Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats

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dc.contributor.authorEmmanuel Damilare Areola, Ifeoluwa Jesufemi Adewuyi, Taofeek Olumayowa Usman, God’sgift Tamunoibuomi, Lucy Kemi Arogundade, Barakat Olaoye, Deborah Damilayo Matt-Ojo, Abdulrazaq Olatunji Jeje, Adewumi Oluwafemi Oyabambi, Enoch Abiodun Afolayan, Lawrence Aderemi Olatunji
dc.date.accessioned2026-04-18T17:26:36Z
dc.date.available2026-04-18T17:26:36Z
dc.date.issued2021
dc.description.abstractTestosterone 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.
dc.identifier.citation2
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/123456789/17351
dc.language.isoen
dc.publisherElsevier Science
dc.subjectAdiponectin Poor fetal outcome Androgen Pregnancy Placental inefficiency
dc.titleSildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats
dc.typeArticle

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