Thrombospondin-1 Expression in Human Myometrium before and during Pregnancy, before and during Labor, and in Human Myometrial Cells in Culture

• Published in: Biology of reproduction 1998-10, Vol.59 (4), p.862-870
• Main Authors: MORIMOTO, T, HEAD, J. R, MACDONALD, P. C, CASEY, M. L
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blotting, Northern; Cells, Cultured; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; In Situ Hybridization; Labor, Obstetric - metabolism; Mother. Fetoplacental unit. Mammary gland. Milk; Myometrium - cytology; Myometrium - metabolism; Pregnancy - metabolism; Pregnancy. Parturition. Lactation; RNA, Messenger - biosynthesis; Thrombospondin 1 - biosynthesis; Vertebrates: reproduction
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod59.4.862

The activation of latent transforming growth factor β (L-TGFβ) is essential for the action of TGFβ, which, in turn, is involved in the regulation of expression of some progesterone-responsive genes. One mechanism by which TGFβ is activated involves thrombospondin (TSP), a protein that binds extracellular proteins. Immunoreactive TSP (irTSP) protein and TSP-1 mRNA in myometrial tissues of ovulatory and pregnant women were localized by immunohistochemistry and in situ hybridization. IrTSP and TSP-1 mRNA were randomly distributed in myometrial smooth muscle cells of some, but not all, tissues of pregnant women at term before labor; but in some areas of most of these tissues, irTSP was intense and commonly localized extracellularly. Intense irTSP and TSP-1 mRNA in myocytes were more common in myometrium during labor. In myometrium from ovulatory women (n = 26), irTSP was localized primarily in vascular smooth muscle cells and was detected occasionally in scattered myocytes. Little TSP-1 mRNA was demonstrable by in situ hybridization in vessels or myocytes of myometrial tissue from ovulatory women (n = 7). By Northern analysis of total RNA, TSP-1 mRNA was detected in myometrial tissue of pregnant women and in human myometrial smooth muscle cells in culture. The levels of TSP-1 mRNA in myometrial tissues of pregnant women during labor (n = 18) were greater than those in myometrium at > 37 wk gestation before labor began (n = 25, p < 0.001). The ratios of TSP-1 to glyceraldehyde 3-phosphate dehydrogenase mRNAs in 3 myometrial tissues during oxytocin-induced labor were not statistically different from those in myometrium during spontaneous labor but were greater than those in myometrium before labor ( p < 0.05). The level of TSP-1 mRNA in confluent human myometrial cells in culture was relatively high, was increased by treatment with fetal bovine serum, and was decreased by treatment with platelet-derived growth factor or activators of adenylyl cyclase or protein kinase C. Myometrial cells in culture constitute a useful model for studying the regulation of TSP-1 gene expression in human myometrium.