GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner.

OBJECTIVE: The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes. STUDY DESIGN: Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter. RESULTS: Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM. CONCLUSION: Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.

Association of oestrogen-containing contraceptives with pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex--findings from a survey.

OBJECTIVES About 30-40% of women with tuberous sclerosis complex (TSC) develop pulmonary lymphangioleiomyomatosis (LAM). Oestrogen seems to be involved in LAM pathogenesis and oestrogen-containing contraception should be avoided in women with known LAM. However, there is very little data on the use of contraceptives in TSC patients. METHODS We conducted a survey on the use of contraception and disease characteristics. The questionnaire was forwarded to all adult female TSC patients listed in the database of a German patient organisation. RESULTS Data from 39 such patients could be analysed. Of these, 15 were diagnosed with LAM. Twenty-five patients (65%) confirmed current or past use of oestrogen-containing contraceptives. We found a suggestive correlation between the history of oestrogen-containing contraception, and LAM (Odds ratio: 6.500; 95% confidence interval: 1.199-35.230). However, oestrogen use was not associated with LAM complications. CONCLUSIONS Based on our findings, oestrogen-containing contraceptives should be resorted to by these patients only with great caution, and avoided whenever possible.

Complete hydatidiform mole in a perimenopausal woman with a subsequent severe thyriotoxicosis.

INTRODUCTION: Gestational trophoblastic disease is one form of abnormal pregnancy, with a median maternal age of 27-28 years. One complication of trophoblastic disease is the development of a secondary hyperthyroidism, which resolves rapidly after evacuation of the hydatidiform mole. CASE REPORT: We report a case of a 53-year-old woman presenting with a complete hydatidiform mole and who developed a severe thyrotoxicosis after suction evacuation of the hydatidiform mole. CONCLUSION: A severe thyriotoxicosis can occur even after surgical evacuation of the mole. Therefore, evaluation of the thyroid function prior to operation, especially with a high quantitative hCG, should be performed to avoid severe complications.

Inhibition of toll-like receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus.

Human plasmacytoid dendritic cells (PDC) are key sentinels alerting both innate and adaptive immune responses through production of huge amounts of alpha/beta interferon (IFN). IFN induction in PDC is triggered by outside-in signal transduction pathways through Toll-like receptor 7 (TLR7) and TLR9 as well as by recognition of cytosolic virus-specific patterns. TLR7 and TLR9 ligands include single-stranded RNA and CpG-rich DNA, respectively, as well as synthetic derivatives thereof which are being evaluated as therapeutic immune modulators promoting Th1 immune responses. Here, we identify the first viruses able to block IFN production by PDC. Both TLR-dependent and -independent IFN responses are abolished in human PDC infected with clinical isolates of respiratory syncytial virus (RSV), RSV strain A2, and measles virus Schwarz, in contrast to RSV strain Long, which we previously identified as a potent IFN inducer in human PDC (Hornung et al., J. Immunol. 173:5935-5943, 2004). Notably, IFN synthesis of PDC activated by the TLR7 and TLR9 agonists resiquimod (R848) and CpG oligodeoxynucleotide 2216 is switched off by subsequent infection by RSV A2 and measles virus. The capacity of RSV and measles virus of human PDC to shut down IFN production should contribute to the characteristic features of these viruses, such as Th2-biased immune pathology, immune suppression, and superinfection.