Cytokines of the Placenta and Extra-placental Membranes: Biosynthesis, Secretion and Roles in Establishment of Pregnancy in Women

Bowen, J.M.; Chamley, Larry; Mitchell, Murray D.; Keelan, Jeffrey A.

doi:10.1053/plac.2001.0781

Cited by 219 publications

(171 citation statements)

References 217 publications

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“…This is relevant to the enlarged spongiotrophoblast layer in placentae from pregnant Nas1 -/-mice, which have enhanced mid-gestational fetal loss. Spongiotrophoblasts produce numerous proteins with endocrine activity, including cytokines, prolactin-like hormones and lactogens [35], which are essential for the maintenance and progression of pregnancy and development of the fetus [36][37][38]. Whilst the precise mechanism underlying the placental phenotype in Nas1 -/-mice is at present not clear, our data demonstrate maternal hyposulfataemia accompanies an enlarged spongiotrophoblast layer.…”

mentioning

confidence: 78%

Fetal Loss and Hyposulfataemia in Pregnant NaS1 Transporter Null Mice

Dawson

Sim

Simmons

et al. 2011

Journal of Reproduction and Development

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Abstract. Sulfate is important for growth and development, and is supplied from mother to fetus throughout pregnancy. We used NaS1 sulfate transporter null (Nas1 -/-) mice to investigate the role of NaS1 in maintaining sulfate homeostasis during pregnancy and to determine the physiological consequences of maternal hyposulfataemia on fetal, placental and postnatal growth. We show that maternal serum (≤0.5 mM), fetal serum (<0.1 mM) and amniotic fluid (≤0.5 mM) sulfate levels were significantly lower in pregnant Nas1 -/-mice when compared with maternal serum (≈2.0 mM), fetal serum (≈1.5 mM) and amniotic fluid (≈1.7 mM) sulfate levels in pregnant Nas1 +/+ mice. After 12 days of pregnancy, fetal reabsorptions led to markedly reduced (by ≥50%) fetal numbers in Nas1 -/-mice. Placental labyrinth and spongiotrophoblast layers were increased (by ≈140%) in pregnant Nas1 -/-mice when compared to pregnant Nas1 +/+ mice. Birth weights of progeny from female Nas1 -/-mice were increased (by ≈7%) when compared to progeny of Nas1 +/+ mice. These findings show that NaS1 is essential to maintain high maternal and fetal sulfate levels, which is important for maintaining pregnancy, placental development and normal birth weight. Key words: Placenta, Pregnancy, Sulfate (J. Reprod. Dev. 57: [444][445][446][447][448][449] 2011) ulfate (SO4 2-) is vital for many processes in fetal growth and development, including neurogenesis and steroid metabolism [1][2][3]. The ratio of sulfonated (inactive) to unconjugated (active) steroids has important implications for many of the steroid-responsive events that regulate placental and fetal growth [4]. For example, placental estradiol-3-sulfate is taken up by the fetal brain, where it is desulfonated by steroid sulfatase to estradiol, which acts as a potent stimulator of fetal adrenocorticotropin secretion and the hypothalamus-pituitary-adrenal axis [5]. In addition, sulfonation of structural components, such as heparan sulfate proteoglycans (HSPGs), is essential for the maintenance of normal structure and function of placental and fetal tissues [6]. Together, these findings demonstrate an important role for sulfate in maintaining steroid and glycosaminoglycan homeostasis in the developing fetus. SO4 2-is obtained from the diet and from the intracellular metabolism of methionine and cysteine [6]. Circulating SO4 2-levels are maintained by the NaS1 sulfate transporter which is expressed in the kidney where it mediates sulfate reabsorption [7]. During pregnancy, maternal blood sulfate levels increase by approximately 2-fold which provides an essential supply to the placenta and developing fetus [8][9][10][11]. This increase in circulating sulfate level is correlated with increased maternal renal sulfate reabsorption [9,12]. Since the fetus has a relatively low capacity to form sulfate from methionine and cysteine [13,14], most of its sulfate must come from the maternal circulating sulfate pool. These findings are relevant to the decreased fecundity of NaS1 knockout (Nas1 -/-) mice which exhibit bot...

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mentioning

confidence: 78%

Fetal Loss and Hyposulfataemia in Pregnant NaS1 Transporter Null Mice

Dawson

Sim

Simmons

et al. 2011

Journal of Reproduction and Development

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“…Various factors such as adhesion molecules 37 and cytokines 38 are involved in these processes. The defect of trophoblast invasion is related to human pregnancy complications such as pre-eclampsia and placenta increta.…”

Section: Discussionmentioning

confidence: 99%

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

Jin

et al. 2014

Cell Mol Immunol

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T helper 17 (Th17) cells have both regulatory and protective roles in physiological conditions. The Th17 subset and the cytokine interleukin-17A (IL-17A) have been implicated in the pathogenesis of certain autoimmune diseases, several types of cancer and allograft rejection. However, the role of Th17 cells at the maternal/fetal interface remains unknown. Here, we demonstrate that Th17 cells are present in decidua and are increased in the peripheral blood of 10 clinically normal pregnancies based on intracellular cytokine analysis. Our results suggest a potential role of Th17 cells in sustaining pregnancy in humans. Furthermore, we demonstrate that decidual stromal cells (DSCs) but not trophoblast cells recruit peripheral Th17 cells into the decidua by secreting CCL2. The recruited Th17 cells promote proliferation and invasion and inhibit the apoptosis of human trophoblast cells by secreting IL-17 during the first trimester of pregnancy. These findings indicate a novel role for Th17 cells in controlling the maternal-fetal relationship and placenta development.

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“…Increased cord serum inflammatory markers G Amarilyo et al role in pregnancy maintenance 15 and that the risk of the delivery of a SGA infant is associated with anti-inflammatory cytokine polymorphisms. 16 This may explain the report of increased interleukin-10 concentrations in the amniotic fluid in IUGR pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Increased cord serum inflammatory markers in small-for-gestational-age neonates

et al. 2010

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Objective: The pathological picture in ischemic tissue injury shares features with the inflammatory response. Hypoxia-mediated induction of interleukin-6 (IL-6) could set in motion the mechanisms limiting inflammation in ischemia. Intrauterine growth restriction (IUGR) represents a human model of chronic fetal hypoxia. The purpose of this study was a first-time exploration to determine whether cord blood obtained at the delivery of small-for-gestational-age (SGA) infants has increased concentrations of inflammatory markers.Study Design: Cord blood was collected from 20 SGA (term and nearterm) infants and 20 appropriate-for-gestational-age (AGA) controls. Infants exposed to maternal smoking, diabetes, maternal chronic diseases, or alcohol or drug use were excluded. Both groups had Apgar score X7 at 1 min with a normal cord pH (>7.25). Cord-serum cytokines and thrombopoietin (TPO) levels were measured by enzyme linked immunosorbent assay. C-reactive protein (CRP) was measured using a turbidometric immunoassay.Result: SGA infants had a significantly smaller birth weight than AGA controls, with a smaller gestation age by 1 week. There were significant elevations in IL-6, tumor necrosis factor (TNF-a), CRP and TPO in the SGA compared with the AGA group, which persisted in multiple regression analysis even after gestational age was taken into account. Conclusion:As hypothesized, significant increases in the cord blood concentrations of known inflammatory markers were found in SGA infants compared with the controls.

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Cytokines of the Placenta and Extra-placental Membranes: Biosynthesis, Secretion and Roles in Establishment of Pregnancy in Women

Cited by 219 publications

References 217 publications

Fetal Loss and Hyposulfataemia in Pregnant NaS1 Transporter Null Mice

Fetal Loss and Hyposulfataemia in Pregnant NaS1 Transporter Null Mice

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

Increased cord serum inflammatory markers in small-for-gestational-age neonates

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