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A heretical view: rather than a solely placental protective function, placental 11β hydroxysteroid dehydrogenase 2 also provides substrate for fetal peripheral cortisol synthesis in obese pregnant ewes

Published online by Cambridge University Press:  10 March 2020

Adel B. Ghnenis Open the ORCID record for Adel B. Ghnenis [Opens in a new window] ,
John F. Odhiambo ,
Ashley M. Smith ,
Chris L. Pankey ,
Peter W. Nathanielsz  and
Stephen P. Ford
Adel B. Ghnenis*
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, TX77807, USA
John F. Odhiambo
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA Division of Agricultural and Food Sciences, Florida A&M University, Tallahassee, FL32307, USA
Ashley M. Smith
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA
Chris L. Pankey
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA
Peter W. Nathanielsz*
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA
Stephen P. Ford
Affiliation:
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY82071, USA
*
Address for correspondence: Adel B. Ghnenis, Department of Animal Science, 1000 E. University Avenue, University of Wyoming, Laramie, WY82071, USA. Email: [email protected]; Peter W. Nathanielsz, Department of Neuroscience & Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, 8447 Riverside Parkway, Bryan, TX77807, USA. Email: [email protected]
Address for correspondence: Adel B. Ghnenis, Department of Animal Science, 1000 E. University Avenue, University of Wyoming, Laramie, WY82071, USA. Email: [email protected]; Peter W. Nathanielsz, Department of Neuroscience & Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, 8447 Riverside Parkway, Bryan, TX77807, USA. Email: [email protected]
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Abstract

Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.

Keywords

Glucocorticoids11β hydroxysteroid dehydrogenasematernal obesityplacentafetal cortisol
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 1 , February 2021 , pp. 94 - 100
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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Footnotes

†

These authors contributed equally to this work.

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