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Differential Expression of Transforming Growth Factor-ß1 and Transforming Growth Factor-ß Receptors in Myometrium of Women With Failed Induction of Labor, No Labor, and Preterm Labor

Department of Obsterics and Gynecology, University of Florida College of Medicine, Gainesville, Florida; cheginin{at}obgyn.med.ufl.edu

Chunfeng Ma, MD, PhD

John Davis, MD

Patrick Duff, MD

Cesar Rosa, MD

Department of Obsterics and Gynecology, University of Florida College of Medicine, Gainesville, Florida

Objective: Comparative analysis of transforming growth factor-ß1 (TGF-ß1) and TGF-ß 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-ß1, and TGF-ß type I and type II receptor mRNA expression. Tissue sections were prepared from paraffin-embedded specimens and immunostained for TGF-ß1 and receptor proteins using specific polycolonal antibodies. The data were analyzed by unpaired Student t test and Kruskal-Wallis analysis of variance.

Results: Myometrium from women who had unsuccessful labor induction expressed higher levels of TGF-ß1 mRNA (2.21 ± 0.28 x 10⁶ copies/µg of total cellular RNA) than those with preterm labor (4.53 ± 0.2 x 10⁵ copies), or without labor [3.13 ± 2.6 x 10⁴ copies (P < .05)]. The level of TGF-ß 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 10⁵ copies) compared with those from unsuccessful labor induction (3.42 ± x 10⁶ copies) or without labor (9.65 ± 3.2 x 10⁵ copies). Immunoreactive TGF-ß1 and TGF-ß receptor proteins were present in all myometrial tissues, and their intensity reflected that of the mRNA expression in these tissues.

Conclusion: TGF-ß1 and TFG-ß 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-ß is a key regulator of tissue remodeling which is central to initiation of normal labor, alterations in TGF-ß and/or TGF-ß receptor expression may lead to changes in the outcome of labor, at least at the myometrial level.

Key Words: TGF-ß • TGF-ß receptors • expression • myometrium • labor

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