[The role of hypothalamus polycomb gene methylation in bisphenol A exposure during pregnancy and premature puberty in female offspring].

To explore the role of hypothalamus Polycomb Group (PcG) gene () methylation in the relationship between bisphenol A (BPA) exposure during pregnancy and premature puberty in female offspring. A total of 40 pregnant CD-1 mice were randomly and averagely assigned into four groups: control group (corn oil) and low, middle and high BPA-exposed groups (the poisonous doses were 8 mg/kg, 40 mg/kg, and 200 mg/kg, respectively) by random number table method. Each group was administered by gavage from gestational day (GD) 1 to 18. The vaginal opening of female offspring was observed from postnatal day (PND) 21 to 33. All female offsprings were sacrificed, and hypothalamus was remained on the PND 34. The methylation levels of and in the hypothalamus were measured. The early puberty of CD-1 mice was evaluated by the rate of vaginal opening in advance, initial time of vaginal opening, the first estrus occurrence and vaginal opening days in advance. The path model was used to explore the role of and gene methylation in the early puberty of female offspring with maternal BPA exposed including the number of days of vaginal opening in advance as a dependent variable and BPA exposure as an independent variable. The rate of vaginal opening on the 28 day in each maternal BPA-exposure group [low, middle and high BPA-exposed groups were 40.00% (29/72), 47.62% (25/53) and 37.84% (20/53), respectively] was higher than that rate in the control group [14.06%(9/64)]. Similarly, the (50)((25), (75)) values of initial time of vaginal opening in low, middle and high BPA-exposed group were 28 (26, 30), 28 (26, 29), 28 (26, 30) days, respectively and the (50)((25), (75)) values of the first estrus occurrence in low, middle and high BPA-exposed group were 31 (27, 32), 30 (27, 31), 31 (28, 33) days, respectively, which were earlier than those in the control group [initial time of vaginal opening was 30(28, 31) days, and the first estrus occurrence was 32(30, 33) days] (all values<0.05). Compared with the control group (the methylation levels of 1, 2, 2 were 1.47%, 1.26%, 2.56%, respectively), the methylation levels of 1 (1.61%-1.82%), 2 (1.36%-1.43%) and 2 (2.87%-3.05%) in female offspring were significantly higher in BPA-exposed groups (all values<0.05). The results of path model analysis showed that BPA had no direct influence on puberty in advance, but had an indirect effect on puberty in advance (indirect effect path coefficient was 0.045 and 0.142, respectively) by mediating methylation of 2, and 2. Early puberty in female offspring induced by maternal exposure to BPA during pregnancy through the increased methylation levels of hypothalamus PcG gene (, ) in female offspring.