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J Clin Endocrinol Metab. 2010 Dec;95(12):E437-47. doi: 10.1210/jc.2010-1541. Epub 2010 Sep 15.

Effects of medroxyprogesterone acetate on gene expression in myometrial explants from pregnant women.

Author information

1
Department of Obstetrics and Gynaecology, University of Cambridge, Box 223, Cambridge CB2 0SW, United Kingdom. yc265@cam.ac.uk

Abstract

CONTEXT:

Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy, in part through controlling myometrial gene expression.

OBJECTIVE:

The objective of the study was to use expression microarray and quantitative reverse transcriptase-PCR (qRT-PCR) validation to determine the changes in gene expression induced by prolonged exposure of human myometrium to a synthetic progestogen.

DESIGN:

Myometrial explants, obtained at elective cesarean section (n=9), were maintained in culture, under 0.6 g tension, for 65 h in the presence of medroxyprogesterone acetate (100 nm) or vehicle. Expression array was performed using Illumina beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) by qRT-PCR.

RESULTS:

The 114 significantly regulated transcripts were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004), and cytokine activity genes (P=0.008). Thirty-four transcripts were validated using qRT-PCR in explants obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes that have been well characterized as progesterone sensitive (IL-1B, IL-6, PTGS2, and GJA1). However, the top and sixth most down-regulated transcripts encoded two cytokines, IL-11 and IL-24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3- and 2.2-fold down-regulated, both P<0.001).

CONCLUSIONS:

Medroxyprogesterone acetate controls expression of multiple genes in myometrium, including many that have not previously been characterized as progestogen regulated in this tissue, including IL-11 and IL-24. It is plausible that proteins encoded by some of these genes may have important but as yet uncharacterized effects in controlling human parturition.

PMID:
20843944
DOI:
10.1210/jc.2010-1541
[Indexed for MEDLINE]

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