|
|
|
| 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.
|
|
Received: 16 July 2019
|
|
|
|
Corresponding Authors:
*zxh8078@163.com
|
|
|
|
[1] 白泽清. 2018. 啤酒易拉罐中苯酚和双酚A的迁移检测[J]. 包装工程, 39(09): 92-95.
(Bai Z Q2018. Migration detection of phenol and bisphenol A in beer cans[J]. Packaging Engineering, 39(09): 92-95.)
[2] 李俊宪, 谢明. 2011. 核糖体蛋白质L21在小鼠下颌磨牙牙胚发育过程中的特异性原位表达[J]. 安徽医科大学学报, 46(8): 729-732.
(Li J X, Xie M.2011. Specific in situ expression of ribosomal protein L21 during development of mouse mandibular molars[J]. Acta Universitatis Medicinalis Anhui, 46(8): 729-732.)
[3] 刘敏, 尹龙龙, 赵雪桢, 等. 2018. 泰安市塑料桶装白酒中双酚A含量检测及居民膳食风险评估[J]. 食品安全质量检测学报, 9(10): 2564-2568.
(Liu M, Yin L L, Zhao X Y, et al.2018. Determination of bisphenol A in plastic bottled spirits and risk assessment for the population in Taian city[J]. Journal of Food Safety and Quality, 9(10): 2564-2568.)
[4] 邵一鸣, 张玉彬, 周志俊. 2018. 孕期双酚A暴露对子代影响的流行病学研究进展[J]. 环境与职业医学, 35(10): 959-965.
(Shao Y M, Zhang Y B, Zhou Z J.2018. Advances in epidemiological studies on the effects of bisphenol A exposure on offspring during pregnancy[J]. Journal of Environmental and Occupational Medicine, 35: 959-965.)
[5] Ahmed R G.2016. Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction[J]. Food Chemical Toxicology, 95: 168-174.
[6] Chen J, Xiao Y, Gai Z, et al.2015. Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects[J]. Aquatic Toxicology, 169: 204-214.
[7] Corrales J, Kristofco L A, Steele W B, et al.2015. Global assessment of bisphenol A in the environment: Review and analysis of its occurrence and bioaccumulation[J]. Dose Response Relationship 13(3):15593258-15598308.
[8] Estep A S, Sanscrainte N D, Becnel J J.2016. DsRNA-mediated targeting of ribosomal transcripts RPS6 and RPL26 induces long-lasting and significant reductions in fecundity of the vector aedes aegypti[J]. Journal of Insect Physiology, 90: 17-26.
[9] Fenner-crisp P A, Maciorowski A F, Timm G E.2000. The endocrine disruptor screening program developed by the U.S. environmental Protection Agency[J]. Ecotoxicology, 59(3): 85-91
[10] Hall D E, Frazer K A, Hann B C, et al.2013. Isolation and characterization of a laminin-binding protein from rat and chick muscle[J]. Journal of Cell Biology, 107(2): 687-697.
[11] Hiyama M, Choie K, Wakitani S, et al.2011. Bisphenol A (BPA) affects reproductive formation across generations in mice[J]. The Journal of Veterinary Medical Science, 73(9): 1211-1215.
[12] Hu Y, Wen S, Yuan D, et al.2018. The association between the environmental endocrine disruptor bisphenol A and polycystic ovary syndrome: a systematic review and meta-analysis[J]. Gynecological Endocrinology, 34(5): 370-377.
[13] Huang R, Liu Z, Yuan S, et al.2017. Worldwide human daily intakes of bisphenol A (BPA) estimated from global urinary concentration data (2000-2016) and its risk analysis[J]. Environment Pollution, 230: 143-152.
[14] Huang Y Q, Wong C K C, Zheng J S, et al.2012. Bisphenol A (BPA) in China: A review of sources, environmental lev nd potential human health impacts[J]. Environment International, 42: 91-99.
[15] Izumi N, Yanagibori R, Shigeno S, et al.2008. Effects of bisphenol A on the development, growth, and sex ratio of the housefly Musca domestica[J]. Environmental Toxicology and Chemistry, 27(6): 1343-1353.
[16] Javurek A B, Spollen W G, Johnson S A, et al.2016. Effects of exposure to bisphenol A and ethinyl estradiol on the gut microbiota of parents and their offspring in a rodent model[J]. Gut Microbes, 7: 471-485.
[17] Kleene K C, Cataldo L, Mastrangelo M A, et al.2003. Alternative patterns of transcription and translation of the ribosomal protein L32 mRNA in somatic and spermatogenic cells in mice[J]. Experimental Cell Research, 291: 101-110.
[18] Kowalczyk P, Woszczynski M, Ostrowski J.2002. Increased expression of ribosomal protein S2 in liver tumors, posthepactomized livers, and proliferating hepatocytes in vitro[J]. Acta Biochimica Polonica, 49: 615-624.
[19] Kuiper G G, Lemmen J G, Carlsson B, et al.1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta[J]. Endocrinology, 139: 4252-4263.
[20] Machtinger R, Berman T, Adir M, et al.2018. Urinary concentrations of phthalate metabolites, bisphenols and personal care product chemical biomarkers in pregnant women in Israel[J]. Environment International, 116: 319-325.
[21] Mandrup K, Boberg J, Isling L K, et al.2016. Low-dose effects of bisphenol A on mammary gland development in rats[J]. Andrology, 4: 673-683.
[22] Monwadee W, Wilaiwan C, Allison T, et al.2011. RpL10A regulates oogenesis progression in the banana prawn Fenneropenaeus merguiensis and Drosophila melanogaster[J]. General and Comparative Endocrinology, 173: 356-363.
[23] Moreman J, Lee O, Trznadel M, et al2017. Acute toxicity, teratogenic and estrogenic effects of Bisphenol A and its alternative replacements Bisphenol S, Bisphenol F and Bisphenol AF in zebrafish embryo-larvae[J]. Environmental Science & Technology, 51: 12796-12805.
[24] Pennie W D, Aldridge T C, Brooks A N, 1998. Differential activation by xenoestrogens of ER alpha and ER beta when linked to different response elements[J]. Journal of Endocrinology, 158: R11-14.
[25] Percharde M, Wong P, Ramalho-santos M.2017. Global hypertranscription in the mouse embryonic germline[J]. Cell Reports, 19: 1987-1996.
[26] Santonicola S, Ferrante M C, Leo G D, et al.2018. Study on endocrine disruptors levels in raw milk from cow's farms: Risk assessment[J]. The Italian Journal of Food Safety, 7: 7668.
[27] Schonfelder G, Wittfoht W, Hopp Het al.2002. Parent bisphenol A accumulation in the human maternal-fetal-placental unit[J]. Environmental Health Perspectives, 110: A703-707.
[28] Takeuchi T, Tsutsumi O, Ikezuki Y, et al.2004. Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction[J]. Endocrine Journal, 51: 165-169.
[29] Vermeirssen E, Dietschweiler C, Werner I, et al.2017. Corrosion protection products as a source of bisphenol A and toxicity to the aquatic environment[J]. Water Research, 123: 586-593.
[30] Vilas-boas F, Bagulho A, Tenente R, et al.2016. Hydrogen peroxide regulates cell adhesion through the redox sensor RPSA[J]. Free Radical Biology and Medicine, 90: 145-157.
[31] Wang J, Yuan S, Jiang S2006. The ribosomal protein L32-2 (RPL32-2) of S. pombe exhibits a novel extraribosomal function by acting as a potential transcriptional regulator[J]. FEBS Letters, 580: 1827-1832.
[32] Wang X, Jiang S W, Wang L, et al.2018. Interfering effects of bisphenol A on in vitro growth of preantral follicles and maturation of oocytes[J]. Clinica Chimica Acta, 485: 119-125.
[33] Xu J, Osuga Y, Yano T, et al.2002. Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells[J]. Biochemical and Biophysical Research Communications, 292: 456-462.
[34] Zhang Y, Wei F, Zhang J, et al.2017. Bisphenol A and estrogen induce proliferation of human thyroid tumor cells via an estrogen-receptor-dependent pathway[J]. Archives of Biochemistry and Biophysics, 633: 29-39. |
|
|
|
