Bisphenol-A induces cell cycle delay and alters centrosome and spindle microtubular organization in oocytes during meiosis

Abstract

Bisphenol-A (BPA) is a widely used environmental estrogen-like chemical that has a weak estrogenic activity. This study aimed to test the potential inhibitory effects of BPA on meiotic cell cycle progression, centrosomes and spindle integrity in mouse cumulus-oocyte complexes (COCs). They were exposed to BPA (10-30 microM; 2.3-6.8 ppm) during meiosis-I and the formation of metaphase-II (M-II) spindle. Exposure to BPA during meiosis-I caused a dose-dependent retardation/inhibition of cell cycle progression; 74 and 61% of cells reached metaphase-I (M-I) in the presence of 10 and 30 microM BPA, respectively, (81% in controls, P<0.001). A more striking delay was noted when oocytes were exposed to BPA during the formation of M-II spindle, i.e. 61 and 41% of cells (94% in controls, P<0.001) reached M-II while the remaining cells remained at M-I. Depending on dose, both (i) loosening and elongation of meiotic spindles and (ii) compaction and dispersion of pericentriolar material (PCM) were noted in all samples, all of which resulted in a series of spindle abnormalities. Interestingly, no chromosome was detected in the first polar body after the 10 and 30 microM BPA treatments. When the cells were freed from BPA exposure at 10 and 30 microM, 70 and 61%, of the cells succeeded in reaching M-II (93% in controls, P<0.001), respectively. In conclusion, one mode of action of BPA is a moderately severe yet reversible delay in the meiotic cell cycle, possibly by a mechanism that degrades centrosomal proteins and thus perturbs the spindle microtubule organization and chromosome segregation.