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.

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

“…Similary, it was reported that BPA exposure altered chromosome and spindle organization which resulted in hyperploidy of mouse oocytes during meiosis (Can et al 2005) and it was also demonstrated that low BPA doses are related with aberration during meiotic prophase, including increased incidence of recombination (Susiarjo et al 2007) and failure formation of primordial follicle by inhibiting meiotic progression of oocytes . In contrast, Eichenlaub-Ritter and her colleagues found no evidence that low BPA doses increased hyperploidy at meiosis II.…”

An evaluation of evidence for the carcinogenic activity of bisphenol A

“…All doses increased the incidence of meiotic defects, with the highest dose causing chromosome misalignment in ∼11% of metaphase II-arrested oocytes, compared to ∼2% in controls. Exposure of isolated oocytes to BPA (10 μM or 2.3 μg/ml) in vitro induced a delay in cell cycle progression and disruption of spindle function due to interference with microtubule and centrosome dynamics [70]. Similar disturbances in microtubule dynamics have been observed in somatic cells in vitro.…”

“…Admittedly, most studies evaluating BPA-induced genetic alterations have involved in vitro assays, many of which have reported a lack of mutagenic activity [66][67][68]. However, some in vitro assays have reported genotoxic activity that correlates with morphological transformation [69] or aneuploidy in oocytes [70] and in vivo analyses have also indicated that BPA can induce aneuploidy in germ cells following embryonic exposure of C57BL/6 female mice to BPA via the maternal circulation beginning on 11.5 dpc [26;71].…”

TheCaenorhabditis elegans rsd-2andrsd-6Genes Are Required for Chromosome Functions During Exposure to Unfavorable Environments

“…Him phenotypes are also observed in mut-7 and rde-2 mutants (Ketting et al 1999) (Figure 4B), although this phenotype is observed at all temperatures in these strains. The fact that environmental factors can contribute to chromosome disjunction events is becoming increasingly appreciated (Can et al 2005). The dsRNA sensitivity of disjunction mechanisms in rsd-6 …”