Study On The Effect Of Gold Nanoparticles In The Male Reproductive Toxicity And Male Contraception

Nanomaterials such as gold nanoparticles (AuNPs) are already being used in the fields of diagnostic imaging, drug delivery, and cancer photothermal therapy. In recent times, AuNPs have emerged as attractive candidates for delivery of various drug payloads to their targets. The increasing biomedical applications of AuNPs have raised major concerns regarding their in vivo fate and potential toxic effects in living organisms.Recently, AuNPs have been shown to induce oxidative stress and acute inflammation and cell apoptosis in the liver. The male reproductive system is known to be more sensitive to exogenous materials than other organ systems and has been classified as vulnerable in recent years. However, a great deal of additional information on the reproductive toxicity of gold nanoparticles, such as the distribution of AuNPs in reproductive organs and their ability to pass through reproduction-relevant physiological barriers [e.g. the blood-testis barrier (BTB)], are still unknown. We synthesize two surface-modified AuNPs, that is co-methoxy and ω-aminoethyl poly(ethylene glycol) capped AuNPs (mPEG@AuNP and PEG-NH2@AuNP). we intravenously injected mPEG@AuNP and PEG-NH2@AuNP and control (HEPES buffer, HBS) via the tail vein into adult male ICR mice. The accumulation of AuNPs in testes was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both mPEG@AuNP and PEG-NH2@AuNP can accumulate in the testes. The Au content of PEG-NH2@AuNP in testes was over two times higher than that of mPEG@AuNP at each time point. The dark field microscope images showed gold grains were located in the lumen of the seminiferous tubules, indicating that mPEG@AuNP can penetrate the BTB. By using TEM, we found that mPEG@AuNP was packed in vesicles of spermatogonia. Male ICR mice received three i.v injections of HBS, mPEG@AuNP and PEG-NH2@AuNP via the tail vein given every other day. We investigated the body weight, hormone levels, testes morphology, meiotic homologous chromosome synapsis and recombination. As well as, we mated the normal female mice with gold nanopartcles exposed male mice. The results showed there were no significant reproductive toxicity with gold nanoparticles treatment. However, we found male ICR mice received three i.v injections of PEG-NH2@AuNP, which elevated the testosterone levels of mice. The results indicated that PEG-NH2@AuNP might have a little toxicity. When we use the AuNPs, we should be care the surface modification of AuNPs.The results above showed AuNPs have no significant reproductive toxicity. The next plan is to investigate the application of AuNPs in male reproductive system. There are many reports showed that gold nanorods can absorp specific wavelength near infrared light (NIR) producing local hyperthermia. The studies used the photothermal effect of gold nanorods to cure tumors, which have obtained gold effect. Meanwhile, the sperm cells in male testes are temperature sensitive cells. There are some studies reported hot bath can kill the sperms, which were used in male contraception. We combined the two aspects studies, to reslove the contraception of stray animals with photothermal effect of gold nanorods. Firstly, we synthesized methoxy poly(ethyleneglycol)-modified gold nanorods (here abbreviated GNR), which can transfer the light energy of specific808nm infrared light (NIR) to hyperthermal energy. Secondly, we showed that in situ testicular injection of GNR in male mice, and we controlled the testes temperature by the dose of GNR and irradiation power of NIR. Finally, In a lower hyperthermia treatment, the morphology of testes and seminiferous tubules is only partly injured, and fertility indices are decreased to～10%at day7, then recovered to～50%at day60. In a higher hyperthermia treatment, the morphology of testes and seminiferous tubules are totally destroyed, and fertility indice sare decreased to0at day7, unrecovered forever. Herein, we have reported a less invasive and controllable procedure formale contraception. This method is more convenient, efficient,and cheaper than surgical castration, which can be chosen to treat the over population of pets and stray animals. The method is a significant basis for developing a new male contraception technology.