Benzophenone-3 (BP-3) is an ultraviolet radiation filter used in sunscreens and as a fragrance enhancer. The phenolic compound has estrogenic activity in both in vitro and in vivo assays. Benzophenone-3 is rapidly metabolized by the liver into three major metabolites, benzophenone-1 (BP-1) being one of them. Benzophenone-1 has greater estrogenic activity than BP-3 and is weakly anti-androgenic, inhibiting testosterone activity. Estrogen and estrogenic compounds such as BP-3 are known to inhibit the process of ovarian primordial follicle formation in mammals. The oocytes in primordial follicles represent the entire germ cell availability for the female’s lifespan. Primordial follicle formation occurs during fetal development or early in neonatal life. We evaluated the effect of BP-1 on ovarian follicle formation. We used a neonatal ovary culture system to test the hypothesis that follicle formation is inhibited or delayed by BP-1. Ovaries from newborn female rats were cultured in the presence of BP-1 (5 or 50 ng/mL) or vehicle for four days. During the culture period, cysts break down and primordial follicles form. The extent to which this process occurs was quantified by counting the oocytes that have formed follicles and those that have not in histological sections. Each of the means for the number of cysts, number in cysts, primordial follicles, and primary follicles in each of the doses of 5 ng/mL and 50 ng/mL were compared to the control (0 ng/mL) using One-way ANOVA and Dunnett’s post hoc test. Mean comparison with number of cysts showed no significant difference with either dose of 5 ng/mL (p = 0.2589) or 50 ng/mL (p = 0.0860). No significant difference was found between a dose of 5 ng/mL (p = 0.7840) and control when comparing the mean number in cysts per ovary. However, there was a significant difference when comparing the control to a dose of 50 ng/mL. Between the control and the 50 ng/mL dose, there was a decrease in both the number of oocytes in cysts (p = 0.0391) and primordial follicles (p = 0.0070). There was no effect on the number of primary follicles at either 5 ng/mL (p = 0.5379) or 50 ng/mL (p = 0.4151). It is likely that BP-1 kills oocytes rather than inhibit follicle formation in the neonatal ovary. This is the first investigation of the impact of BP-1 on ovarian development and is important because, through routine human exposure to BP-3 in sunscreen products, the ovary is more likely to be exposed to the more potently estrogenic BP-1 rather than the parent compound BP-3.
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