Effect of the Ethanolic Extract of Salvia officinalis on Ovarian Angiogenesis in Mice at Preimplantation: A Morphological and Molecular Analysis

[Background]Salvia officinalis is a phytoestrogen, which is used to reduce clinical signs of pregnancy and improve the female infertility in herbal medicine treatment. The effect of S. officinalis on ovarian angiogenesis at the preimplantation time is unknown.[Objectives]This research was a histomorphometric and quantitative real-time study on angiogenic activity in the ovarian tissue in mice after exposure to S. officinalis at preimplantaion.[Methods]The extract of S. officinalis leaves, which was analyzed by phytochemical methods, administered at a dose of 100 mg/kg daily for 14 days to female mice. Then, pseudopregnancy was induced and ovarian tissue samples were removed for histological and molecular assessment.[Results]Data analysis on the space-solid phase micro extraction/gas chromatography-mass spectrometry demonstrated α-thujone (33.90%), camphor (19.34%), cineole (11.01%) and ß-thujone (9.48%) were the dominating compounds in the leaves of S. officinalis. Data analysis on histomorphometric parameters showed a significant difference in the vascular parameters between the test and control groups. Furthermore, gene expression analysis implied an increased level of the vascular endothelial growth factor (VEGF) (3.175) and was also associated with an increase in the level of Kinase insert domain protein receptor (KDR/Flk) gene expression (3.556) and FMS-like tyrosine kinase (Flt) gene expression (3.437) in the test group compared to the control group.[Conclusions]Increased ovarian angiogenesis after exposure to S. officinalis may induce vascular permeability and finally contribute to a variety of disorders including clinical signs similar to the ovarian hyperstimulation syndrome.