The Assessment of Gadolinium Orthovanadate Nanoparticles Value for Neonatally-Induced Reproductive Disease in Male Rats

Abstract
The efficiency of gadolinium orthovanadate nanoparticles (NP GdVO4:Eu3+) in rats with neonatally-induced reproductive disease was investigated in order to develop a method for male hypofertility treatment. The offspring of intact rats received an excessive amount of phytoestrogens (Ph) with breast milk (1st group) from the 3rd to the 22nd day of age against the background of emotional stress ("Maternal separation stress"). At the age of 10 months, the males were fed with NP GdVO4:Eu3+ (0.33 mg/kg; the 2nd group) or reference drug speman (158 mg/kg; the 3rd group) for 70 days. Sexual behavior and fertility of males were examined; the integrated indicator of reproductive potential (Fi) was calculated relative to the rats of the control group which received vehicle (water). In the 1st group, sexual behavior of males was characterized by the acceleration of the copulation responses on a female (double shortening of mounting and intromission latency) and a reduced ability to achieve ejaculation and to start the second round of copulations. Those males inseminated less number of females (67% vs. 91% in control group), while almost all of them became pregnant. Neonatally-induced deterioration in the quality of male gametes resulted in high intrauterine pregnancy loss (more than twice), and the total fetal number decrease (by 21%). This fact determined a reduction of integrated indicator of reproductive potential (Fi) 2.6 times in males compared with that in control animals. Treating with NP GdVO4:Eu3+ restored male sexual behavior to the level in control group. The latter resulted in an increase in the number of fertilized females (up to 95%). In pregnant females, fetal losses decreased (up to 15.2% vs. 18.1% in the control group, p < 0.05), and the number of fetuses increased (by 25%, p < 0.05), showing an improvement in the quality of sperm. The integrated indicator of reproductive potential (Fi) increased to (8.3 ± 0.5) vs. (3.0 ± 0.3) cu. in the 1st group (without treatment), that statistically significant higher than that in control and the 3rd groups. Treating rats with neonatally-induced pathology of the reproductive function and metabolic disorders with NP GdVO4 normalizes sexual behavior, restores the quality of sperm and male fertility, and improves reproductive potential much more effectively than the reference drug speman does.