Research of Bisphenol A Exposure Interfering Ovarian Development in Offspring Mice (Mus musculus)
ZHANG Shi-Lei1,2, BAO Jia-Lu2, SHI Wan-Yu2, ZHONG Xiu-Hui1,2,*
1 College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, China; 2 College of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Baoding 071001, China
Abstract：Bisphenol A (BPA) is a ubiquitous environmental endocrine disruptor. This study was conducted to investigate the effects of BPA exposure to the dams during gestation and lactation on ovarian development in offspring. In this experiment, 8-week-old female mice (Mus musculus) at pregnant 0 d were randomly divided into 7 groups with 20 each group, and distilled water and 0.05, 0.5, 5, 10, 20, 50 mg / kg BPA were given through drinking water from 0 d pregnant to 21 d weaned. In this test, the offspring mice did not directly contact BPA, but indirectly contacted BPA through placental transmission and lactation during breastfeeding. And the mice gave birth at 20 d of pregnancy, so the indirect contact time of BPA was 41 d. The period of exposure was from gestation day 0 until the weaning of the F1 mice for 41 d. The results showed that the BPA content in the serum and ovary of the offspring mice was significantly increased when the dose of BPA≥20 mg/kg (P<0.05). Organ index showed that the dose of BPA≥10 mg/kg resulted in a significant increase in the ovarian index of the pups (P<0.05). The observation of hematoxylin-eosin staining (HE) pathological tissue sections showed that low doses of BPA (≥0.05 mg/kg) could damage the ovaries of the offspring and cause irregular architecture in follicular granule cell layers. And the pathological changes of the ovary also increase as the dose increases. The results of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) showed that the ovarian granulosa cells were apoptotic when the BPA exposure was at or over 20 mg/kg (P<0.05). The expression of estrogen receptor α (ERα) in the ovary significantly increased when BPA exposed at no less than 20 mg/kg (P<0.05). And the dose of BPA of 50 mg/kg had significant affect on ERβ expression in ovarian progeny 21-day-old mice. The results of transcriptome sequencing showed that there were 81 significant differentially expressed genes in the ovary of the offspring compared with the control group, 38 of which were up-regulated and 43 genes were down-regulated. Differentially expressed genes were enriched in transcriptional functions and ribosomal metabolic pathways, in which the ribosomal genes ribosomal protein L3 (Rpl3), Rpl21 and Rpsa were significantly down-regulated, and the Rps2、Rps28、Rpl26、Rpl32 and Rpl10a were significantly up-regulated. These genes are associated with developmental arrest of the reproductive system of the embryo, apoptosis and ovarian precocity. The expression levels of Rps2, Rpl21 and Rpsa in all 7 groups of ovarian were detected by real-time PCR, which was consistent with the results of transcriptome, but the effect of BPA on Rps2 varied with doses. When BPA dose was 0.05 mg/kg to 20 mg/kg, the expression of Rps2 was lower than that of the control group, but the expression level was higher than that of the control group at the dose of 50 mg/kg. These results indicated that BPA could be indirectly transmitted to progeny mice through the placenta and milk of maternal mice. Ingestion of BPA could cause lesions in the ovaries of offspring mice, affected the development and function of the ovaries. Further studies at the genetic level revealed that abnormalities in ribosomal functional protein synthesis were associated with reproductive toxicity of BPA, and that low-dose BPA inhibited ribosomal protein expression while high-dose BPA promoted ribosomal protein expression, demonstrating the duality of BPA in ovarian development. The difference in doses used may be the reason for the current contradiction in the results of the BPA study. In this study, the offspring mice did not directly contact BPA, but the ovarian development of the pups was still affected by BPA, and it was further confirmed that BPA disrupted the normal ovarian development by affecting ovarian ribosomal function. The results of this study imply that the use of BPA-containing plastic products in pregnant livestock may affect offspring ovarian development, Which means that avoiding the use of BPA-containing plastic products in livestock breeding can help ensure the reproductive health of offspring, improve the breeding efficiency of livestock.
张石磊, 包佳鹭, 史万玉, 钟秀会. 环境雌激素双酚A暴露干扰仔鼠卵巢发育的研究[J]. 农业生物技术学报, 2020, 28(1): 108-118.
ZHANG Shi-Lei, BAO Jia-Lu, SHI Wan-Yu, ZHONG Xiu-Hui. Research of Bisphenol A Exposure Interfering Ovarian Development in Offspring Mice (Mus musculus). 农业生物技术学报, 2020, 28(1): 108-118.
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