Abstract Introduction: Nano-silver (NS) particles have gained a great interest for their antimicrobial impacts in wound healing, surgical approaches and various medical fields. However, several reports showed NS-induced cytotoxic effects on different cell types in in-vivo and in-vitro studies. Angiogenesis plays an important role in follicular growth and degenerated ovarian vascularization leads to severe follicular atresia, which is able to enhance the macrophages infiltration. Thus, present study was aimed in order to clarify the pathways for NS-induced damages on ovarian tissue by evaluating the macrophages distribution as well as angiogenesis in NS-treated animals. Moreover, follicular growth was assessed by investigating atretic follicles number per ovary in mice model. Materials & methods: Twenty four mature female mice were divided into four groups of control-sham (received 2 mL of normal saline, orally), low dose NS-treated (0.5mg/kg, orally), medium dose NS-treated (1mg/kg, orally) and high dose NS-treated (5mg/kg, orally). After 35 days, the ovarian macrophages distribution and angiogenesis ratio were evaluated by using immunohisochemical and immunefluorescent staining for CD68 and FITC-conjugated CD31+, respectively. Total follicles and atretic follicles distribution on ovaries were investigated. Results: NS-treated animals showed significantly (P<0.05) decreased micro (<5μm) and macro (>5μm) vessels distribution in one mm2 of the tissue. This impairment elevated depending on dose. Reduced total follicular count, elevated follicular atresia associated with enhanced macrophage infiltration were revealed in NS-treated animals. Conclusions: We can suggest that NS exerts its impact by down-regulating the ovarian angiogenesis. Moreover, increased macrophages infiltration may attribute to impaired angiogenesis-induced hypoxia and increased follicular atresia.

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