Placenta-Specific Transcripts Containing Androgen Response Elements Are Altered In Silico by Male Growth Outcomes

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Meakin, Ashley S
Smith, Melanie
Morrison, Janna L
Roberts, Claire T
Lappas, Martha
Ellery, Stacey J
Holland, Olivia
Perkins, Anthony
McCracken, Sharon A
Flenady, Vicki
Clifton, Vicki L
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2024
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Abstract

A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th–30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th–30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th–30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.

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International Journal of Molecular Sciences

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25

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3

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The University of Queensland_NHMRC

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2006523

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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Meakin, AS; Smith, M; Morrison, JL; Roberts, CT; Lappas, M; Ellery, SJ; Holland, O; Perkins, A; McCracken, SA; Flenady, V; Clifton, VL, Placenta-Specific Transcripts Containing Androgen Response Elements Are Altered In Silico by Male Growth Outcomes, International Journal of Molecular Sciences, 2024, 25 (3), pp. 1688

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