Human myometrial adaptation to pregnancy: cDNA microarray gene expression profiling of myometrium from non‐pregnant and pregnant women

• Published in: Molecular human reproduction Vol. 9; no. 11; pp. 681 - 700
• Main Authors: Rehman, Khurram S., Yin, Su, Mayhew, Bobbie A., Word, R.Ann, Rainey, William E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2003; Oxford Publishing Limited (England)
• Subjects: Adaptation, Physiological; Biological and medical sciences; Blotting, Northern - methods; Down-Regulation; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Hormone metabolism and regulation; Humans; Key words: gene expression/microarray/myometrium/non‐pregnant/pregnant; Mammalian female genital system; Myometrium - chemistry; Myometrium - cytology; Myometrium - metabolism; Oligonucleotide Array Sequence Analysis; Pregnancy - genetics; Pregnancy - metabolism; Up-Regulation; Vertebrates: reproduction; Human; Myometrium; Estrogen; DNA chip; gene expressian/microarray/myometrium/non-pregnant/pregnant; Gene expression; Pregnancy; Plasminogen activator inhibitor 1; Insulin like growth factor; Regulation(control); Epidermal growth factor; Uterus; Complementary DNA; Female genital system; Female; Woman; Hormonal receptor
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/gag078

The human uterus undergoes profound physiological tissue remodelling during pregnancy. In the myometrium, altered gene expression must underlie these extensive molecular and structural changes. The purpose of this study was to compare expression profiles of pregnant and non‐pregnant myometrium, in order to identify genes that participate in this process. mRNA from 14 non‐pregnant and four pregnant human myometrial samples were analysed using a human UniGEM V microarray with 7075 cDNA elements. A total of 602 transcripts from the microarray were up‐regulated ≥2.0‐fold in pregnant myometrium, with 37 transcripts up‐regulated ≥4.0‐fold. In contrast, eight transcripts were down‐regulated ≥2.0‐fold in pregnancy. To ensure accurate representation of differential gene expression, Northern blot analyses using total RNA from 16 samples of non‐pregnant and pregnant myometrium were used to examine mRNA levels for four of the genes that were differentially expressed by microarray analysis, namely plasminogen activator inhibitor type 1 (PAI‐1), milk fat globule‐EGF factor 8 protein (MFGE8), secreted frizzled‐related protein 4 (sFRP4) and estrogen receptor α (ERα). On the microarray these transcripts were up‐regulated 7.5‐fold for PAI‐1 and 4.9‐fold for MFGE8 in pregnant myometrium, and down‐regulated 3.7‐fold for sFRP4 and 2.9‐fold for ERα in pregnancy. Northern blot analyses confirmed these changes. Our findings suggest that microarray technology is a useful tool for examining global changes in gene expression that occur as the myometrium differentiates from non‐pregnant to pregnant status. Defining these changes provides new insight into the structural and functional adaptations of human myometrium during pregnancy.