Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene.

Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB.

Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway.

Objective: Infection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment.

Study Design: Inflammatory environment was simulated for UtSM cells by coculturing them with monocyte lineage (THP1) cells.

1,25-Dihydroxyvitamin D deficiency is associated with preterm birth in African American and Caucasian women.

Vitamin (vit) D deficiency and preterm birth (PTB) are more prevalent among African American (AA) women compared to caucasian (Cau) women. Because vit D is important in regulating cell-mediated immune responses, vit D insufficiency or deficiency during pregnancy may enhance inflammation in pregnant women and increase the risk of PTB. In this study, circulatory levels of 25-hydroxy (OH) and 1,25-dihydroxy (OH)2 vit D were measured using chemiluminescence and radioimmunoassay techniques, respectively, in AA (n = 108) and Cau (n = 84) women who delivered at term and preterm.

Vitamin D elicits anti-inflammatory response, inhibits contractile-associated proteins, and modulates Toll-like receptors in human myometrial cells.

Infection during pregnancy triggers inflammation, which can increase myometrial contractions and the risk of premature labor and delivery. In this study, we assessed the effects of vitamin D, an anti-inflammatory ligand on cytokines, chemokines, toll-like receptors, and contractile-associated proteins on immortalized human myometrial smooth muscle (UtSM) cells stimulated with lipopolysaccharide (LPS), a bacterial endotoxin, or interleukin (IL)-1β and measured Toll-like receptor (TLR)-10 expression in pregnant myometrial tissues. A superarray analysis revealed downregulation of the chemokines monocyte chemoattractant protein (MCP)-1, Chemokine (C-X-C motif) ligand (CXCL)-10, CXCL-11, and chemokine (C-X3-C motif) ligand (CX3CL)-1; the proinflammatory cytokines IL-13 and tumor necrosis factor (TNF)-α; the TLR-4 and -5 and triggering receptor expressed on myeloid cells (TREM)-2 and upregulation of the anti-inflammatory cytokine IL-10, as well as Toll interacting protein (TOLLIP) and TREM-1 in vitamin D-treated UtSM cells.

A single-nucleotide polymorphism in the fetal catechol-O-methyltransferase gene is associated with spontaneous preterm birth in African Americans.

Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA and Cau.

Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase.

Objective: To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro.

Design: Laboratory study.

Setting: University hospitals.

Elevated expression of catechol-O-methyltransferase is associated with labor and increased prostaglandin E(2) production by human fetal membranes.

Objective: The purpose of this study was to evaluate the expression and function of catechol-O-methyltransferase in human fetal membranes at term.

Study Design: Fetal membranes obtained from women between 38-42 weeks of gestation, after (1) vaginal delivery with spontaneous labor and (2) prelabor elective cesarean section (no labor), were assayed for catechol-O-methyltransferase expression using quantitative real-time polymerase chain reaction analysis, immunohistochemistry, and Western blot analysis. Prostaglandin E(2) secretion from amnion and choriodecidua explants treated with or without catechol-O-methyltransferase inhibitor was assayed by enzyme-linked immunosorbent analysis.

Evidence for decreased calcitonin gene-related peptide (CGRP) receptors and compromised responsiveness to CGRP of fetoplacental vessels in preeclamptic pregnancies.

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory peptide, and its concentration is increased in both maternal and fetal circulation during late pregnancy. The present study was designed to investigate the expression of CGRP receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity modifying protein 1 (RAMP1), and the relaxation response to CGRP in fetoplacental vessels from normotensive pregnant women and women with preeclampsia. Results showed that: 1) mRNA for both CRLR and RAMP1 was expressed in fetoplacental vessels from normal pregnancies; however, these mRNA expressions were substantially reduced in the vessels from preeclamptic women; 2) CRLR and RAMP1 proteins were abundantly expressed in the endothelium and smooth muscle layer of the fetoplacental vessels, as well as the trophoblast cells in normal placentas.

Progesterone upregulates calcitonin gene-related peptide and adrenomedullin receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker rat uterine smooth muscle cell line.

Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM), two potent smooth-muscle relaxants, have been shown to cause uterine relaxation. Both CGRP- and AM-binding sites in the uterus increase during pregnancy and decrease at labor and postpartum. These changes in binding sites appear to be related to the changes in calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 1 (RAMP1), RAMP2, and RAMP3 mRNA levels.