Chronic treatment with Sildenafil has no effect on folliculogenesis or fertility in C57BL/6 and C57BL/6 knockout for iNOS mice

Tissue Cell. 2015 Oct;47(5):515-25. doi: 10.1016/j.tice.2015.07.001. Epub 2015 Jul 4.

Abstract

Sildenafil is an important phosphodiesterase inhibitor used to treat a range of diseases, including cardiovascular disease, prostatic hyperplasia and pulmonary hypertension. Its main mechanism of action is the inhibition of phosphodiesterase 5, leading to increased intracellular cyclic guanosine 3',5'-monophosphate. This second messenger plays an interesting role in the reproductive tract. The aim of the present study was to evaluate the effect of Sildenafil on folliculogenesis and fertility in mice. To do so, C57BL/6 wild-type mice and inducible nitric oxide synthase knockout (iNOS(-/-)) mice were treated with Sildenafil, and reproductive variables were evaluated. The treated and control animals underwent estrous cycle and fertility assay. Lipid profile, serum nitric oxide levels and the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and guanylate cyclase were evaluated. Additionally, ovaries were submitted to histological and morphological analysis. The findings demonstrated that chronic treatment with Sildenafil had no effect on folliculogenesis or fertility in C57BL/6 mice, suggesting that this drug can be safely used by women of childbearing age.

Keywords: Ovary; PDE5; Sildenafil.

MeSH terms

  • Animals
  • Estrous Cycle / drug effects
  • Estrous Cycle / physiology
  • Fertility / drug effects*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / drug effects*
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / drug effects*
  • Sildenafil Citrate / administration & dosage
  • Sildenafil Citrate / pharmacology*

Substances

  • Nitric Oxide
  • Sildenafil Citrate
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III