Regulation and immunosuppressive properties of G-protein coupled estrogen receptor (GPER) in human placental syncytiotrophoblast — ASN Events
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  2. SRB Poster Session - Pregnancy/Parturition/Placenta
  3. Regulation and immunosuppressive properties of G-protein coupled estrogen receptor (GPER) in human placental syncytiotrophoblast

Regulation and immunosuppressive properties of G-protein coupled estrogen receptor (GPER) in human placental syncytiotrophoblast (#257)

Kaushik Maiti 1 , Simon Riley 2 , Kirsty Pringle 1 , Carolyn Mitchell 1 , Eng-Cheng Chan 1 , Jorge M. Tolosa 1 , Maria Bowman 1 , Roger Smith 1
  1. MBRC, John Hunter Hospital, New Lambton, NSW, Australia
  2. Obstetrics and Gynaecology , University of Edinburgh, Edinburgh, United Kingdom

In this study, we have investigated the expression, regulation and function of the plasma membrane bound GPER in human placental tissues.

We determined expression of GPER in term amnion, chorion, decidua and placental trophoblast by RT-PCR, western-blot and immuno-histochemistry. We also investigated expression of GPER in placental trophoblast from first and second trimester pregnancies. We have performed primary placental trophoblast cell cultures to determine the expression of GPER during the process of syncytialisation. To determin the effect of estrogen actions through the GPER on placental immune function we treated BeWo choriocarcinoma cells with estrogen and G1, a GPER specific agonist for 48 and 72 hrs and measured interleukin-10 (IL-10) in the media by ELISA.

The RT-PCR, western-blot and immuno-histochemistry data showed GPER is expressed in higher levels in placental trophoblast compared to  amnion, chorion and decidua. Additionally, immunohistochemistry data showed that GPER is expressed specifically in the apical membrane of syncytiotrophoblast in both term and earlier gestation placentas but, there were no differences in expression of GPER across gestation. In primary trophoblast culture, expression of GPER increased with time and with the formation of sycytium. Hypoxia induced factor 1-α (HIF1-α) a transcription factor, which regulates expression of GPR30 also increased in primary trophoblast culture with time. GPER is expressed in Bewo cells. Application of estrogen and G1(0.1uM) increased secreted IL-10 approximately 19.3 and 13.5 times respectively in BeWo cells at 72 hrs. G1 increased secretion of IL-10 in a dose dependant manner with a LogEC50 value of 8.03±0.19 in BeWo cells at 72 hrs.

Our study demonstrated that expression of GPER is restricted to the apical membrane of syncytiotrophoblast which may be regulated by HIF1 a. Estrogens acting via GPER stimulate production of the immunosuppressive cytokine IL-10 within trophoblastic cells.We conclude that estrogens active via GPER may regulate the immunosuppressive properties of syncytiotrophoblast during pregnancy by stimulating production of IL-10.


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