Regulation of the Renin—Angiotensin System Pathways in the Human Decidua

Abstract

Pregnancy outcome is influenced, in part, by the sex of the fetus. Decidual renin messenger RNA (REN) abundance is greater in women carrying a female fetus than a male fetus. Here, we explore whether the sex of the fetus also influences the regulation of decidual RAS expression with a known stimulator of renal renin and cyclic adenosine monophosphate (cAMP). Cyclic adenosine monophosphate had no affect on decidual REN expression, since REN abundance was still greater in decidual explants from women carrying a female fetus than a male fetus after cAMP treatment. Cyclic adenosine monophosphate decreased prorenin levels in the supernatant if the fetus was female (ie, prorenin levels were no longer sexually dimorphic) and altered the fetal sex-specific differences in other RAS genes seen in vitro. Therefore, fetal sex influences the decidual renin-angiotensin system response to cAMP. This may be related to the presence of fetal cells in the maternal decidua.

The intrauterine renin–angiotensin system: Sex‐specific effects on the prevalence of spontaneous preterm birth

“…These same processes may also be at play in the decidua. As described above there is a reduced level of expression of the ACE2/Ang‐(1‐7)/MasR pathway in decidua from women with male fetuses . We postulate that this reduction in activity of the RAS anti‐inflammatory pathway makes pregnancies carrying male fetuses more vulnerable to inflammation, so putting them at greater risk of preterm birth.…”

“…All components of the RAS have been identified in term human decidua, placenta, myometrium, and fetal membranes [22][23][24] and it has been demonstrated that the decidua is the major source of prorenin protein within the human uterus. 25,26 That is, there is a low level of expression of prorenin mRNA (REN) in amnion and chorion, but amnion and chorion, like decidua, contain high levels of prorenin protein. 27,28 The low level of expression of amnion REN mRNA in the presence of very high levels of prorenin protein suggests that prorenin secreted from the decidua diffuses into the fetal membranes.…”

“…As described above there is a reduced level of expression of the ACE2/Ang-(1-7)/MasR pathway in decidua from women with male fetuses. 26 We postulate that this reduction in activity of the RAS antiinflammatory pathway makes pregnancies carrying male fetuses more vulnerable to inflammation, so putting them at greater risk of preterm birth. Interestingly women delivering preterm have lower Ang- (1)(2)(3)(4)(5)(6)(7) and lower Ang-(1-7)/Ang II ratios in their plasma compared with levels in women delivering at term.…”

The AT1/Raf/ERK1/2 signaling pathway is involved in Angiotensin II-enhanced proliferation of hepatic carcinoma cells

“…Angiogenesis is one of the most critical steps in hepatic carcinoma progression [8][9][10]. Recent studies have revealed that the renin-angiotensin system (RAS), which regulates a diversity of physiological functions including blood pressure, fluid balance and placental development [11][12][13], is involved in the regulation of angiogenesis and may have an important role in the progression of hepatic carcinoma [14,15]. Angiotensin (Ang) II is the major biologically active effector generated by the RAS system in vasculature, and increasing evidence has shown that Ang II facilitates cancer cell behavior in various human malignancies through cell proliferation, migration and metastasis.…”

“…Ang II acts through two different transmembrane receptors in the G protein-coupled receptor family: Ang II type 1 (AT1) and type 2 (AT2) [20]. It has been reported that Ang II stimulates vasoconstriction, aldosterone production, angiogenesis and cell proliferation by the AT1 receptor and produces the opposite effects via the AT2 receptor [12,21,22]. It is well known that the AT1 receptor mediates most of the physiological and pathological functions of Ang II by interacting with various G proteins, producing second messengers and also activating multiple intracellular protein kinases [23].…”