Chorioamnionitis reduces placental endocrine functions: the role of bacterial lipopolysaccharide and superoxide anion

Abstract

Chorioamnionitis has been shown to be one of the most important factors in inducing preterm delivery. The present study was undertaken to examine the effects of chorioamnionitis on placental endocrine functions. Preterm placentas with histologic chorioamnionitis produced smaller amounts of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) than those without chorioamnionitis (P < 0.001). To examine the mechanism involved in the suppression of placental endocrine functions induced by chorioamnionitis, we initially confirmed the expression of lipopolysaccharide (LPS) receptor, i.e. the CD14 molecule, on trophoblasts by Northern blot analysis and immunohistochemistry. We then stimulated purified trophoblasts with LPS, which is the major agent which induces inflammatory responses in the host via the LPS receptor. The trophoblasts stimulated with LPS produced reduced amounts of hCG, hPL, and progesterone in a time- and dose-dependent fashion in spite of the induced manganese-superoxide dismutase (SOD) synthesis. Stimulation of trophoblasts with hypoxanthine and xanthine oxidase resulted in suppressed hCG production, while the simultaneous addition of SOD into the culture medium reversed the suppression of hCG production. LPS in the placenta with chorioamnionitis might directly stimulate trophoblasts through the LPS receptor (CD14), thus reducing placental endocrine functions. Superoxide anions which exogenously act on trophoblasts might be generated by simultaneous stimulation of neutrophils and monocytes at the feto-maternal interface by LPS, and additively reduce placental endocrine functions.

Mitochondrial manganese superoxide dismutase mRNA expression in human chorioamniotic membranes and its association with labor, inflammation, and infection

“…It has been suggested that increased ROS production triggers cellular antioxidant defence mechanisms, and up-regulation of MnSOD expression may be protective against cell injury caused by inflammation and oxidative stress[48,49]. Indeed, treatment with antioxidants can effectively block innate and adaptive immune responses through the following mechanisms: 1) inhibiting LPS-induced TLR-4 and NF-kB signaling and IL-8 transactivation[87]; 2) suppressing LPS-stimulated generation of proinflammatory cytokines (TNF-α, IL-1β) and ROS $({\text{NO}}_2^{-}\text{and}{\mathrm{normalO}}_2^{-})$[98]; 3) reducing cytotoxic T-cell response and allograft rejection[99]; or 4) generating antigen-specific hyporesponsiveness of T-cells[89].…”

Inflammatory Responses in Embryonal Cardiomyocytes Exposed to LPS Challenge. An In Vitro Model of Deciphering the Effects of LPS on the Heart

“…In this context is opportune to mention that LPS may affect indirectly the fetus through its action on placenta, *Address correspondence to this autho at the Department of Human Anatomy and Histology, University of Bari, P.zza G. Cesare, 11; I-70124 Bari, Italy; Tel: ++39-080-5478351; Fax: ++39-080-5478327; E-mail: ma.panaro@anatomia.uniba.it by promoting both ROS release from the neutrophils and monocytes of the organ [19] and the prostaglandins release [20]. In addition LPS may also affect directly the embryo since it is able to cross the placental barrier.…”

Chorioamnionitis: A Risk Factor for Fetal and Neonatal Morbidity

“…Histologically demonstrated CA is reported to be associated with fetal growth retardation in term and preterm infants, presumably due to a reduction in placental hormone release [23,24].…”