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Maternal Obesity and Clucocorticoids...

Ghnenis, Adel.

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Maternal Obesity and Clucocorticoids Metabolism: The Effect of Excess Cortisol in the Myocardium of Adult Offspring.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Maternal Obesity and Clucocorticoids Metabolism: The Effect of Excess Cortisol in the Myocardium of Adult Offspring./
作者:	Ghnenis, Adel.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
面頁冊數:	143 p.
附註:	Source: Dissertation Abstracts International, Volume: 79-09(E), Section: B.
Contained By:	Dissertation Abstracts International79-09B(E).
標題:	Animal sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10286790
ISBN:	9780355855838

Maternal Obesity and Clucocorticoids Metabolism: The Effect of Excess Cortisol in the Myocardium of Adult Offspring.
Ghnenis, Adel.

Maternal Obesity and Clucocorticoids Metabolism: The Effect of Excess Cortisol in the Myocardium of Adult Offspring. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 143 p.

Source: Dissertation Abstracts International, Volume: 79-09(E), Section: B.

Thesis (Ph.D.)--University of Wyoming, 2017.

Human epidemiological studies and animal experiments have shown that exposure to excessive circulating nutrients and/or glucocorticoids during pregnancy predisposes offspring to obesity, hypertension, and cardiovascular anomalies later in life. Data from our lab show that obese pregnant ewes (MO) and their fetuses display markedly elevated blood cortisol levels from mid to late gestation. While the maternal cortisol increase was associated with elevated ACTH secretion, the fetal cortisol rise occurred in the absence of a corresponding increase in fetal ACTH release, suggesting the possibility of a non-adrenal source. We have previously reported myocardial inflammation and fibrosis, as well as cardiac dysfunction in late-term fetuses gestated by MO ewes, in association with chronically elevated blood cortisol. Further, data from our lab and others have suggested a link between elevated cortisol exposure in utero and hypertension and cardiovascular disease. Using our ovine model of MO, two studies were conducted: first to determine the source of the fetal cortisol increase, and whether it was of fetal or maternal origin. Results showed that at day 135 of gestation (0.9G), maternal and fetal plasma cortisol and fetal plasma cortisone were increased (P<0.05) in MO vs CON groups. A significant positive correlation (P<0.05) between maternal plasma cortisol and fetal plasma cortisol, between maternal plasma cortisol and fetal plasma cortisone, and between fetal cortisone and cortisol concentrations were observed. Protein expression of 11? hydroxysteroid dehydrogenase 2 (11?-HSD2) in cotyledon tissues was increased (P<0.05) in MO compared to CON fetuses. The expression of 11?-HSD1 and its cofactor hexose-6-phosphate dehydrogenase (H6PD) in the liver and perirenal fat were higher (P<0.05) in MO compared to CON fetuses. The second study was conducted to examine the effect of MO on the myocardium of adult male offspring. Myocardial collagen content and collagen-crosslinking were greater (P<0.05) in MO compared to CON offspring in association with increased mRNA and protein expression of glucocorticoid receptors (GR). mRNA expression for proinflammatory cytokines: cluster of differentiation (CD)-68, transforming growth factor (TGF)-?1, and tumor necrosis factor (TNF)-? were increased (P < 0.05), and protein expression of CD-68, TGF-?1, and TNF-? tended to increase (P<0.10) in MO vs. CON offspring. These data provide evidence that increased placental conversion of maternal cortisol of MO mothers to cortisone leads to the observed elevation in fetal blood cortisone, which can then be converted to active cortisol by the liver and perirenal fat depots. MO-induced programming of elevated cortisol, myocardial inflammation, and fibrosis in adult male offspring potentially through increased GR. These may predispose offspring to metabolic dysfunction and cardiovascular disease in postnatal life.

ISBN: 9780355855838Subjects--Topical Terms:

3174829
Animal sciences.

Maternal Obesity and Clucocorticoids Metabolism: The Effect of Excess Cortisol in the Myocardium of Adult Offspring.
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