Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood
IntroductionMaternal 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 develo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1122432/full |
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| author | Mark H. Oliver Anne L. Jaquiery Kristin L. Connor Hui Hui Phua Jane E. Harding Eric B. Thorstensen Frank H. Bloomfield |
| author_facet | Mark H. Oliver Anne L. Jaquiery Kristin L. Connor Hui Hui Phua Jane E. Harding Eric B. Thorstensen Frank H. Bloomfield |
| author_sort | Mark H. Oliver |
| collection | DOAJ |
| description | IntroductionMaternal 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.MethodsEwes were undernourished from 61 days before to 30 days after conception (‘PCUN’) or fed ad libitum (‘N’). mRNA expression in the fetal adrenal gland of ACTH receptor (ACTHR), steroidogenic acute regulatory protein (STAR), cytochrome P450 17A1 (CYP17A1), 11beta-hydroxysteroid-dehydrogenase type 2 (11βHSD2), insulin-like growth factor-2 (IGF2), and in the fetal hippocampus of 11βHSD1, 11βHSD2, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) 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 ACTHR, STAR and CYP17A1 were determined in adult adrenals.ResultsFetal adrenal STAR, CYP17A1 and IGF2 mRNA expression were not different between groups in early gestation but were higher in PCUN than N at 131 days’ gestation (all p<0.01). PCUN reduced fetal hippocampal MR and GR 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 ACTHR, STAR, and CYP17A1 mRNA expression were not affected by PCUN.ConclusionsWe 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. |
| first_indexed | 2024-04-10T18:19:41Z |
| format | Article |
| id | doaj.art-fa998262683441e19db687b6c0060785 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T18:19:41Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-fa998262683441e19db687b6c00607852023-02-02T07:34:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11224321122432Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthoodMark H. Oliver0Anne L. Jaquiery1Kristin L. Connor2Hui Hui Phua3Jane E. Harding4Eric B. Thorstensen5Frank H. Bloomfield6Liggins Institute, University of Auckland, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New ZealandDepartment of Health Sciences, Carleton University, Ottawa, ON, CanadaLiggins Institute, University of Auckland, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New ZealandIntroductionMaternal 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.MethodsEwes were undernourished from 61 days before to 30 days after conception (‘PCUN’) or fed ad libitum (‘N’). mRNA expression in the fetal adrenal gland of ACTH receptor (ACTHR), steroidogenic acute regulatory protein (STAR), cytochrome P450 17A1 (CYP17A1), 11beta-hydroxysteroid-dehydrogenase type 2 (11βHSD2), insulin-like growth factor-2 (IGF2), and in the fetal hippocampus of 11βHSD1, 11βHSD2, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) 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 ACTHR, STAR and CYP17A1 were determined in adult adrenals.ResultsFetal adrenal STAR, CYP17A1 and IGF2 mRNA expression were not different between groups in early gestation but were higher in PCUN than N at 131 days’ gestation (all p<0.01). PCUN reduced fetal hippocampal MR and GR 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 ACTHR, STAR, and CYP17A1 mRNA expression were not affected by PCUN.ConclusionsWe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1122432/fullprogramminglong-termoutcomesadrenalcortisol |
| spellingShingle | Mark H. Oliver Anne L. Jaquiery Kristin L. Connor Hui Hui Phua Jane E. Harding Eric B. Thorstensen Frank H. Bloomfield Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood Frontiers in Endocrinology programming long-term outcomes adrenal cortisol |
| title | Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood |
| title_full | Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood |
| title_fullStr | Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood |
| title_full_unstemmed | Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood |
| title_short | Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood |
| title_sort | effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid late gestation through to adulthood |
| topic | programming long-term outcomes adrenal cortisol |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1122432/full |
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