Investigation Of Female Reproductive Toxicity Induced By Multi-walled Carbon Nanotubes

The rapid development of chemistry and materials science produced a large number of new materials, in which nanomaterials represent the most striking example have entered into many aspects of people’s life. Nowadays, more and more people begin to concern the effects of nanomaterials on human health and ecological environment after intentional or unintentional exposure of nanoparticles. In2003, Science and Nature published articles one after another to explore the biological effects, environmental and healthy impacts cause by nanomaterials.Carbon nanotubes (CNTs) are collections of induvidual or several concentric graphite cylinders, and have attracted the attention of many scientists worldwide. CNTs represent the ideal, perfect and ordered carbon fiber. The size, structure, and topology make them possess unique electrical, magnetic, thermal and mechanical properties, and fascinating in plastics and composite materials, electronics, energy. The exploration in biomedicine is also rapidly developed into a new research field. However, the promise of the wide use of CNTs in biomedicine is their good compatibility and no toxic or side effects. The research in biological toxicity have found that CNTs can translocate in liver, spleen, kidney, and brain through blood circulation, and produce different degrees of damage. However, the study on female reproductive toxicity caused by CNTs is rare and need further study.The health of female reproduction shows a declining trend, due to various effects like industrial pollution. As an important part in safety evaluation of nanomaterials, it is imperative to understand the impact of nanomaterials on female reproductive system. Studies have been reported that gold nanopaticles and calcium phosphate nanoparticles can translocated into ovarian granulosa cell, and induced cell apoptosis and inhibited the secretion of estradiol. Prenatal exposure of single-walled carbon nanotubes caused fetal abnormalities such as morphology damage. Nevertheless, the effects of CNTs on female reproductiv system in non-pregnant period have not been investigated systematacially.CNTs have extensive prospect in manufacture and medicine, and have high risk of entering the human body actively or passively. Study the effects of CNTs on female reproductive health has a realistic significance. In view of the above considerations, we use ICR mouse as the mammalian model to investigate the effects of carboxylic multi-walled carbon nanotubes (MWCNT-COOH) on female reproductive system. According to the regulatory mechanism of the female reproductive system (hypothalamus-pituitary-ovarian axis), we investigated the distribution and effects of MWCNT-COOH on female reproductive organs, and further discussed the toxic mechanisms. The results showed that64Cu-labelled MWCNT-COOH can translocate in ovary, uterus and brain through tail vein injection and the accumulation showed a decreased trend within24h. Repeated administration of MWCNT-COOH prolonged the estrous cycle during the exposure time and inhibited the secretion of hormones (FSH, LH, estradiol, progesterone), which indicated that MWCNT-COOH disturbed the endocrine system of female mice. However, histologic studies of ovary and uterus showed little alteration after exposure. The number of corpus luteum and each stage follicles, thickness of the endometrium and myometrium from treated mice were characterized no difference compared with control mice. Fertility studies at day13and day60showed that MWCNT-COOH do not have detrimental effect on successful conception and healthy growth of offspring (litter size, survival rate, gain of body weight). To explore the mechanism of toxicity, we found that MWCNT-COOH increased the level of TNFa and changed the level of MDA and GSH in ovary and uterus. Further more, MWCNT-COOH do not possess estrogen-like activity because they are unable to maintain normal estrous cycle and cyclical change of uterus in ovariectomized mice.In conclusion, CNTs can translocate into the female reproductive organs and inhibite hormonal secretion, but leave the structure of organs and fertility not affected. CNTs do not possess estrogen-like effect in vivo, so their influence on endocrine system was not the antagonism effect with estrogen but may be the results of excessive reactive oxygen species caused on steroidogenic enzymes. Due to the complexity and importance of the female reproductive system, understanding of the impact of nanomaterials on reproductive health has a realistic significance. Our study has broadened the knowledge of nanotoxicology on female reproducive system and provided important experimental reference on safe application of carbon nanotubes in biological medicine.