The expression of transforming growth factor beta in pregnant rat myometrium is hormone and stretch dependent.
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 beta (TGFbeta) 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 TGFbetas. The expression of TGFbeta1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfbeta1-3 genes were expressed differentially in pregnant myometrium. Tgfbeta2 gene was not affected by pregnancy, whereas the Tgfbeta1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfbeta3 gene expression throughout pregnancy. Tgfbeta3 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 Tgfbeta3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20-23) caused a significant decrease in the expression of Tgfbeta3 gene. In addition, Tgfbeta3 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 TGFbeta family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction.
Shynlova
Oksana
O
Samuel Lunenfeld Research Institute at Mount Sinai, Mount Sinai Hospital, 600 University Avenue, Suite 870, Toronto, Ontario, Canada M5G 1X5.
Tsui
Prudence
P
Dorogin
Anna
A
Langille
B Lowell
BL
Lye
Stephen J
SJ
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020073:Gravidity; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D015735:Mifepristone; D017258:Medroxyprogesterone Acetate