The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Abstract

From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor b (TGFb) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFbs. The expression of TGFb1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfb1-3 genes were expressed differentially in pregnant myometrium. Tgfb2 gene was not affected by pregnancy, whereas the Tgfb1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfb3 gene expression throughout pregnancy. Tgfb3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfb3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20-23) caused a significant decrease in the expression of Tgfb3 gene. In addition, Tgfb3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFb family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction. Reproduction (2007) 134 503-511

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

“…Our data indicate similar effects of P4 and MPA on labor prevention. In our preliminary experiments, we confirmed that both drugs are equally effective in blocking term labor for at least 24 h, preventing increases in the expression of myometrial genes (22)(23)(24)(25). Animals (n ϭ 4 at each time point for each treatment) were killed on days 21-23 during labor in the vehicletreated group or days 21-24 in the P4-treated group.…”

The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth

“…The following mechanisms of disease have been implicated: 1) intrauterine infection/inflammation ; 2) uterine ischaemia [293][294][295][296][297][298][299][300][301][302][303][304][305][306][307]; 3) uterine overdistension [308][309][310][311][312][313][314][315][316][317][318][319][320][321][322][323][324][325][326][327]; 4) abnormal allogenic recognition [328][329][330][331][332][333][334][335]; 5) allergic-like reaction [336][337][338][339][340]; 6) cervical disease [341,…”

MiR‐98 is involved in rat embryo implantation by targeting Bcl‐xl

“…However, miR-98 expression showed a decreasing trend in the uterus of the ovariectomized pregnant rat treated by progesterone. It is different in gene expression patterns and hormonal levels in rat uterus between pregnancy and non-pregnancy [17,18], which may be one of the reasons that results in the contradictory results.…”