Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/120680
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Type: Journal article
Title: Human placental androgen receptor variants: potential regulators of male fetal growth
Author: Meakin, A.
Saif, Z.
Tuck, A.
Clifton, V.
Citation: Placenta, 2019; 80:18-26
Publisher: Elsevier
Issue Date: 2019
ISSN: 0143-4004
1532-3102
Statement of
Responsibility: 
Ashley S.Meakin, Zarqa Saif, Astrud R.Tuck, Vicki L.Clifton
Abstract: INTRODUCTION:Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but the regulatory mechanisms underlying these differences remain unknown. We propose that these growth outcomes may be due to sex-specific differences in androgen sensitivity - giving rise to altered growth signalling pathways - mediated by the differential expression of placental androgen receptor (AR) variants. METHODS:Placental protein and mRNA were used to identify AR protein variant levels and AR-downstream target gene expression, and were then analysed against neonatal measurements. Dihydrotestosterone (DHT)-induced AR protein variant expression and downstream growth factors were examined in vitro. RESULTS:Four known AR variants (AR-FL, AR-V1, AR-V7, and AR-45), and three unknown proteins (120, 90 and 55 kDa) immunoreactive to the anti-AR antibody were identified in human placentae. Male placentae from controlled asthmatic pregnancies had increased AR-45 and decreased AR-V1 and AR-V7 nuclear expression. Increased nuclear AR-45 expression was associated with increased insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF-binding protein 5 (IGFBP-5) mRNA expression and normal male growth. AR-45 mRNA and protein did not change in the presence of uncontrolled maternal asthma and associated with an increase in small for gestational (SGA) male fetuses. In vitro DHT stimulation increased AR-45 protein and IGF-1R and IGFBP-5 mRNA expression. CONCLUSIONS:Collectively, our data shows altered AR protein expression and downstream signalling targets may contribute to sex-specific fetal growth outcomes in response to an adverse environment, and that AR-45 appears central in mediating these changes.
Keywords: Androgen receptor; Asthma; Fetal growth; Placenta; Pregnancy; Sex
Rights: © 2019 Elsevier Ltd. All rights reserved.
RMID: 0030112796
DOI: 10.1016/j.placenta.2019.03.012
Grant ID: http://purl.org/au-research/grants/nhmrc/1136100
http://purl.org/au-research/grants/nhmrc/1041918
Appears in Collections:Paediatrics publications

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