The rat placental renin-angiotensin system - a gestational gene expression study.

BACKGROUND: The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta. METHODS: Whole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP). RESULTS: Six out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20. CONCLUSIONS: The current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies.

The TACI receptor regulates T-cell-independent marginal zone B cell responses through innate activation-induced cell death.

Activation-induced cell death (AICD) plays a critical role in immune homeostasis and tolerance. In T-cell-dependent humoral responses, AICD of B cells is initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B cells. In contrast, T-cell-independent B cell responses involve innate-type B lymphocytes, such as marginal zone (MZ) B cells, and little is known about the mechanisms that control AICD during innate B cell responses to Toll-like receptor (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4 activation in vivo. The transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate expression of both FasL and Fas on MZ B cells and also to repress inhibitors of Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role for TACI and its ligands in the regulation of AICD during T-cell-independent B cell responses.

Aard is specifically up-regulated in Sertoli cells during mouse testis differentiation.

Aard (alanine and arginine rich domain) is a gene of unknown function, previously reported to show sexually dimorphic expression in fetal mouse gonads. Here we describe the spatio-temporal expression profile of Aard during gonad development. The period of elevated mRNA expression coincides with early differentiation of the testis and is limited to Sertoli cells of the developing testis cords. Although low levels of Aard transcripts were detected in other tissues by quantitative RT-PCR assays, high levels of Aard expression is specific to the testis in both embryonic and adult mice.