Fetal Sex Affects Expression of Renin-Angiotensin System Components in Term Human Decidua

Wang, Yu; Pringle, Kirsty G.; Sykes, Shane D.; Marques, Francine Z.; Morris, Brian J.; Zakár, Tamás; Lumbers, Eugenie R.

doi:10.1210/en.2011-1316

Cited by 46 publications

(54 citation statements)

References 33 publications

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“…These findings are consistent with the observation that (P)RR mRNA abundance is greater in decidual explants collected from women carrying a female fetus (34).…”

Section: Articlessupporting

confidence: 92%

Ontogeny of the (pro)renin receptor

2013

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Background: This study examined temporal expression of the (pro)renin receptor ((P)RR), during renal, heart, lung, and brain organogenesis in the mouse. Methods: (P)RR expression was determined by quantitative reverse-transcription PCR, western blotting, and immunohistochemistry. results: Brain, kidney, and lung (P)RR mRNA levels increased progressively during gestation and peak on postnatal day (P)10. (P)RR protein contents were high during gestation in all organs studied and declined with maturation. Brain (P)RR was expressed most prominently in the ependymal lining of the ventricles. In the embryonic day (E)16.5 and E18.5 metanephros, (P)RR was present in the ureteric bud and ureteric bud-derived collecting ducts. In the fetal heart, (P)RR was expressed diffusely in the myocardium, whereas pulmonary (P) RR was detected at highest levels in the epithelium of branching airways. Treatment of newborn kidneys with the angiotensin (Ang) II type 1 receptor (AT 1 R) antagonist candesartan increased (P)RR mRNA levels. conclusion: (P)RR gene and protein expressions in the brain, kidney, heart, and lung are developmentally regulated in a tissue-specific manner. Endogenous Ang II, acting via the AT 1 R, exerts a negative feedback on (P)RR in the newborn kidney. These findings suggest that high (P)RR protein levels observed during gestation may play a role in brain, kidney, heart, and lung organogenesis.

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“…These findings are consistent with the observation that (P)RR mRNA abundance is greater in decidual explants collected from women carrying a female fetus (34).…”

Section: Articlessupporting

confidence: 92%

Ontogeny of the (pro)renin receptor

2013

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“…13 These findings suggest that fetal and utero-placental components, including the placenta, may be major sources of s(P)RR in pregnant women and that plasma s(P)RR concentrations may increase with fetal and placental growth. Furthermore, although the components of the RAS in intrauterine tissues are reportedly altered by fetal sex during pregnancy, 20 plasma s(P)RR concentrations at each gestational period did not vary significantly between women carrying a male versus a female fetus (early pregnancy, 28.9 ± 7.6 versus 30.6 ± 12.0, P=0.076; mid-pregnancy, 30.8 ± 9.5 versus 31.8 ± 13.9, P=0.44; late pregnancy, 38.9 ± 8.0 versus 39.4 ± 9.6, P=0.56; and at delivery, 39.9 ± 10.3 versus 41.0 ± 10.6, P=0.32).…”

Section: Discussionmentioning

confidence: 99%

“…The function of the tissue RAS in pregnancy, however, has not been fully elucidated, although previous reports suggest a critical role played by the tissue RAS in feto-placental circulation, as well as trophoblast Abstract-The renin-angiotensin system is believed to influence blood pressure (BP) during pregnancy, but the associations between BP during pregnancy and the soluble form of the (pro)renin receptor (s[P]RR), a new component of the tissue renin-angiotensin system, remain undetermined. In this prospective cohort study of 437 pregnant women with normal BP (systolic <140 mm Hg and diastolic <90 mm Hg) during early pregnancy (<16 weeks of gestation) regression analysis was performed to examine the associations between plasma s(P)RR concentrations and BP in 3 gestational stages (20)(21)(22)(23)(24)(28)(29)(30)(31)(32), and 36-40 weeks of gestation) and logistic regression analysis to evaluate the incidence of preeclampsia. Plasma s(P)RR concentrations at early, middle (16- invasion and migration.…”

mentioning

confidence: 99%

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

et al. 2012

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http://hyper.ahajournals.org/ Downloaded from Watanabe et al S(P)RR During Pregnancy 1251invasion and migration. 16,17 Clinically during pregnancy, it is well-known that even women with no complication exhibit BP changes with gestational age; the BP is typically at its lowest between 24 and 26 gestational weeks, increasing thereafter until the end of the pregnancy. 18 In addition, the circulating RAS is involved in the development of hypertensive disorders, including preeclampsia, during pregnancy. 1,16,19 However, no evidence suggests that the tissue RAS contributes to BP changes during pregnancy.On the basis of these background findings, the present study was conducted to examine whether the tissue RAS contributed to BP changes during pregnancy and the incidence of preeclampsia. To this end, we assessed the relationship between plasma s(P)RR concentrations and BP levels during pregnancy in a prospective cohort study. Methods Study ParticipantsIn this prospective cohort study, Japanese pregnant women whose first visit to the National Center for Child Health and Development hospital was at <16 weeks and 0 days of gestation were enrolled between January and December 2010. At recruitment, written informed consent was obtained from all participants. The study protocol was approved by the ethics committee of the National Center for Child Health and Development (Tokyo, Japan).The expected due date was confirmed by ultrasound in all participants. Inclusion criteria were systolic BP <140 mm Hg and diastolic BP <90 mm Hg at the time of enrollment (<16 weeks of gestation) and the absence of preexisting hypertensive disorders and renal disease. The study initially enrolled 477 pregnant women who met the criteria; however, 40 pregnant women were excluded because of early abortion (n=8) or the inability to follow-up because of relocation (n=32), resulting in a total of 437 study participants.Plasma samples were obtained at 3 prenatal visits throughout the pregnancy and at time of delivery. The first sample was obtained before 16 weeks 0 days gestation (early pregnancy), the second between 16 weeks 0 days and 27 weeks 6 days gestation (mid-pregnancy), and the third after 28 weeks 0 days gestation (late pregnancy) at routine blood testing during prenatal visits. The fourth blood sample was obtained at time of delivery. We determined s(P)RR concentrations for first, second, and third trimester using the blood samples obtained in early, middle, and late pregnancy, respectively. We then analyzed s(P) RR concentrations in early pregnancy in association with BP values measured at 16 to 20, 20 to 24, 24 to 28, 28 to 32, 32 to 36, and 36 to 40 weeks of gestation (6 periods). Similarly, s(P)RR concentrations in mid-pregnancy were analyzed in association with BP levels measured at 28 to 32, 32 to 36, and 36 to 40 weeks gestation (3 periods) and s(P)RR concentrations in late pregnancy with BP levels measured at 36 to 40 weeks gestation (1 period). Finally, s(P)RR at delivery was used for analysis of the association between s(P)RR conce...

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“…13 Decidual REN expression was low both before and after labor in pregnancies where the fetus was male. 13 There were no other effects of sex or labor on decidual RAS expression, that is, there were no effects on angiotensinogen (AGT), PRR (ATP6AP2), ACE (ACE), ACE2 (ACE2), AT 1 R (AGTR1), and AT 2 R (AGTR2) gene expression. 11,13 Surprisingly, when isolated decidua was cultured ex vivo, decidual REN mRNA and prorenin protein levels remained high in pregnancies where the fetus was female, that is, this fetal sex-specific effect on gene expression was maintained for up to 48 hours ex vivo in decidual explant cultures and corresponded to high levels of prorenin in the supernatants of these explants.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2015

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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.

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Fetal Sex Affects Expression of Renin-Angiotensin System Components in Term Human Decidua

Cited by 46 publications

References 33 publications

Ontogeny of the (pro)renin receptor

Ontogeny of the (pro)renin receptor

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

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

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