菟丝子黄酮缓解妊娠期双酚A暴露对子代成年雌鼠的生殖损伤作用

Cuscuta chinensis flavonoids attenuate reproductive damage of offspring adult female mice exposed to bisphenol A during pregnancy

为探究菟丝子黄酮(CCFs)对母鼠妊娠期暴露双酚A(BPA)导致的子代成年雌鼠生殖损伤的缓解作用,将50只妊娠母鼠随机分为5组,即空白对照组、BPA模型组、BPA+低剂量CCFs组、BPA+中剂量CCFs组、BPA+高剂量CCFs组,每组10只,分别在孕1~17 d灌胃0.2 mL含有相应剂量药物的玉米油。待仔鼠出生56日龄时,每组随机选取10只子代成年雌鼠,收集血液和卵巢,统计各组成年雌鼠的卵巢指数;检测各组子代成年雌鼠血清中促性腺激素释放激素(GnRH)、卵泡刺激素(FSH)、黄体生成素(LH)的含量;检测每组卵巢组织中雌激素(E2)、孕酮(P4)、雌激素受体α(ERα)、雌激素受体β(ERβ)水平;检测卵巢组织活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)活性;HE染色观察各组卵巢组织学改变;荧光定量PCR法检测卵巢组织Nrf2、NQO1、HO-1 mRNA的表达。结果显示,BPA模型组小鼠卵巢指数升高,GnRH、FSH、LH、E2和P4激素水平降低,卵巢组织中ER水平紊乱。BPA对小鼠激素水平的影响可能是通过氧化应激造成的,卵巢组织SOD含量降低,ROS和MDA含量上升,同时,卵巢中HO-1、Nrf2、NQO1 mRNA的表达水平下调。但不同剂量的CCFs可保护雌鼠卵巢功能,下调卵巢指数、激素水平和氧化应激指标与BPA组小鼠趋势相反。研究表明,菟丝子黄酮对母鼠妊娠期BPA暴露引起的生殖损伤有一定的缓解作用,尤其是高剂量菟丝子黄酮的缓解效果相对显著。

In order to explore the alleviating effect of Cuscuta chinensis flavonoids(CCFs)on the reproductive damage of offspring adult female mice exposed to BPA during pregnancy,50 pregnant female mice were randomly divided into 5 groups,namely control group,BPA group,BPA+lowdose CCFs group,BPA+medium-dose CCFs group,and BPA+high-dose CCFs group,with 10 rats in each group,and were respectively gavaged on d 1-17 of pregnancy with 0.2 mL of corn oil containing corresponding doses of drugs.When the pups were 56 days old after birth,10 offspring adult female mice were randomly selected from each group,blood and ovaries were collected,and the ovarian index of the adult female mice in each group was counted;the levels of gonadotropinreleasing hormone(GnRH)and follicle-stimulating hormone in the serum and ovarian tissues of adult female mice in each group were detected.Levels of FSH,luteinizing hormone(LH),estrogen(E_2),progesterone(P_4),estrogen receptor alpha(ERα),estrogen receptor beta(ERβ),ovarian tissue reactive oxygen species(ROS),superoxide dismutase(SOD),and malondialdehyde(MDA)activities were determined.HE staining was used to observe the pathological changes of ovarian tissue in each group;fluorescent quantitative PCR was used to detect the expression of Nrf2,NQO1,HO-1 mRNA in ovarian tissue relative expression.The results showed that the ovarian index of mice in BP A model group increased,the levels of GnRH,FSH,LH,E_2 and P_4 in serum and ovary decreased,and the level of ER in ovarian tissue was disordered.The effect of BPA on hormone levels in mice may be caused by oxidative stress.The content of SOD in ovarian tissue decreased,and the content of ROS and MDA increased.At the same time,the expression levels of HO-1,Nrf2,and NQO1 mRNA in the ovary were down-regulated.However,different doses of CCFs could protect the ovarian function of female mice,and down-regulale the ovarian index,hormone levels and oxidative stress indicators,which were opposite to those in the BPA group.In the present study,we demonstrated that CCFs had a certain mitigation effect on the reproductive damage caused by BPA exposure during pregnancy in female mice,especially the relatively significant alleviating effect of high-dose CCFs.