Increased Expression of Pro‐Inflammatory Cytokines in Placentas of Women Undergoing Spontaneous Preterm Delivery or Premature Rupture of Membranes

El-Shazly, Sherief; Makhseed, M.; Azizieh, Fawaz

doi:10.1111/j.1600-0897.2004.00181.x

Cited by 107 publications

(78 citation statements)

References 36 publications

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“…4,5). Placental expression of inflammatory cytokines is part of normal immune function during pregnancy (32), but overexuberant cytokine responses are also known to play a key role in adverse outcomes of pregnancy (33)(34)(35)(36). Analysis of pregnant mice has shown that IL-4 is a major placental cytokine, with expression increasing across gestation (37).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

183

118

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The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas −/− for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated −/− placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated −/− placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1−/− versus Cyp27b1+/+ placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1−/− placentas. Similar results for IL-6 expression were observed with placentas −/− for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D3, suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.

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Section: Discussionmentioning

confidence: 99%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

183

118

View full text Add to dashboard Cite

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“…(25) Alternatively, systemic inflammation initiated by periodontal disease might contribute to both the increase in stillbirth and neonatal mortality noted in this study. (25)(26)(27)(28) In both developed and developing countries, periodontal disease is an attractive candidate for intervention, especially because it is readily identified and treated. Periodontal disease treatment has included antiseptic mouthwash, several antibiotics, and periodontal cleaning and plaque removal (scaling and root planing).…”

Section: Discussionmentioning

confidence: 99%

Periodontal disease and adverse birth outcomes: a study from Pakistan

Mobeen

Jehan

Banday

et al. 2008

American Journal of Obstetrics and Gynecology

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OBJECTIVES-Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. METHODS-Enrollment occurred at 20-26 wks.A study dentist performed the periodontal examination to assess probing depth (PD), clinical attachment level (CAL), gingivitis index (GI) and plaque index (PI). Outcomes included stillbirth, neonatal mortality, <32 wk preterm birth (PTB), 32-36 wk PTB, and low birthweight (LBW), and are presented for increasing periodontal disease severity by quartiles (Q1-4).RESULTS-Dental examinations and outcome data were completed for 1152 women. 81% were multiparous with a mean age of 27 yrs. 33% had no education. Dental caries were present in 47%, missing teeth in 27%, and 92% had no dental care in the last year. Periodontal disease was common: 87% had ≥ 4 teeth with a PD of >3mm, 54% had ≥4 teeth with a PI = 3, and 58% had ≥ 4 teeth with a GI = 3. In general, as the measure of periodontal disease increased, stillbirth, PTB <32 wks and neonatal mortality also increased. Late PTB and LBW were not related to measures of periodontal disease. Adjustment for demographic characteristics did not significantly change the relationships.

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“…Excessive Th1 cytokine production, on the other hand, has been shown to evoke rejection responses directed against fetoplacenal semiallografts [61]. Th1/Th2 imbalance has been found in association with multiple failures of recurrent spontaneous a b o r t i o n s [ 3 0 , 3 1 ] , p r e e c l a m p s i a [ 3 2 -3 4 ] , intrauterine growth retardation [35], preterm delivery, and premature rupture of membranes [36,37]. In this study, a significant increase in the Th1/ Th2 ratio was observed in the interspecific p r e g n a n c y g r o u p w h e n c o m p a r e d t o t h e intraspecific pregnancy group, suggesting a bias state for Th1/Th2 in interspecific pregnancies.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive amounts of Th1 cytokines could hamper the immunological tolerance of the female to the foreign antigens of the fetus. Increased expression of Th1 cytokines or an increased ratio of Th1/Th2 cytokines has been observed at the feto-maternal interface in abortionprone mice [29], and this occurs not only at the fetomaternal interface but also in the peripheral blood in many human pregnancy failures, such as r e c u r r e n t s p o n t a n e o u s a b o r t i o n [ 3 0 , 3 1 ] , preeclampsia [32][33][34], intrauterine growth retardation [35], preterm delivery, and premature rupture of membranes [36,37]. Shift of the Th1/ Th2 balance to Th1 dominance contributes to the failure of pregnancy.…”

mentioning

confidence: 99%

Increased Th1/Th2 (IFN-.GAMMA./IL-4) Cytokine mRNA Ratio of Rat Embryos in the Pregnant Mouse Uterus

et al. 2007

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Abstract. Somatic cell nuclei can be dedifferentiated in ooplasm from another species, and interspecies cloned embryos can be implanted into the uteri of surrogates. However, no full pregnancies have been achieved through interspecific mammalian cloning. Rat blastocysts transferred into mouse uteri provide a unique model for studying the causes of interspecific pregnancy failure. In this study, intraspecific pregnancy (mouse-mouse) and interspecific pregnancy (rat-mouse) models were established. On Day 9 of pregnancy, the fetoplacental units were separated from the uterine implantation sites and the expression of messenger (m)RNA was quantitated by realtime PCR. We compared the mRNA expression levels of type-1 T helper (Th1) and type-2 T helper (Th2) cytokines, interferon-gamma (IFN-γ), and interleukin-4 (IL-4) in fetoplacental units between intraspecific and interspecific pregnancy groups. The mRNA expression of IFN-γ in the fetoplacental units of the interspecific pregnancy group was significantly higher than that of the intraspecific pregnancy group (P<0.05). The mRNA expression of IL-4 in the interspecific pregnancy group was significantly lower than that in the intraspecific pregnancy group (P<0.05). We also analyzed the ratio of IFN-γ/IL-4 mRNA, and an increased IFN-γ/IL-4 mRNA ratio was observed in the interspecific pregnancy compared with that in the intraspecific pregnancy group. The IFN-γ and IL-4 mRNA expressions indicate that there is a Th1/Th2 imbalance in the feto-maternal interface of interspecific pregnancies. Bias of Th1 cytokine dominance may be a barrier to reproductive success between species. Key words: Interferon (IFN)-γ, Interleukin (IL)-4, Interspecific pregnancy, Mouse, Rat (J. Reprod. Dev. 53: [219][220][221][222][223][224][225][226][227][228] 2007) o far, somatic cell nuclear transfer (SCNT) has succeeded in generating live animals in many species, including sheep, cattle, mice, goats, pigs, rabbits, cats, rats, mules, horses, dogs, and ferrets [1][2][3][4]. However, it is impractical to clone endangered species by intraspecific SCNT because of insufficient numbers of oocytes and surrogate females. So, interspecific SCNT (iSCNT) has been explored to produce cloned offspring, and usually includes interspecific somatic cell nuclear transfer and interspecific pregnancy. In previous research, the oocytes of bovine, sheep, and rabbits have been used for iSCNT, and interspecific reconstructed embryos have been obtained [5][6][7][8][9][10][11][12][13]. Interspecific r e c o n s t r u c t e d e m b r y o s c a n i m p l a n t i n t o interspecific uteri, but only three speices have been successfully cloned by iSCNT [14][15][16]. Bovine ooplasm was capable of reprogramming the banteng [Bos javanicus, listed as a threatened

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Increased Expression of Pro‐Inflammatory Cytokines in Placentas of Women Undergoing Spontaneous Preterm Delivery or Premature Rupture of Membranes

Abstract: These data support our observation of a pro-inflammatory cytokine bias in women with PTD and PROM.

Cited by 107 publications

References 36 publications

Vitamin D and the Regulation of Placental Inflammation

Vitamin D and the Regulation of Placental Inflammation

Periodontal disease and adverse birth outcomes: a study from Pakistan

Increased Th1/Th2 (IFN-.GAMMA./IL-4) Cytokine mRNA Ratio of Rat Embryos in the Pregnant Mouse Uterus

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