pregnancy+and+ACE2
Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17β-oestradiol-dependent and sex chromosome-independent. 2010
E2 regulation of renal ACE2 has particular implications for women across their life span since this hormone changes radically during puberty, pregnancy and menopause.
Fetal Sex Affects Expression of Renin-Angiotensin
System Components in Term Human Decidua
Yu Wang, Kirsty G. Pringle, Shane D. Sykes, Francine Z. Marques,
Brian J. Morris, Tamas Zakar, and Eugenie R. Lumbers
School of Biomedical Sciences and Pharmacy (Y.W., K.G.P., S.D.S., E.R.L.), Mothers and Babies Research
Centre, and School of Medicine and Public Health (T.Z.), University of Newcastle, Hunter Medical
Research Institute and John Hunter Hospital, Newcastle, New South Wales 2300, Australia; and Basic &
Clinical Genomics Laboratory (F.Z.M., B.J.M.), School of Medical Sciences and Bosch Institute, University
of Sydney, Sydney, New South Wales 2006, Australia
The maternal decidua expresses the genes of the renin-angiotensin system (RAS). Human decidua
was collected at term either before labor (i.e. cesarean delivery) or after spontaneous labor. The
mRNA for prorenin (REN), prorenin receptor (ATP6AP2), angiotensinogen (AGT), angiotensin-
converting enzymes 1 and 2 (ACE1 and ACE2), angiotensin II type 1 receptor (AGTR1), and angio-
tensin 1–7 receptor (MAS1) were measured by quantitative real-time RT-PCR. Decidual explants
were cultured in duplicate for 24 and 48 h, and all RAS mRNA, and the secretion of prorenin,
angiotensin II, and angiotensin 1–7 was measured using quantitative real-time RT-PCR, ELISA, and
radioimmunoassay, respectively. In the decidua collected before labor, REN mRNA levels were
higher if the fetus was female. In addition, REN, ATP6AP2, AGT, and MAS1 mRNA abundance was
greater in decidual explants collected from women carrying a female fetus, as was prorenin pro-
tein. After 24 h, ACE1 mRNA was higher in the decidual explants from women with a male fetus,
whereas after 48 h, both ACE1 and ACE2 mRNA was higher in decidual explants from women with
a female fetus. Angiotensin II was present in all explants, but angiotensin 1–7 levels often regis-
tered below the lower limits of sensitivity for the assay. After labor, decidua, when compared with
nonlaboring decidua, demonstrated lower REN expression when the fetus was female. Therefore,
the maternal decidual RAS is regulated in a sex-specific manner, suggesting that it may function
differently when the fetus is male than when it is female. (Endocrinology 153: 462– 468, 2012)
