Fetal androgen exposure is a determinant of adult male metabolic health

Katarzyna  Siemienowicz; Panagiotis Filis; Sophie Shaw; Alex Douglas; Jennifer  Thomas; Sally  Mulroy; Forbes Howie; Paul A Fowler; W. Colin Duncan; Mick T Rae

doi:10.1038/s41598-019-56790-4

Fetal androgen exposure is a determinant of adult male metabolic health

Katarzyna Siemienowicz, Panagiotis Filis, Sophie Shaw, Alex Douglas, Jennifer Thomas, Sally Mulroy, Forbes Howie, Paul A Fowler , W. Colin Duncan, Mick T Rae^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.

Original language	English
Article number	20195
Journal	Scientific Reports
Volume	9
DOIs	https://doi.org/10.1038/s41598-019-56790-4
Publication status	Published - 27 Dec 2019

Bibliographical note

This work was funded by Medical Research Council (MRC) project grant
(G0901807) to WCD and MTR, and MRC project grant MR/P011535/1 (To MTR, PAF and WCD).

Keywords

developmental biology
disease model
Dyslipidaemias
endocrine system and metabolic diseases
endocrinology
metabolic diseases
metabolism
physiology

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Paul Alfred François Fowler
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Translational Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Academic

Centre for Genome-Enabled Biology and Medicine
Elaina Susan Renata Collie-Duguid (Manager)
School of Medicine, Medical Sciences & Nutrition
Research Facilities: Facility

Cite this

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title = "Fetal androgen exposure is a determinant of adult male metabolic health",

abstract = "Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.",

keywords = "developmental biology, disease model, Dyslipidaemias, endocrine system and metabolic diseases, endocrinology, metabolic diseases, metabolism, physiology",

author = "Katarzyna Siemienowicz and Panagiotis Filis and Sophie Shaw and Alex Douglas and Jennifer Thomas and Sally Mulroy and Forbes Howie and Fowler, {Paul A} and Duncan, {W. Colin} and Rae, {Mick T}",

note = "This work was funded by Medical Research Council (MRC) project grant (G0901807) to WCD and MTR, and MRC project grant MR/P011535/1 (To MTR, PAF and WCD).",

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doi = "10.1038/s41598-019-56790-4",

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T1 - Fetal androgen exposure is a determinant of adult male metabolic health

AU - Siemienowicz, Katarzyna

AU - Filis, Panagiotis

AU - Shaw, Sophie

AU - Douglas, Alex

AU - Thomas, Jennifer

AU - Mulroy, Sally

AU - Howie, Forbes

AU - Fowler , Paul A

AU - Duncan, W. Colin

AU - Rae, Mick T

N1 - This work was funded by Medical Research Council (MRC) project grant (G0901807) to WCD and MTR, and MRC project grant MR/P011535/1 (To MTR, PAF and WCD).

PY - 2019/12/27

Y1 - 2019/12/27

N2 - Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.

AB - Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.

KW - developmental biology

KW - disease model

KW - Dyslipidaemias

KW - endocrine system and metabolic diseases

KW - endocrinology

KW - metabolic diseases

KW - metabolism

KW - physiology

U2 - 10.1038/s41598-019-56790-4

DO - 10.1038/s41598-019-56790-4

M3 - Article

C2 - 31882954

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 20195

ER -

Fetal androgen exposure is a determinant of adult male metabolic health

Abstract

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Keywords

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Paul Alfred François Fowler

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