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Multigenerational and transgenerational effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on ovarian reserve and follicular development through AMH/AMHR2 pathway in adult female rats.
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-03-29 , DOI: 10.1016/j.fct.2020.111309
Kailun Yu 1 , Xiuli Zhang 2 , Xuemei Tan 1 , Mengmeng Ji 3 , Yao Chen 1 , Zhongxiao Wan 1 , Zengli Yu 1
Affiliation  

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), one of the key endocrine disruptors, has been shown to cause reproductive and developmental disorders. Our previous studies have primarily focused on TCDD induced impairment of ovarian follicular development in female F1 rats. It is unknown whether TCDD exposure will interfere with follicular development by altering mRNA expression of anti-Müllerian hormone (AMH) and AMH receptor type II (AMHR2) in the ovary. In the present study, pregnant Sprague Dawley rats were treated with TCDD (100 or 500 ng/kg body weight) dissolved in a corn oil vehicle by gavage from gavage from gestational days (GD) 8-14, while the control group received solely corn oil. The F1 rats were mated with unexposed males for the F2 generation, while another portion of the female offspring (F2) were mated for the F3 generation. Serum AMH levels and ovarian AMH/AMHR2 mRNA expression in the adult female offspring (F1, F2 and F3 generations) were measured. Follicle count and granulosa cell apoptosis were evaluated in the F2 and F3 generations. The results showed that in the F2 generation, TCDD exposure affected the number of primordial follicles, secondary follicles, and corpora lutea. It also increased serum AMH concentration and the apoptosis rate of granulosa cells. These results might be associated with the upregulation of AMH/AMHR2 mRNA expression in the ovary. In conclusion, TCDD exposure reduced the ovarian reserve in rats and inhibited follicular development in adult female offspring, an effect that persisted for multiple generations. The altered AMH and AMHR2 mRNA expression may contribute to the observed adverse effects.

中文翻译:

2,3,7,8-四氯二苯并-p-二恶英暴露对成年雌性大鼠卵巢储备和卵泡发育的多代和跨代影响。

2,3,7,8-四氯苯并-对-二恶英(TCDD)是主要的内分泌干扰物之一,已被证明会引起生殖和发育障碍。我们以前的研究主要集中在TCDD诱导的雌性F1大鼠卵巢卵泡发育损害中。尚不清楚TCDD暴露是否会通过改变卵巢中的抗苗勒氏激素(AMH)和II型AMH受体(AMHR2)的mRNA表达来干扰卵泡发育。在本研究中,对怀孕的Sprague Dawley大鼠进行了TCDD(100或500 ng / kg体重)治疗,方法是将其从妊娠第8至14天的管饲法中灌入玉米油载体中,而对照组则仅接受玉米油。将F1大鼠与未暴露的雄性交配以繁殖F2代,而将另一部分雌性后代(F2)交配以产生F3代。测量了成年雌性后代(F1,F2和F3代)的血清AMH水平和卵巢AMH / AMHR2 mRNA表达。在F2和F3代中评估卵泡计数和颗粒细胞凋亡。结果表明,在F2代中,TCDD暴露会影响原始卵泡,次级卵泡和黄体的数量。它还增加了血清AMH浓度和颗粒细胞的凋亡率。这些结果可能与卵巢中AMH / AMHR2 mRNA表达的上调有关。总之,暴露于TCDD会降低大鼠的卵巢储备并抑制成年雌性后代的卵泡发育,这种作用持续了多代。改变的AMH和AMHR2 mRNA表达可能有助于观察到的不良反应。
更新日期:2020-03-31
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