The prevention of uterine infection is critical to appropriate fetal development and term delivery. The innate immune system is one component of the uterine environment and has a role in prevention of uterine infection. Natural antimicrobials are innate immune molecules with anti-bacterial, anti-viral and anti-fungal activity. We discuss two groups of natural antimicrobials in relation to pregnancy: (i) the defensins; and (ii) the whey acidic protein motif containing proteins, secretory leukocyte protease inhibitor (SLPI) and elafin. Human beta-defensins (HBD) 1-3 are expressed by placental and chorion trophoblast, amnion epithelium and decidua in term and preterm pregnancy. Elafin shows a similar pattern of localisation while SLPI is produced only by amnion epithelium and decidua. Evidence suggests that there is aberrant production of some natural antimicrobials in pathologic conditions of pregnancy. In preterm premature rupture of membranes (PPROM) levels of SLPI and elafin are reduced in amniotic fluid and fetal membranes, respectively. Elafin and HBD3 increase in chorioamnionitis and levels of the alpha-defensins, HNP1-3, increase in maternal plasma and amniotic fluid in women affected by microbial invasion of the uterus. In vitro culture studies have suggested a mechanism for increased production of natural antimicrobials in chorioamnionitis. Elafin, SLPI, HBD2 and 3 are all upregulated by inflammatory molecules in cells derived from gestational tissues. In summary, production of natural antimicrobials at key sites within the pregnant uterus suggests an important role in prevention of uterine infection during pregnancy and labour. Aberrant production of these molecules in PPROM and chorioamnionitis suggests that they also have a role in pathologic conditions. In particular, upregulation of these molecules by inflammatory molecules present in chorioamnionitis will ensure a robust response to infection.

Preterm birth associated with infection is a major clinical problem. We hypothesized that this condition is associated with altered expression of natural antimicrobial molecules (beta-defensins (HBD), elafin). Therefore, we examined expression of these molecules and their regulation by proinflammatory cytokines in placentae and fetal membranes from term pregnancy. HBD1-3 and elafin were localized by immunohistochemistry in fetal membranes and placenta. Real-time quantitative PCR was used to examine mRNA expression in primary trophoblast cells treated with inflammatory molecules. HBD1-3 and elafin were immunolocalized to placental and chorion trophoblast layers of fetal membranes and placenta. Immunoreactivity was also observed in amnion epithelium and decidua. No differences were noted between samples from women who were not in labour compared to those in active labour. In in vitro cultures of primary trophoblast cells, HBD2 and elafin mRNA expression was upregulated by the proinflammatory cytokine, IL-1beta. These results suggest that the chorion and placental trophoblast layers may be key barriers to the progression of infection in the pregnant uterus. Natural antimicrobial expression may be altered in response to inflammatory mediator expression associated with the onset of labour and/or uterine infection, providing increased protection when the uterus may be particularly susceptible to infection.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n = 8), isocaloric-sucrose/pair-feeding (n = 8) or water (n = 2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography-flame ionization detection and confirmed by gas chromatography-mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n = 3 fetuses). For meconium of the ethanol offspring (n = 25 fetuses) compared with the sucrose offspring (n = 23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium. total FAEE concentration and both body weight and brain weight.

Journal of Obstetrics and Gynaecology ResearchVolume 31, Issue 6 p. 492-499 Fetal signals and parturition John R. G. Challis, Corresponding Author John R. G. Challis Departments of Physiology, Medicine and Obstetrics and Gynecology, University of Toronto, CIHR Group in Fetal Development and Health Toronto, CanadaDr John R. G. Challis, Room 109, Simcoe Hall, 27 King's College Circle, University of Toronto, Toronto, Ontario, M5S 1A1, Canada. Email: j.challis@utoronto.caSearch for more papers by this authorFrank H. Bloomfield, Frank H. Bloomfield Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorAlan D. Bocking, Alan D. Bocking Departments of Physiology, Obstetrics and Gynecology, University of Toronto,Search for more papers by this authorValentina Casciani, Valentina Casciani Departments of Physiology,Search for more papers by this authorHiroshi Chisaka, Hiroshi Chisaka Departments of Physiology,Search for more papers by this authorKristin Connor, Kristin Connor Departments of Physiology,Search for more papers by this authorXuesen Dong, Xuesen Dong Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; andSearch for more papers by this authorPeter Gluckman, Peter Gluckman Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorJane E. Harding, Jane E. Harding Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorJim Johnstone, Jim Johnstone Departments of Physiology,Search for more papers by this authorWei Li, Wei Li Departments of Physiology,Search for more papers by this authorStephen Lye, Stephen Lye Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaSearch for more papers by this authorKunihiro Okamura, Kunihiro Okamura Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; andSearch for more papers by this authorMarina Premyslova, Marina Premyslova Departments of Physiology,Search for more papers by this author John R. G. Challis, Corresponding Author John R. G. Challis Departments of Physiology, Medicine and Obstetrics and Gynecology, University of Toronto, CIHR Group in Fetal Development and Health Toronto, CanadaDr John R. G. Challis, Room 109, Simcoe Hall, 27 King's College Circle, University of Toronto, Toronto, Ontario, M5S 1A1, Canada. Email: j.challis@utoronto.caSearch for more papers by this authorFrank H. Bloomfield, Frank H. Bloomfield Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorAlan D. Bocking, Alan D. Bocking Departments of Physiology, Obstetrics and Gynecology, University of Toronto,Search for more papers by this authorValentina Casciani, Valentina Casciani Departments of Physiology,Search for more papers by this authorHiroshi Chisaka, Hiroshi Chisaka Departments of Physiology,Search for more papers by this authorKristin Connor, Kristin Connor Departments of Physiology,Search for more papers by this authorXuesen Dong, Xuesen Dong Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; andSearch for more papers by this authorPeter Gluckman, Peter Gluckman Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorJane E. Harding, Jane E. Harding Liggins Institute, University of Auckland, New Zealand;Search for more papers by this authorJim Johnstone, Jim Johnstone Departments of Physiology,Search for more papers by this authorWei Li, Wei Li Departments of Physiology,Search for more papers by this authorStephen Lye, Stephen Lye Departments of Physiology, Obstetrics and Gynecology, University of Toronto, Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, CanadaSearch for more papers by this authorKunihiro Okamura, Kunihiro Okamura Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; andSearch for more papers by this authorMarina Premyslova, Marina Premyslova Departments of Physiology,Search for more papers by this author First published: 22 November 2005 https://doi.org/10.1111/j.1447-0756.2005.00342.xCitations: 57Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Objective: This cohort study investigated potential clinical and biochemical predictors of subsequent preterm birth in women presenting with threatened preterm labor.Study Design and Setting: Subjects were 218 pregnant women admitted to hospital with a diagnosis of threatened preterm labor at 22-36 weeks gestation. Exclusion criteria were multiple pregnancy, fetal anomalies, diabetes mellitus, abruptio placenta, preeclampsia, intrauterine growth restriction, cervical dilatation > 4 cm, and clinical signs of infection. Analyses used logistic regression.Results: The presence of ruptured membranes was the best predictor of birth within 48 hours. Other important predictors were maternal white blood cell count at 22-27 weeks gestation and maternal adrenocorticotropin and corticotropin-releasing hormone concentrations at 28-36 weeks gestation.Conclusion: Subclinical infection may be an important etiologic factor in preterm births of gestational age < 28 weeks. For those at greater than or equal to28 weeks gestation, the findings support the etiologic role of activation of the fetal and/or maternal hypothalamic pituitary adrenal axis leading to preterm birth. (C) 2005 Elsevier Inc. All rights reserved.