Protein Expression of Aryl Hydrocarbon Receptors in Human Placentas from Mild Preeclamptic and Early Pregnancies

Hao, Kehong; Zhou, Qian; He, Qizhi; Zheng, Jing; Wang, Kai

doi:10.5772/32038

Cited by 3 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IDO is primarily expressed in the trophoblast and endothelial cells in the human placenta (Hönig et al, 2004), which was also seen in our AhR studies in which the syncytiotrophoblast and endothelium were the only placental cells to express AhR (Jiang et al, 2010;Hao et al, 2012). Thus, together with the fact that the activation of AhR induces IDO expression in human dendritic cells and mouse spleen and lung (Vogel et al, 2008), we speculate that AhR is likely to mediate IDO expression, which suppressed immunoresponses in association with the induction of T reg cells expressing the transcription factor Foxp3 (Mellor et al, 2002;Sun et al, 2011).…”

Section: Ahr Mediates the Expression Of Ido In The Human Placentasupporting

confidence: 80%

“…The activation of AhR by environmental pollutants like dioxin can induce profound immunosuppression, which is tightly involved in the induction of T reg cells (Marshall and Kerkvliet, 2010). Our previous data showed that AhR is highly expressed in the human placenta, especially in the syncytiotrophoblast, during both the first and third trimesters (Jiang et al, 2010;Hao et al, 2012). Its expression pattern from the first to third trimesters is highly similar to that of indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolising cytosolic enzyme, which plays an important role in maternal-foetal tolerance through the regulation of T reg cells differentiation (Hönig et al, 2004;Sedlmayr, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Possible role of the ‘IDO‐AhR axis’ in maternal‐foetal tolerance

Hao

Zhou

Chen

et al. 2013

Cell Biology International

Self Cite

View full text Add to dashboard Cite

The induction and maintenance of immunologic tolerance at the feto-maternal interface is necessary for a successful pregnancy. The most accepted hypothesis for the mechanism underlying this tolerance is that pregnancy-induced foetal antigen-specific maternal T regulatory (T(reg) ) cells mediate maternal tolerance to the foetus. The aryl hydrocarbon receptor (AhR), which is highly expressed in the placenta, is widely studied in female reproductive biology and immunology. Activation of AhR can promote immune tolerance by controlling the differentiation of T(reg) cells in some autoimmune disorders. However, the specific mechanisms underlying tolerance are poorly understood. Indoleamine 2,3-dioxygenase (IDO) is the initial and rate-limiting enzyme of tryptophan catabolism in human placental trophoblasts. IDO produces kynurenine, an endogenous AhR ligand that directly activates AhR and is proposed to be central to the establishment and maintenance of immunologic tolerance at the maternal-foetal interface. We propose that kynurenine activates AhR, leading to the AhR-dependent T(reg) cells generation, which in turn critically regulates immunological tolerance at the feto-maternal interface. This hypothesis must be tested and the proof of this hypothesis may provide a potential therapeutic target for the treatment of infertility and other adverse pregnancy outcomes resulted from inadequate immunological tolerance at the feto-maternal interface.

show abstract

Section: Ahr Mediates the Expression Of Ido In The Human Placentasupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Possible role of the ‘IDO‐AhR axis’ in maternal‐foetal tolerance

Hao

Zhou

Chen

et al. 2013

Cell Biology International

Self Cite

View full text Add to dashboard Cite

show abstract

“…These FT placentas were collected from patients with induced abortion at the gestational age of 6-8 weeks, as described elsewhere (Hao et al 2012). These FT placentas were collected from patients with induced abortion at the gestational age of 6-8 weeks, as described elsewhere (Hao et al 2012).…”

Section: Collection Of Placental Tissuesmentioning

confidence: 99%

Expression of G-Protein Subunit α-14 Is Increased in Human Placentas from Preeclamptic Pregnancies

Zhao

Zou

et al. 2014

J Histochem Cytochem.

Self Cite

View full text Add to dashboard Cite

G-proteins mediate cellular function upon interaction with G-protein coupled receptors. Of the 16 mammalian G-protein α subunits identified, G-protein subunit α-11 (GNA11) and -14 (GNA14) have been implicated in modulating hypertension and endothelial function. However, little is known about their expression and roles in human placentas. Here, we examined GNA11 and GNA14 protein expression in first trimester (FT), normal term (NT), and severe preeclamptic (sPE) human placentas as well as in NT human umbilical cords. We found that GNA11 and GNA14 were immunolocalized primarily in trophoblasts, villous stromal cells, and endothelial cells in placentas as well as in endothelial and/or smooth muscle cells of the umbilical cord artery and vein. Western blotting revealed that the GNA14, but not GNA11, protein levels were increased (2.5-2.9 fold; p<0.01) in sPE vs. NT placentas. GNA11 protein was detected only in NT, but not FT, placentas, whereas GNA14 protein levels were increased (7.7-10.6 fold; p<0.01) in NT vs. FT placentas. Thus, GNA11 and GNA14 may mediate the function of several cell types in placentas. Moreover, the high expression of GNA14 in sPE placentas may also imply its importance in sPE pregnancies as in the other hypertension-related disorders.

show abstract

“…We have recently reported abundant AhR protein expression in human placentas and in several fetal organs [31,32]. These observations strongly suggest that human placentas and those fetal organs with high AhR expression are highly susceptible to AhR ligands.…”

Section: Ahr and Pregnancymentioning

confidence: 98%

“…Both COX2 [8, 9,44,45] and AhR [31,32] are highly expressed in human placentas. In addition, COX2 is highly present in amniotic membrane [8,9,44,45].…”

Section: Ahr and Inflammationmentioning

confidence: 99%

A possible role of aryl hydrocarbon receptor in spontaneous preterm birth

Wang

Zou

et al. 2015

Medical Hypotheses

Self Cite

View full text Add to dashboard Cite

Preterm birth (PTB) is defined as birth before 37 weeks of gestation and is a leading cause of neonatal mortality and morbidity. To date, the etiology of spontaneous PTB (sPTB) remains unclear; however, intrauterine bacterial infection-induced inflammation is considered to be one of the major triggers. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor. Upon activation, AhR signaling mediates many biological processes. AhR is abundantly expressed in human placentas, primarily in trophoblasts, and several fetal organs and tissues. The activation of AhR signaling can modulate inflammatory responses via promoting production of pro-inflammatory cytokines by the placenta and fetal membranes. These cytokines could enhance expression and/or activity of cyclooxygenase-2 (COX2) in human trophoblasts and amniotic epithelia, which in turn stimulate synthesis and release of prostaglandins (PGs; e.g., PGE2 and PGF2α). Given the discovery of a number of natural and endogenous AhR ligands in human, we hypothesize that in a subset of patients with high AhR expression in placentas and fetal membranes, repeated exposure to these AhR ligands hyperactivates AhR, inducing hyperactivation of the cytokines/COX2/PGs pathway, resulting in myometrial contractions, ultimately leading to sPTB. We further hypothesize that hyperactivation of this AhR pathway can induce sPTB either directly or in synergy with the bacterial infection. Proof of this hypothesis may provide a novel mechanism underlying sPTB.

show abstract

Protein Expression of Aryl Hydrocarbon Receptors in Human Placentas from Mild Preeclamptic and Early Pregnancies

Cited by 3 publications

References 16 publications

Possible role of the ‘IDO‐AhR axis’ in maternal‐foetal tolerance

Possible role of the ‘IDO‐AhR axis’ in maternal‐foetal tolerance

Expression of G-Protein Subunit α-14 Is Increased in Human Placentas from Preeclamptic Pregnancies

A possible role of aryl hydrocarbon receptor in spontaneous preterm birth

Contact Info

Product

Resources

About