Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones

Chong, Hsu P., Cordeaux, Yolande, Ranjan, Yorain Sri, Richardson, Sylvia, Liquet, Benoit, Smith, Gordon C. S. and Charnock-Jones, David Stephen (2016) Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones. Aging Cell, 15 1: 177-180. doi:10.1111/acel.12406


Author Chong, Hsu P.
Cordeaux, Yolande
Ranjan, Yorain Sri
Richardson, Sylvia
Liquet, Benoit
Smith, Gordon C. S.
Charnock-Jones, David Stephen
Title Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones
Journal name Aging Cell   Check publisher's open access policy
ISSN 1474-9726
1474-9718
Publication date 2016-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1111/acel.12406
Open Access Status DOI
Volume 15
Issue 1
Start page 177
End page 180
Total pages 4
Place of publication Chichester, West Sussex United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Subject 1302 Ageing
1307 Cell Biology
Abstract In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week-old mice that had been treated with progesterone or vehicle containing implants from 8 to 36 weeks. Transcript profiling was carried out using Affymetrix Gene ST 1.1 arrays, and data were normalized. We identified 60 differentially regulated transcripts associated with advancing age (group 1). We validated these changes in group 2 (P for overlap = 5.8 × 10). Early ovariectomy prevented the age-related changes in myometrial transcript profile. Similarly, progesterone-mediated long-term ovarian suppression prevented the age-related changes in myometrial transcript profile. Interferon regulatory factor 7 (Irf7) mRNA was regulated by age and hormonal exposure, and was identified as a predicted regulator of the other differentially expressed transcripts by both promoter sequence and canonical pathway activation analysis (P = 8.47 × 10 and P < 10, respectively). Immunohistochemistry demonstrated IRF7 in both mouse and human myometrium. We conclude the following: (i) Myometrial aging in mice is associated with reproducible changes in transcript profile (ii) these changes can be prevented by interventions which inhibit cyclical changes in the female sex hormones; and (iii) IRF7 may be an important regulator of myometrial function and aging.
Formatted abstract
In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week-old mice that had been treated with progesterone or vehicle containing implants from 8 to 36 weeks. Transcript profiling was carried out using Affymetrix Gene ST 1.1 arrays, and data were normalized. We identified 60 differentially regulated transcripts associated with advancing age (group 1). We validated these changes in group 2 (P for overlap = 5.8 × 10−46). Early ovariectomy prevented the age-related changes in myometrial transcript profile. Similarly, progesterone-mediated long-term ovarian suppression prevented the age-related changes in myometrial transcript profile. Interferon regulatory factor 7 (Irf7) mRNA was regulated by age and hormonal exposure, and was identified as a predicted regulator of the other differentially expressed transcripts by both promoter sequence and canonical pathway activation analysis (P = 8.47 × 10−5 and P < 10−10, respectively). Immunohistochemistry demonstrated IRF7 in both mouse and human myometrium. We conclude the following: (i) Myometrial aging in mice is associated with reproducible changes in transcript profile; (ii) these changes can be prevented by interventions which inhibit cyclical changes in the female sex hormones; and (iii) IRF7 may be an important regulator of myometrial function and aging.
Keyword Steroid
Myometrium
Aging
Labor
IRF7
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Mathematics and Physics
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