Differential expression of transforming growth factor-beta 1 and transforming growth factor-beta receptors in myometrium of women with failed induction of labor, no labor, and preterm labor.

OBJECTIVE

Comparative analysis of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta receptor type I and type II messenger RNA (mRNA) and protein expression in myometrium of women who had unsuccessful labor induction, with those without labor or in preterm labor complicated by chorioamnionitis.

METHODS

Small segments of myometrium were collected from women who were undergoing cesarean delivery for unsuccessful labor induction (n = 5), elective cesarean without labor (n = 5), or cesarean delivery for complications related to preterm labor and chorioamnionitis (n = 5). Total RNA was isolated from these tissues and subjected to competitive quantitative reverse-transcription-polymerase chain reaction (Q-RT-PCR) to determine the level of TGF-beta 1, and TGF-beta type I and type II receptor mRNA expression. Tissue sections were prepared from paraffin-embedded specimens and immunostained for TGF-beta 1 and receptor proteins using specific polycolonal antibodies. The data were analyzed by impaired Student t test and Kruskal-Wallis analysis of variance.

RESULTS

Myometrium from women who had unsuccessful labor induction expressed higher levels of TGF-beta 1 mRNA (2.21 +/- 0.28 x 10(6) copies/microgram of total cellular RNA) than those with preterm labor (4.53 +/- 0.2 x 10(5) copies), or without labor [3.13 +/- 2.6 x 10(4) copies (P < .05)]. The level of TGF-beta type I receptor mRNA expression did not vary; however, type II receptor expression was significantly lower in myometrium from preterm labor (1.36 +/- 0.36 x 10(5) copies) compared with those from unsuccessful labor induction (3.42 +/- 0.42 x 10(6) copies) or without labor (9.65 +/- 3.2 x 10(5) copies). Immunoreactive TGF-beta 1 and TGF-beta receptor proteins were present in all myometrial tissues, and their intensity reflected that of the mRNA expression in these tissues.

CONCLUSION

TGF-beta 1 and TGF-beta type II receptors are expressed differently in myometrium of women who had unsuccessful labor induction compared with those without labor or with preterm labor complicated by chorioamnionitis. Because TGF-beta is a key regulator of tissue remodeling which is central to initiation of normal labor, alterations in TGF-beta and/or TGF-beta receptor expression may lead to changes in the outcome of labor, at least at the myometrial level.