Demonstration of Functional Cytokine-Placental Interactions: CSF-1 and GM-CSF Stimulate Human Cytotrophoblast Differentiation and Peptide Hormone Secretion

Mi, Garcia-Lloret; Dw, Morrish; Tg, Wegmann; Honoré, Louis H.; Ar, Turner; Guilbert, Larry J.

doi:10.1006/excr.1994.1232

Cited by 153 publications

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“…26 Indeed, GM-CSF receptor subunit GM-Rα is present on first trimester cytotrophoblast, extravillous trophoblasts, and at lower levels on the syncytiotrophoblast. 27 This way, GM-CSF is able to induce differentiation of villous cytotrophoblasts and to stimulate secretion of placental lactogen, human chorionic gonadotropin, 28 and IL-10, 29 which is considered to have a central role in suppressing the activities of pro-inflammatory Th1 cytokines. 30,31 In the light of these observations, enhanced release of GM-CSF and CCL5 in response to elevated maternal TNF-α may be interpreted as fetal attempt to protect the villous placenta from exaggerated maternal inflammation.…”

Section: Discussionmentioning

confidence: 99%

TNF-α alters the inflammatory secretion profile of human first trimester placenta

Siwetz

Blaschitz

El‐Heliebi

et al. 2016

Laboratory Investigation

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Implantation and subsequent placental development depend on a well-orchestrated interaction between fetal and maternal tissues, involving a fine balanced synergistic cross-talk of inflammatory and immune-modulating factors. Tumor necrosis factor (TNF)-α has been increasingly recognized as pivotal factor for successful pregnancy, although high maternal TNF-α levels are associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus. This study describes effects of exogenously applied TNF-α, mimicking increased maternal TNF-α levels, on the secretion profile of inflammation associated factors in human first trimester villous placenta. Conditioned culture media from first trimester villous placental explants were analyzed by inflammation antibody arrays and ELISA after 48 h culture in the presence or absence of TNF-α. Inflammation antibody arrays identified interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 2 (CCL2), CCL4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most abundantly secreted inflammation-associated factors under basal culture conditions. In the presence of TNF-α, secretion of GM-CSF, CCL5, and IL-10 increased, whereas IL-4 and macrophage CSF levels decreased compared with controls. ELISA analysis verified antibody arrays by showing significantly increased synthesis and release of GM-CSF and CCL5 by placental explants in response to TNF-α. Immunohistochemistry localized GM-CSF in the villous trophoblast compartment, whereas CCL5 was detected in maternal platelets adhering to perivillous fibrin deposits on the villous surface. mRNA-based in situ padlock probe approach localized GM-CSF and CCL5 transcripts in the villous trophoblast layer and the villous stroma. Results from this study suggest that the inflammatory secretion profile of human first trimester placenta shifts towards increased levels of GM-CSF, CCL5, and IL10 in response to elevated maternal TNF-α levels, whereas IL-6 and IL-8 remain unaffected. This shift may represent a protective mechanism by human first trimester villous placenta to sustain trophoblast function and dampen inflammatory processes in the intervillous space. Implantation and subsequent placenta development are mandatory steps for successful human pregnancy and depend on a well-orchestrated interaction between fetal and maternal tissues. Fetal-maternal interaction involves a fine balanced synergistic cross-talk of inflammaory and immune-modulating factors to allow maternal immune adaption and tolerance of the semiallogeneic fetus at the one hand, whereas maternal immune functions need to be maintained to fight off infections on the other hand. Various concepts and paradigms have been suggested trying to explain how the maternal immune system is modulated to guarantee a viable pregnancy. One of the proposed paradigms is based on studies by Wegmann et al, 1 describing a shift from an inflammatory T-helper 1 (Th1) cytokine profile to a rather anti-inflammatory T-helper 2 (Th2) profile. ...

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Section: Discussionmentioning

confidence: 99%

TNF-α alters the inflammatory secretion profile of human first trimester placenta

Siwetz

Blaschitz

El‐Heliebi

et al. 2016

Laboratory Investigation

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“…On the other hand, the endometrium is known to produce several cytokines and growth factors (e.g. leukemia inhibitory factor (LIF), macrophage-colony stimulating factor (M-CSF), epidermal growth factor (EGF)), that are known to modulate trophoblast differentiation and embryonic development (Benveniste et al 1978;Garcia-Lloret et al 1994;Hoshina et al 1985;Sawai et al 1995). Therefore it is highly conceivable, that a successful implantation will only take place when a good embryo giving the appropriate signals meets a responsive endometrium.…”

Section: The Embryo-endometrial Dialoguementioning

confidence: 99%

Is human chorionic gonadotropin directly involved in the regulation of human implantation?

Licht

Fluhr

Neuwinger³

et al. 2007

Molecular and Cellular Endocrinology

160

115

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Please cite this article as: Licht, P., Fluhr, H., Neuwinger, J., Wallwiener, D., Wildt, L., Is human chorionic gonadotropin directly involved in the regulation of human implantation? Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 SummaryThe regulation of human implantation is not fully understood. HCG as one of the earliest embryonal signals may be a major regulator in the parakrine embryoendometrial communication. The expression of full-length hCG/LH-receptor mRNA could be demonstrated in human endometrium throughout the follicular and secretory phase of the menstrual cycle. In contrast, in early pregnancy decidua only truncated variants could be detected. To investigate direct effects of hCG on the human endometrium, an intrauterine microdialysis device was developed to measure parakrine mediators within the uterine cavity in vivo. Using this system, hCG was applied in the secretory phase and the endometrial response was evaluated. The administration of hCG (500 IU/ml) provoked a significant inhibition of intrauterine IGFBP-1 and M-CSF, while LIF, VEGF and MMP-9 were significantly stimulated.Taken together there appear to be multiple direct effects of hCG on the endometrium that precede the classical endocrine role of the hormone.

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“…Indeed, PGE 2 stimulates GM-CSF production by peripheral blood lymphocytes both in the human (Fortin et al 1997) and in bovine (Emond et al 1998). GM-CSF is known to stimulate placento-fetal growth in several animal species (Chaouat et al 1990;Loke et al 1992;Garcia-Lloret et al 1994;de Moraes and Hansen 1997) The precise mechanisms by which PGE 2 is involved in porcine embryonic development are currently being investigated. CONCLUSION There was no synergism between folic acid supplements and conditioning of the uterus with dead semen on the reproductive performance or on the secretion of allantoic PGE2 at 30 d of gestation.…”

Section: Concentrations Of Prostaglandins In Allantoic Fluidmentioning

confidence: 99%

Reproductive performance and uterine prostaglandin secretion in gilts conditioned with dead semen and receiving dietary supplements of folic acid

Giguère¹,

Girard²,

Lambert³

et al. 2000

Can. J. Anim. Sci.

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. 2000. Reproductive performance and uterine prostaglandin secretion in gilts conditioned with dead semen and receiving dietary supplements of folic acid. Can. J. Anim. Sci. 80: 467-472. The effects of dietary supplements of folic acid at 0 (F-) or 15 ppm (F+) and of conditioning the uterus (C+) or not (C-) with an intrauterine infusion of dead semen on embryonic survival and prostaglandin E2 (PGE 2 ) concentrations in the allantoic fluid on day 30 of gestation were studied. Sixty-four F 1 crossbred gilts (Yorkshire × Landrace) were used in a 2 × 2 factorial design. The initiation of folate supplementation and the intrauterine infusion of dead semen were done at the estrus preceding the fertile mating. Folate status in serum was lower in F+ gilts than in F-gilts during the estrus cycle (folic acid × period interaction, P ≤ 0.007). Conditioning increased ovulation rate in F-gilts while it tended to decrease it in F+ gilts (interaction folic acid × conditioning, P ≤ 0.03). A similar interaction (P ≤ 0.02) was observed on the number of presumably live embryos at 30 d of gestation. Mean PGE 2 concentration in the allantoic fluid was not affected by treatments (P ≥ 0.44), but the frequency of sows having elevated allantoic PGE 2 (> 4 ng mL -1 ) tended to be higher (P ≤ 0.06) in F+ sows. Overall values of PGE 2 were correlated with total litter weight (R 2 =0.54). In conclusion, there was no synergism between folic acid supplements and conditioning of the uterus with dead semen on the reproductive performance or on the secretion of allantoic PGE 2 at 30 d of gestation. The secretion of allantoic PGE 2 appears as an important factor involved in the control of litter size and weight. infusion intra-utérine (C+) ou non (C-) de semence morte ont été mesurés sur la survie et le développement embryonnaire ainsi que sur la sécrétion utérine de prostaglandine E 2 (PGE 2 ) à 30 jours de gestation. A cet effet, soixante-quatre cochettes F 1 (Yorkshire-Landrace) ont été distribuées dans des traitements factoriels 2 × 2. L'infusion intra-utérine de semence morte et le début de la supplémentation en folate ont été faites à l'oestrus précé-dant la saillie fertile. Les concentrations de folates sériques étaient plus basses chez les truies F+ que chez les F-pendant le cycle oestral précédant la saillie féconde (interaction acide folique × période, P ≤ 0,007). Le conditionnement utérin a provoqué une augmentation du taux d'ovulation chez les cochettes F-alors qu'une diminution était observée chez les F+ (interaction acide folique × conditionnement, P ≤ 0,03). Une interaction similaire (P ≤ 0,02) a été observée sur le nombre d'embryons présumés vivants à 30 jours de gestation. Aucun effet (P ≥ 0,44) des traitements n'a été observé sur la PGE 2 dans le liquide allantoïdien mais la fréquence des taux supérieurs à 4 ng mL -1 avait tendance à être plus élevée (P ≤ 0,06) chez les truies F+ vs F-. Les valeurs de PGE 2 étaient corrélées avec le poids de la portée (R 2 = 0,54). En conclusion, il semble qu'il n'y ait pas d'avantage à combiner u...

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Demonstration of Functional Cytokine-Placental Interactions: CSF-1 and GM-CSF Stimulate Human Cytotrophoblast Differentiation and Peptide Hormone Secretion

Cited by 153 publications

References 0 publications

TNF-α alters the inflammatory secretion profile of human first trimester placenta

TNF-α alters the inflammatory secretion profile of human first trimester placenta

Is human chorionic gonadotropin directly involved in the regulation of human implantation?

Reproductive performance and uterine prostaglandin secretion in gilts conditioned with dead semen and receiving dietary supplements of folic acid

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