Study of Reproductive Toxicological Effects of Gold Nanoparticles Following Superovulation With Rhfsh Eluting Chitosan Gold Nanosuspension in Female Rats

Abstract

In present study 49 female rats were divided equally (n=7) in seven groups i.e. 6 treatment and one control. Treatment groups were administered with different doses of rhFSH conjugated GNPs while control group were administered PBS. The rats were sacrificed (in diestrus phase) and ovaries and uterus were collected, thin sectioning (5 μ) was done and following H & E staining histopathological study was performed. The blood samples were collected and serum was separated to perform ELISA for estimation of Progesterone. There were no pathologies identified in the uterus of group 7 (control), 6 (administered 50.4 ng GNPs) and 3 (administered 63 ng GNPs). Group 2 (administered 75.6 ng GNPs) showed very mild degree of MNC infiltration and hyperaemia. Group 1 (administered 126 ng GNPs) showed very mild MNC infiltration, hyperaemia and hyperplasia. Group 5 (administered 138.6 ng GNPs) showed very mild degree of hyperplasia, MNC infiltration with moderate hyperaemia. Group 4 (administered 231 ng GNPs) showed very mild fibroplasia, epithelial degeneration, moderate hyperplasia and MNC infiltration with high degree hyperaemia. There were no noticeable pathologies seen in ovaries of groups 2, 3, 6 and 7 (control) while group 1 (administered 126 ng GNPs with 15 IU rhFSH) showed very mild MNC infiltration, follicular atresia, degeneration of corpus luteum and moderate degree of hyperaemia. Group 5 showed very mild MNC infiltration, follicular atreasia, follicular cyst and moderate degree of hyperaemia and degeneration of corpus luteum. Pathological changes recorded in group 4 were: very mild degeneration of granulosa cells and fibroplasia, moderate degree of hyperaemia, follicular atresia, follicular cyst, MNC infiltration and vacuolation in ovarian stromal cells with high degree degeneration of corpus luteum. P4 level was significantly higher in all the groups administered rhFSH conjugated GNPs to that of control group. Group 3 (7.5 IU rh FSH with 63 ng GNP) showed significantly high (P≤0.05) mean P4 levels (ng/ml) than group 6 (8.368 ± 0.324b vs 5.548 ± 0.264c, respectively) administered 6 IU rhFSH with 50.4 ng GNP. Group 2 administered further high dose of rhFSH (9 IU) with 75.6 ng GNP showed non-significant increase in mean P4 levels (ng) than group 3 (8.782 ± 0.171b vs 8.368 ± 0.324b, respectively). Further increment in the dose of rhFSH in Group 1 (administered 15 IU rhFSH with 126 ng GNP) showed significantly (P≤0.05) low mean P4 (7.440 ± 0.185a) than group 2 and 3. Further increment in doses to 16.5 IU rhFSH conjugated with 138.6 ng of GNP (group 5) mean P4 (6.292 ± 0.109d) further decreased significantly (P≤0.05). P4 levels in group 4 administered highest dose of rhFSH (27.5 IU, conjugated with 231 ng GNP) decreased significantly and reached to levels of mean P4 in group 6 (5.195 ± 0.330c Vs 5.548 ± 0.264c) administered lowest rhFSH suggesting that, degenerating effects of GNPs (at higher doses) lead to disruptive effects over steroidogenesis so rather administering higher dose of rhFSH (conjugated with high dose of GNPs) could not result in high levels of progesterone, rather, level of progesterone started decreasing following administration of high doses of GNPs.