The UV filter benzophenone 3 provokes loss of oocytes in rat ovary cultures

ABUD J; ZENCLUSSEN AC; SANTAMARÍA CG; MEYER N; RODRIGUEZ HA; PORPORATO M; KASS L

Mar del Plata

Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Benzophenone 3 (BP3) is frequently used as an organic UV filter insunscreens, as photoinitiator, indirect food additive, or fragrance enhancer.Given the increased use of sunscreens in the general population because of thegrowing concern about UV radiation and skin cancer, as well as the highprevalence of BP3 in water supplies, humans are highly exposed to BP3 by bothdermal and oral routes. Several in vitro and in vivo studies have evidenced theability of BP3 to act like an endocrine disrupting chemical. Our goal was tostudy the effect of BP3 in the follicular assembly and the potentialinvolvement of Foxl2 pathway using whole ovary cultures. Ovaries were collectedfrom Wistar rats at birth, treated in vitro with vehicle (0.01 % DMSO), BP3(5.8 nM and 876 nM) or ESR2 inhibitor (0.1 nM), and cultured for 7 days. Nestbreakdown, follicular assembly and the expression of several regulators ofthese processes (p27, Foxl2, Sox9, Bmp2, Cyp19 and Fst) were evaluated. Invitro exposure to BP3 (5.8 nM) decreased the population of total oocytes, thenumber of nests per ovary and early primary follicles population. In addition, BP3(5.8 nM) induced overexpression of Foxl2 mRNA levels through ERS2 but increasedFst mRNA levels independently from ERS2 or Foxl2. We also observed that thenumber of p27-positive oocytes was decreased after BP3. Taken together, ourresults show that exposure to BP3 (5.8 nM) perturb nest breakdown, causes adecrease of total oocytes reserve, and induces an overexpression of Foxl2 mRNAthrough ESR2. In conclusion, exposure to an environmentally relevant dose ofBP3 is enough to perturb the early events of germ cell development as showedhere in whole ovary cultures.