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The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

Franks, Stephen; Rae, Mick T; Grace, Cathal; Hogg, Kirsten; Wilson, Lisa Marie; McHaffie, Sophie L; Ramaswamy, Seshadri; MacCallum, Janis; Connolly, Fiona; McNeilly, Alan S; Duncan, Colin

Authors

Stephen Franks

Cathal Grace

Kirsten Hogg

Lisa Marie Wilson

Sophie L McHaffie

Seshadri Ramaswamy

Fiona Connolly

Alan S McNeilly

Colin Duncan



Abstract

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P

Citation

Franks, S., Rae, M. T., Grace, C., Hogg, K., Wilson, L. M., McHaffie, S. L., …Duncan, C. (2013). The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS). PLOS ONE, 8(2), Article e56263. https://doi.org/10.1371/journal.pone.0056263

Journal Article Type Article
Acceptance Date Jan 7, 2013
Online Publication Date Feb 15, 2013
Publication Date Feb 15, 2013
Deposit Date Mar 27, 2014
Publicly Available Date Mar 27, 2014
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 2
Article Number e56263
DOI https://doi.org/10.1371/journal.pone.0056263
Keywords polycystic ovary syndrome (PCOS); insulin signalling; pancreatic morphology; quantitative (Q) RT-PCR; western blotting; androgen over-exposure;
Public URL http://researchrepository.napier.ac.uk/id/eprint/6686
Publisher URL http://dx.doi.org/10.1371/journal.pone.0056263

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