.

Department of Health Sciences, Carleton University, Ottawa, ON, Canada.

出版信息

Front Endocrinol (Lausanne). 2023 Feb 2;14:1122432. doi: 10.3389/fendo.2023.1122432. eCollection 2023.

DOI:10.3389/fendo.2023.1122432

PMID:36817600

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9932192/

Abstract

INTRODUCTION

Maternal periconceptional undernutrition (PCUN) alters fetal hypothalamic-pituitary-adrenal axis (HPAA) function and placental glucocorticoid metabolism in sheep. The effects of PCUN on HPAA function in adult life are not known. We investigated the effects of PCUN on fetal adrenal development across gestation and on cortisol regulation in adult offspring.

METHODS

Ewes were undernourished from 61 days before to 30 days after conception ('PCUN') or fed ('N'). mRNA expression in the fetal adrenal gland of ACTH receptor (), steroidogenic acute regulatory protein (, cytochrome P450 17A1 (, 11beta-hydroxysteroid-dehydrogenase type 2 (, insulin-like growth factor-2 (, and in the fetal hippocampus of , , mineralocorticoid receptor () and glucocorticoid receptor () was determined at 50 (adrenal only), 85, 120 and 131 days of gestation (term=148 days). In adult offspring (≥ 3 years, N; 10 female, 5 male, PCUN; 10 female, 10 male) a combined arginine vasopressin (AVP, 0.1 μg/kg) and corticotropin-releasing hormone (CRH, 0.5 μg/kg) challenge and a metyrapone (40 mg/kg) challenge were undertaken. mRNA expression of , and were determined in adult adrenals.

RESULTS

Fetal adrenal , and mRNA expression were not different between groups in early gestation but were higher in PCUN than N at 131 days' gestation (all <0.01). PCUN reduced fetal hippocampal and mRNA expression by 50% at 85 day, but not in later gestation. Adult offspring plasma cortisol responses to AVP+CRH or metyrapone were not different between groups. Plasma ACTH response to AVP+CRH was lower in PCUN males but ACTH response to metyrapone was not different between groups. Adult adrenal , , and mRNA expression were not affected by PCUN.

CONCLUSIONS

We conclude that the effects of PCUN on fetal HPAA function that became apparent in late gestation, are not reflected in adrenal cortisol secretion in mid-adulthood.

摘要

简介

母体围孕期营养不良（PCUN）改变了绵羊胎儿下丘脑-垂体-肾上腺轴（HPAA）功能和胎盘糖皮质激素代谢。PCUN 对成年后 HPAA 功能的影响尚不清楚。我们研究了 PCUN 对胎儿肾上腺发育的影响以及对成年后代皮质醇调节的影响。

方法

从受孕前 61 天到受孕后 30 天，对母羊进行限食（“PCUN”）或正常饲养（“N”）。在妊娠 50 天（仅肾上腺，N；10 只雌性，5 只雄性，PCUN；10 只雌性，10 只雄性）、85 天、120 天和 131 天（足月=148 天）时，测定胎儿肾上腺中的促肾上腺皮质激素受体（）、类固醇急性调节蛋白（、细胞色素 P450 17A1（、11β-羟类固醇脱氢酶 2 型（、胰岛素样生长因子-2（和胎儿海马中的、、盐皮质激素受体（）和糖皮质激素受体（mRNA 表达。在成年后代（≥ 3 岁，N；10 只雌性，5 只雄性，PCUN；10 只雌性，10 只雄性）中，进行了精氨酸加压素（AVP，0.1μg/kg）和促肾上腺皮质激素释放激素（CRH，0.5μg/kg）联合冲击试验和甲吡酮（40mg/kg）冲击试验。测定了成年肾上腺中的、和 mRNA 表达。

结果

妊娠早期，两组胎儿肾上腺、和 mRNA 表达无差异，但 131 天时 PCUN 组高于 N 组（均<0.01）。PCUN 在妊娠 85 天时使胎儿海马中的和 mRNA 表达减少了 50%，但在后期妊娠时没有变化。AVP+CRH 或甲吡酮对成年后代的皮质醇反应无差异。PCUN 雄性的 AVP+CRH 刺激后的血浆 ACTH 反应较低，但两组间的甲吡酮刺激后的 ACTH 反应无差异。成年肾上腺、、和 mRNA 表达不受 PCUN 影响。