Is sildenafil citrate affect endometrial receptivity? an immunohistochemical study

Abstract

The authors aimed to investigate the effect of sildenafil citrate (Sc) on expressions of β(3) integrin and vascular endothelial growth factor (VEGF), which is taking part in endometrium receptivity in implantation window period in controlled ovarian hyperstimulation (COH) performed rats. In this study, Wistar albino female rats were used and were divided into four groups as control, COH, Sc, and COH + Sc groups. They were sacrificed on the third, fourth, and fifth day of pregnancy, uteruses were resected, and uteri sections were stained with immunohistochemical method and evaluated. β(3) integrin immunoreactivity was most intensely observed in the endometrial glandular epithelium (GE) and stromal cells in the Sc group on the third day, whereas immunoreactivity was most intensely detected in the luminal epithelium (LE), GE, and stromal cells in the Sc group on the fourth day. VEGF immunoreactivity was most intensely observed in the endometrial LE in the Sc group on the third day, in the Sc and COH + Sc groups on the fourth day, and in the COH + Sc group on the fifth day. Our results indicated that Sc plays a role in both implantation and decidualization by affecting β(3) integrin and VEGF expressions in implantation window period in rats.

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

“…Sildenafil has been shown in animal studies to significantly reduce elevated sFLT1 and sENG, increase free VEGF, and reverse oxidative stress (51)(52)(53). Sildenafil treatment in pre-eclamptic rat studies has lowered blood pressure, reduced proteinuria, and enhanced placental perfusion (52).…”

Sildenafil citrate adjuvant treatment in women with polycystic ovary syndrome following clomiphene failure: A randomized controlled trial

“…Sildenafil citrate was shown to have selective endometrial vasodilatory action in women with Asherman syndrome [26] and improves endometrial development in women with thin endometrium by increasing radial artery flow [27] . In addition, animal studies showed that sildenafil citrate modulates endometrial receptivity by affecting endometrial VEGF and β3 integrin expression during implantation window [28] . Moreover, sildenafil citrate was shown to have an immunomodulatory effect on the peri-implantation endometrial microenvironment by inhibiting NK-cell activity [29] .…”

“…Sildenafil citrate is a phosphodiesterase-5 inhibitor that enhances subendometrial blood flow by potentiating the vasodilatory effect of nitric oxide [6] . It was reported to improve uterine blood flow, enhance endometrial development [7][8][9][10] and modulate endometrial receptivity [11] . Thus, it was used with varying success in the setting of repeated IVF failure with poor endometrial development [8] and to lesser extent in the setting of clomiphene citrateinduced thin endometrium [12,13] .…”

Non-classical effects of sildenafil in clinical medicine: an interdisciplinary approach

“…Имеются также клинико-экспериментальные доказательства эффективности и безопасности применения силденафила при лечении репродуктивных нарушений у женщин (синдром «тонкого эндометрия»), воспалительных гинекологических заболеваний и их последствий [91][92][93], а также женских сексуальных дисфункций, в т. ч. медикаментозно-индуцированного генеза [94][95].…”