Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats
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Date
2021-06-14
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Publisher
Elsevier
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 adipo nectin/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.
Description
Keywords
Adiponectin, Poor fetal outcome, Androgen, Pregnancy, Placental inefficiency
Citation
Areola, E.D., Adewuyi, I.J., Usman, T.O., Tamunoibuomi, G., Arogundade, L.K., Olaoye, B., Matt-Ojo, D.D., Jeje, A.O., Oyabambi, A.O., Afolayan, E.A., & Olatunji, L.A. (2021). Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats. Toxicology Reports, 30 (8), 1358-1368, Published by Elsevier. Available online at: https://www.sciencedirect.com/journal/toxicology-reports/vol/8/suppl/C?page=2