Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats
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Date
2021
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Publisher
Elsevier Science
Abstract
Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant
release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor
2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5
inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic
candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adiponectin/
Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen
pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and
olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc)
and sildenafil (50.0 mg/kg; po) from gestational day 14–19. On gestational day 20, plasma and placenta homogenates
were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone
had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p <
0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to
gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin.
Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride,
total cholesterol, lactate, malondialdehyde and alanine aminotransferase were observed in testosterone-exposed
rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and
reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2.
Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome
which is accompanied by augmented placental adiponectin regardless of depressed Nrf2.
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Keywords
Adiponectin Poor fetal outcome Androgen Pregnancy Placental inefficiency
Citation
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