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Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

ABSTRACT: OBJECTIVES:l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. METHODS:Patients with SM (n?=?15) and RM (n?=?15) were compared with patients from healthy pregnancies (n?=?15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. RESULTS:Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. CONCLUSIONS:Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side.

SUBMITTER: Gratz MJ

PROVIDER: S-EPMC5958746 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

Gratz Michael J MJ Stavrou Stavroula S Kuhn Christina C Hofmann Simone S Hermelink Kerstin K Heidegger Helene H Hutter Stefan S Mayr Doris D Mahner Sven S Jeschke Udo U Vattai Aurelia A

Endocrine connections 20180423 5

<h4>Objectives</h4>l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D<sub>2</sub>-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls.<h4>Methods</h4>Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancie ...[more]

PMID: 29686031

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Project description:BackgroundWe recently demonstrated the increased abundance of anti-trophoblast antibodies (ATAB) in sera of patients with unexplained recurrent miscarriages (uRM). Further, the ATAB-positive sera bound to JEG-3 human choriocarcinoma cells in vitro, resulting in decreased productions of β-human chorionic gonadotropin (β-hCG) and progesterone in these cells. However, the specific antigenic epitopes of ATAB have remained unknown. Therefore, it was the aim of this study to determine specific targets of ATAB in uRM patients.MethodsPotential targets of ATAB were analyzed by 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry, and thereby identifying α-Enolase (ENO1). ATAB targeting of ENO1 was further confirmed in a competitive binding assay. Levels of anti-ENO1 antibodies as well as β-hCG and progesterone were quantified with enzyme-linked immunosorbent assay (ELISA). Additionally, expression of ENO1 was analyzed in first trimester placentas by immunohistochemistry and immunofluorescence analysis.FindingsWe here identified ENO1 as a prominent target of ATAB. Serum levels of anti-ENO1 antibodies were increased in ATAB-positive compared to ATAB-negative patients. Further, increased expression of ENO1 and its co-expression with β-arrestin was found in the extra villous trophoblasts of uRM patients in first trimester placentas. In vitro, anti-ENO1 antibodies decreased the secretion of β-hCG and progesterone in JEG-3 and primary human villous trophoblast cells.InterpretationSerum anti-ENO1 antibodies might be an autoimmune biomarker for uRM. Targeting the formation of anti-ENO1 antibodies or inhibition of ENO1 expression could potentially represent therapeutic strategies for these patients. FUND: All authors declare no conflict of interest. Yao Ye was supported by the China Scholarship Council. Hellen Ishikawa-Ankerhold and Christian Schulz were supported by the SFB914, projects Z01 and A10. None of the rest authors has any conflict of interest to declare.

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Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

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Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

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