P-654 Arsenic Exposure During Puberty Significantly Affected Sex Maturation and Reproductive System Development of Female SD Rats

Abstract Study question Can sex maturation and reproductive hormones affected by Arsenic exposure during puberty in female rats. Summary answer Pubertal AS exposure at environmental-relevant levels significantly enhanced sexual precocity but reduced reproductive functions and capacity by adult. What is known already Arsenic (AS) is widely distributed in the earth’s surface and its toxic effects have been known for a long time. About 130 million people, mainly in the developing countries, are overly exposed to the chemical of AS through the drinking water. AS contaminations in drinking water (10 - 50 ug/L) were associated with human reproductive defects, such as spontaneous abortion, stillbirth, lower birth weight, and smaller birth size. As exposures in adult rats were have been related to inhibition of steroidogenic enzymes and decreased estradiol levels. Study design, size, duration Forty female rats of 21 days of age were exposed to AS at different doses (0, 0.02, 0.2, or 2 mg/L, n = 10/group) through drinking water for about 44 days until the rats reached adulthood. In a second experiment, 24 rats were exposed to AS with a similar protocol and doses, in order to examine the effects of AS on the pregnancy and reproductive capacity. Participants/materials, setting, methods Sex maturation day and estrus cycles were recorded. When rats reached adult, serum pituitary and ovarian sex hormones were assayed. Ovarian steroidogenic pathway and its regulatory signaling molecules were analyzed by qPCR and/or Western blots. The parameters compared include Mating Index, Days with Copulatory Vaginal Sperm Plug, Pregnancy Rate, Fertility Index, Weight of Pups, Litter Size and Ratio of Male/Female Pups. Main results and the role of chance AS exposure significantly reduced the weights of both ovary and uterus without affecting the overall body weight. AS promoted sexual precocity, disturbed estrus cycles, significantly reduced the numbers of primordial follicles while increased atretic follicles. AS also reduced serum levels of estradiol, progesterone and testosterone but increased the LH and FSH levels in dose-dependent manners. In addition, AS selectively down-regulated steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK/JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, AS significantly reduced pup weights, litter size and the number of male pups. Limitations, reasons for caution Future works are need to examined how AS may affect the hypothalamic-pituitary functions during the prepubertal period. Further studies are required to address how AS may affect the environment of female reproductive tract and the egg qualities. Wider implications of the findings AS exposure at environmental-relevant level during puberty significantly affected female reproductive system development. Since the concentrations tested overlaps the environmental levels recorded, the results may have important public health significance. Trial registration number NA