Systemic administration of 11β-HSD2 inhibitor results in PE-like
features in pregnant rats
Subcutaneous administration of CBX (0.6-2.4mg/kg) from GD7.5 to GD17.5
resulted in a decrease in 11β-HSD2
expression and activity in the
placentas (Fig.1A). The
significance was achieved in CBX (1.2 and 2.4 mg/kg) groups compared
with vehicle group. In contrast, 11β-HSD1 expression level in the
placentas was not significantly differed among vehicle and CBX groups
(supplemental Fig.S1). As expected, a significant increase in placental
corticosterone level was exhibited in CBX (1.2 and 2.4 mg/kg) groups
(Fig.1B). Maternal circulatory level of corticosterone was significantly
increased from GD 15.5 and reached the peak on GD 19.5 in the rats with
CBX (1.2 and 2.4 mg/kg) treatment (Fig.1C).
The pregnant rats with CBX treatment (1.2 and 2.4 mg/kg) displayed
PE-like features. As shown in Fig1D, MAP of these rats was significantly
elevated from GD 15.5 compared
with control rats. They also showed a significant increase in SBP
measured on GD 20.5 (Fig.1E). The protein/creatinine in urine was also
elevated in the rats with CBX treatment (1.2 and 2.4 mg/kg) (Fig.1F).
Histology analysis of kidney showed mesangial hypercellularity and
occlusion of capillary loops and the urinary space in the glomeruli
(Fig.1G)
and a higher histopathological score in CBX groups compared with vehicle
group (Fig.1H). IUGR was found in CBX (1.2 and 2.4 mg/kg) groups as
evidenced by decreased fetal weight (Fig.1I). Moreover, a significant
increase in circulatory sFlt1 level and sFlt1/ PlGF ratio occurred in
CBX (1.2 and 2.4 mg/kg) groups
(Fig.1J),
but circulatory PlGF and VEGF levels were not significantly changed in
these animals (supplemental Fig.S2).