ADVEH.SE EFFECTS OF ARSENIC EXPOSURE ON !{EPRODUCTIVE FUNCTION OF FEMALE RAT

Abstract

The purpose of the present investigation was to examine the adverse effects of arsenic on function and structure of reproductive organs in the female rat at 56 days of age, after exposed to different doses (50ppm, 100ppm, and 200ppm) of sodium arsenite at immature/growing age (28days) for 28 days. General body health, physical activity and body weight of rats was reduced with arsenite treatments in a dose dependent malmer compared to control. The highest decrease in physical activity, general health and body weight (P<O.OOl) was observed in high dose groups (100ppm, 200ppm) throughout the experiment, and was more prominent in 200ppm of arsenite. Dose dependent decrease was observed in mean ovarian, oviduct and uterine weight and length compared to control. Highest (P<O.OOI) reductions in organ weight were observed in high dose groups (100ppm, 200ppm) even compared to the low dose group (50ppm). Folliculogenesis was disturbed in a dose-dependent malmer. A prominent increase (P<O.OI) in mean number of primary follicles was observed in high dose groups (100ppm, 200ppm). However, the number of developing follicles, small and medium graffian follicles decreased in all the doses and more (P<O.Ol) reduction was observed in the high dose (200ppm) group compared to control. Large graffian follicles were not found in the high dose groups (100ppm, 200ppm). More number of atretic follicles was observed in high dose groups. Some abnormal primary follicles with disruted oocyte and invisible nucleus were observed in high dose groups. In some graffian follicles of high dose groups no corona radiata and cLUmllus oophorus were observed, rather the oocyte laid directly on the peripheral granulosa layer. Loosening in cells of granulosa and theca layer was observed in graffian follicles of the 100ppm and 200ppm groups. Lesser numbers of corpora lutea were also seen in high dose groups, compared to control. Mean diameters of primary follicles, developing follicles, graffian follicles and thickness of peripheral granulosa layer of graffian follicles were reduced in a dosedependent manner. The greatest reduction was observed in diameters of all categories of deVeloping follicles, small graffian and medium graffian follicles in 200ppm of arsenite compared to the control group. DNA damage in ovarian cells was measured by comet assay. In all the treatmcnt groups, the mean number of cells with intact DNA decreased, while comet numbers increased significalltly (P<O.OO 1) in a dose-dependent manner compared to the control. Percent DNA in the comet head decreased, while comet number, comet length, comet height, comet head diameter, comet tail length, %DNA in comet tail, tail moment and olive moment increased significantly in high dose groups compared to control and low dose group. Histomorphology of isthmic and ampullary regions of the oviduct was disturbed by arsenite treatment. Loosening and disorganized cellular arrangement was observed in muscular layer and epithelium of high dose groups (100ppm, 200ppm) along with low expression of cilia against increased doses of arsenite. Negligible cilia were observed in istlmlic epithelium of the 200ppm group. Mean thickness of the muscular layer and epithelial height of ampulla and istlunus were reduced significantly (P<O. 00 1) in a dose-dependent manner compared to the control. XlV Abstract Uterine epithelium in low dose group (50ppm) was lined by cuboidal shaped cells instead of columnar cells with basal elongated nuclei observed in control epithelium. In high dose groups (100ppm, 200ppm) no demarcation was observed between epithelial cells and endometrial stroma. No basement membrane was seen in high dose groups, even in low dose group, basement membrane was disturbed. The endometrial stroma in high dose groups was very dense in appearance. In myometrium, loosening of cells was profound in high dose groups. Mean uterinc diameter, epithelial height, thickness of endometrium and myometrium were reduced significantly (P<O.OOl) in a dose-dependent manner compared to control. In all the treatment groups, plasma levels of estradiol, progesterone, FSH and LH were decreased significantly (P<O.OOl) in a dose-dependent manner compared to control. Greatest reduction was observed in high dose groups (100ppm, 200ppm) even compared to low dose group. High arsenic deposition was found in blood, ovary, oviduct and uterine tissue in all the treatment groups compared to the control, which was more profound in high dose group (200ppm) even, compared to other treatment groups. In summary, it is concluded from the present study, that sodium arsenite treatment gi yen to immature rats (28 days age), adversely affect their reproductive function and structure in a dose-dependent manner when they become mature (56 days age). Reduced body weight, changes in organ weight, disturbed folliculogenesis, restricted ['unction of oviduct and uterus, disorganized cellular structure, DNA damage in ovarian cells, altered gonadotrophins and steroid levels, all are the major factors responsible for infertility. Present investigation indicates arsenic as a reproductive toxicant and as an endo crine disruptor. Arsenic, a major threat to female of young age not only at high dose level, but also at lower concentration, it harms the general body health as well as the reproductive health of female.