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In vivo and in vitro bisphenol A exposure effects on adiposity

Part of: DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  29 August 2018

M. Desai ,
M. G. Ferrini ,
J. K. Jellyman ,
G. Han  and
M. G. Ross
M. Desai*
Affiliation:
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
M. G. Ferrini
Affiliation:
Department of Health and Life Sciences Department of Internal Medicine, Charles R. Drew University, Los Angeles, CA, USA
J. K. Jellyman
Affiliation:
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
G. Han
Affiliation:
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
M. G. Ross
Affiliation:
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Department of Obstetrics and Gynaecology, Charles R. Drew University, Los Angeles, CA, USA
*
*Address for correspondence: M. Desai, Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street Box 446, Liu Research Bldg., Torrance, CA 90502, USA. E-mail: mdesai@labiomed.org
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Abstract

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.

Keywords

adipogenesis, bisphenol AlipogenesisPPARγproliferation and differentiation
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 6 , December 2018 , pp. 678 - 687
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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References

1. Janesick, A, Blumberg, B. Obesogens, stem cells and the developmental programming of obesity. Int J Androl. 2012; 35, 437–448.Google Scholar
2. Richter, CA, Birnbaum, LS, Farabollini, F, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007; 24, 199–224.Google Scholar
3. Rubin, BS, Soto, AM. Bisphenol A: perinatal exposure and body weight. Mol Cell Endocrinol. 2009; 304, 55–62.Google Scholar
4. Somm, E, Schwitzgebel, VM, Toulotte, A, et al. Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect. 2009; 117, 1549–1555.Google Scholar
5. Angle, BM, Do, RP, Ponzi, D, et al. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod Toxicol. 2013; 42, 256–268.Google Scholar
6. Susiarjo, M, Xin, F, Bansal, A, et al. Bisphenol A exposure disrupts metabolic health across multiple generations in the mouse. Endocrinology. 2015; 156, 2049–2058.Google Scholar
7. Alonso-Magdalena, P, Morimoto, S, Ripoll, C, Fuentes, E, Nadal, A. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006; 114, 106–112.Google Scholar
8. Alonso-Magdalena, P, Vieira, E, Soriano, S, et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect. 2010; 118, 1243–1250.Google Scholar
9. vom Saal, FS, Nagel, SC, Coe, BL, Angle, BM, Taylor, JA. The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Mol Cell Endocrinol. 2012; 354, 74–84.Google Scholar
10. Hill, JO, Wyatt, HR, Peters, JC. Energy balance and obesity. Circulation. 2012; 126, 126–132.Google Scholar
11. Ailhaud, G, Grimaldi, P, Negrel, R. Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr. 1992; 12, 207–233.Google Scholar
12. Hausman, DB, DiGirolamo, M, Bartness, TJ, Hausman, GJ, Martin, RJ. The biology of white adipocyte proliferation. Obes Rev. 2001; 2, 239–254.Google Scholar
13. Morrison, RF, Farmer, SR. Insights into the transcriptional control of adipocyte differentiation. J Cell Biochem. 1999; 32–33(Suppl.), 59–67.Google Scholar
14. Rosen, ED, Walkey, CJ, Puigserver, P, Spiegelman, BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000; 14, 1293–1307.Google Scholar
15. Darlington, GJ, Ross, SE, MacDougald, OA. The role of C/EBP genes in adipocyte differentiation. J Biol Chem. 1998; 273, 30057–30060.Google Scholar
16. Lane, MD, Lin, FT, MacDougald, OA, Vasseur-Cognet, M. Control of adipocyte differentiation by CCAAT/enhancer binding protein alpha (C/EBP alpha). Int J Obes Relat Metab Disord. 1996; 20(Suppl. 3), S91–S96.Google Scholar
17. Rosen, ED, Spiegelman, BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem. 2001; 276, 37731–37734.Google Scholar
18. Miyawaki, J, Sakayama, K, Kato, H, Yamamoto, H, Masuno, H. Perinatal and postnatal exposure to bisphenol A increases adipose tissue mass and serum cholesterol level in mice. J Atheroscler Thromb. 2007; 14, 245–252.Google Scholar
19. Chamorro-Garcia, R, Kirchner, S, Li, X, et al. Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism. Environ Health Perspect. 2012; 120, 984–989.Google Scholar
20. Masuno, H, Iwanami, J, Kidani, T, Sakayama, K, Honda, K. Bisphenol a accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol Sci. 2005; 84, 319–327.Google Scholar
21. Yee, JK, Lee, WN, Ross, MG, et al. Peroxisome proliferator-activated receptor gamma modulation and lipogenic response in adipocytes of small-for-gestational age offspring. Nutr Metab (Lond). 2012; 9, 62.Google Scholar
22. Carwile, JL, Luu, HT, Bassett, LS, et al. Polycarbonate bottle use and urinary bisphenol A concentrations. Environ Health Perspect. 2009; 117, 1368–1372.Google Scholar
23. Muhamad, MS, Salim, MR, Lau, WJ, Yusop, Z. A review on bisphenol A occurrences, health effects and treatment process via membrane technology for drinking water. Environ Sci Pollut Res Int. 2016; 23, 11549–11567.Google Scholar
24. Makris, KC, Andra, SS, Jia, A, et al. Association between water consumption from polycarbonate containers and bisphenol A intake during harsh environmental conditions in summer. Environ Sci Technol. 2013; 47, 3333–3343.Google Scholar
25. Le, HH, Carlson, EM, Chua, JP, Belcher, SM. Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicol Lett. 2008; 176, 149–156.Google Scholar
26. Mendoza-Rodriguez, CA, Garcia-Guzman, M, Baranda-Avila, N, et al. Administration of bisphenol A to dams during perinatal period modifies molecular and morphological reproductive parameters of the offspring. Reprod Toxicol. 2011; 31, 177–183.Google Scholar
27. Kabuto, H, Amakawa, M, Shishibori, T. Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci. 2004; 74, 2931–2940.Google Scholar
28. Nakajima, Y, Goldblum, RM, Midoro-Horiuti, T. Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study. Environ Health. 2012; 11, 8.Google Scholar
29. Schonfelder, G, Wittfoht, W, Hopp, H, et al. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect. 2002; 110, A703–A707.Google Scholar
30. Yoshida, M, Shimomoto, T, Katashima, S, et al. Maternal exposure to low doses of bisphenol a has no effects on development of female reproductive tract and uterine carcinogenesis in Donryu rats. J Reprod Dev. 2004; 50, 349–360.Google Scholar
31. Patisaul, HB, Sullivan, AW, Radford, ME, et al. Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy. PLoS One. 2012; 7, e43890.Google Scholar
32. Weinstock, M. Prenatal stressors in rodents: effects on behavior. Neurobiol Stress. 2017; 6, 3–13.Google Scholar
33. Mueller, BR, Bale, TL. Impact of prenatal stress on long term body weight is dependent on timing and maternal sensitivity. Physiol Behav. 2006; 88, 605–614.Google Scholar
34. Hohwu, L, Li, J, Olsen, J, Sorensen, TI, Obel, C. Severe maternal stress exposure due to bereavement before, during and after pregnancy and risk of overweight and obesity in young adult men: a Danish National Cohort Study. PLoS One. 2014; 9, e97490.Google Scholar
35. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65, 55–63.Google Scholar
36. Desai, M, Guang, H, Ferelli, M, Kallichanda, N, Lane, RH. Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring. Reprod Sci. 2008; 15, 785–796.Google Scholar
37. Vandenberg, LN, Hauser, R, Marcus, M, Olea, N, Welshons, WV. Human exposure to bisphenol A (BPA). Reprod Toxicol. 2007; 24, 139–177.Google Scholar
38. Kosarac, I, Kubwabo, C, Lalonde, K, Foster, W. A novel method for the quantitative determination of free and conjugated bisphenol A in human maternal and umbilical cord blood serum using a two-step solid phase extraction and gas chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2012; 898, 90–94.Google Scholar
39. Padmanabhan, V, Siefert, K, Ransom, S, et al. Maternal bisphenol-A levels at delivery: a looming problem? J Perinatol. 2008; 28, 258–263.Google Scholar
40. Welshons, WV, Nagel, SC, vom Saal, FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology. 2006; 147(6 Suppl.), S56–S69.Google Scholar
41. Harley, KG, Aguilar, SR, Chevrier, J, et al. Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environ Health Perspect. 2013; 121, 514–520.Google Scholar
42. Rochester, JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013; 42, 132–155.Google Scholar
43. van Esterik, JC, Dolle, ME, Lamoree, MH, et al. Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A during gestation and lactation. Toxicology. 2014; 321, 40–52.Google Scholar
44. Wei, J, Lin, Y, Li, Y, et al. Perinatal exposure to bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet. Endocrinology. 2011; 152, 3049–3061.Google Scholar
45. Bansal, A, Rashid, C, Xin, F, et al. Sex- and dose-specific effects of maternal bisphenol A exposure on pancreatic islets of first- and second-generation adult mice offspring. Environ Health Perspect. 2017; 125, 097022.Google Scholar
46. Vandenberg, LN, Maffini, MV, Sonnenschein, C, Rubin, BS, Soto, AM. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev. 2009; 30, 75–95.Google Scholar
47. Vandenberg, LN, Colborn, T, Hayes, TB, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012; 33, 378–455.Google Scholar
48. Melnick, R, Lucier, G, Wolfe, M, et al. Summary of the National Toxicology Program’s report of the endocrine disruptors low-dose peer review. Environ Health Perspect. 2002; 110, 427–431.Google Scholar
49. Diel, P, Schmidt, S, Vollmer, G, et al. Comparative responses of three rat strains (DA/Han, Sprague-Dawley and Wistar) to treatment with environmental estrogens. Arch Toxicol. 2004; 78, 183–193.Google Scholar
50. Somm, E, Schwitzgebel, VM, Toulotte, A, et al. Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect. 2009; 117, 1549–1555.Google Scholar
51. Gao, L, Wang, HN, Zhang, L, et al. Effect of perinatal bisphenol A exposure on serum lipids and lipid enzymes in offspring rats of different sex. Biomed Environ Sci. 2016; 29, 686–689.Google Scholar
52. Schneyer, A. Getting big on BPA: role for BPA in obesity? Endocrinology. 2011; 152, 3301–3303.Google Scholar
53. Wei, J, Lin, Y, Li, Y, et al. Perinatal exposure to bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet. Endocrinology. 2011; 152, 3049–3061.Google Scholar
54. Tremblay-Franco, M, Cabaton, NJ, Canlet, C, et al. Dynamic metabolic disruption in rats perinatally exposed to low doses of bisphenol-A. PLoS One. 2015; 10, e0141698.Google Scholar
55. Manikkam, M, Tracey, R, Guerrero-Bosagna, C, Skinner, MK. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One. 2013; 8, e55387.Google Scholar
56. Nagel, SC, vom Saal, FS, Welshons, WV. Developmental effects of estrogenic chemicals are predicted by an in vitro assay incorporating modification of cell uptake by serum. J Steroid Biochem Mol Biol. 1999; 69, 343–357.Google Scholar
57. Montano, MM, Welshons, WV, vom Saal, FS. Free estradiol in serum and brain uptake of estradiol during fetal and neonatal sexual differentiation in female rats. Biol Reprod. 1995; 53, 1198–1207.Google Scholar
58. Nunez, EA, Benassayag, C, Savu, L, Vallette, G, Delorme, J. Oestrogen binding function of alpha 1-fetoprotein. J Steroid Biochem. 1979; 11, 237–243.Google Scholar
59. Milligan, SR, Khan, O, Nash, M. Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and to sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss) plasma. Gen Comp Endocrinol. 1998; 112, 89–95.Google Scholar
60. Hudak, CS, Sul, HS. Pref-1, a gatekeeper of adipogenesis. Front Endocrinol(Lausanne). 2013; 4, 79.Google Scholar
61. Wang, Y, Hudak, C, Sul, HS. Role of preadipocyte factor 1 in adipocyte differentiation. Clin Lipidol. 2010; 5, 109–115.Google Scholar
62. Wang, Y, Sul, HS. Pref-1 regulates mesenchymal cell commitment and differentiation through Sox9. Cell Metab. 2009; 9, 287–302.Google Scholar
63. Ailhaud, G, Amri, E, Bardon, S, et al. The adipocyte: relationships between proliferation and adipose cell differentiation. Am Rev RespirDis. 1990; 142(6 Pt 2), S57–S59.Google Scholar
64. Faust, IM, Miller, WH Jr, Sclafani, A, et al. Diet-dependent hyperplastic growth of adipose tissue in hypothalamic obese rats. Am J Physiol. 1984; 247(6 Pt 2), R1038–R1046.Google Scholar
65. Miller, WH Jr., Faust, IM, Hirsch, J. Demonstration of de novo production of adipocytes in adult rats by biochemical and radioautographic techniques. J Lipid Res. 1984; 25, 336–347.Google Scholar
66. Wabitsch, M. The acquisition of obesity: insights from cellular and genetic research. Proc Nutr Soc. 2000; 59, 325–330.Google Scholar
67. Masuno, H, Kidani, T, Sekiya, K, et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J Lipid Res. 2002; 43, 676–684.Google Scholar
68. Phrakonkham, P, Viengchareun, S, Belloir, C, et al. Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis. J Steroid Biochem Mol Biol. 2008; 110, 95–103.Google Scholar
69. Sargis, RM, Johnson, DN, Choudhury, RA, Brady, MJ. Environmental endocrine disruptors promote adipogenesis in the 3T3-L1 cell line through glucocorticoid receptor activation. Obesity (SilverSpring). 2010; 18, 1283–1288.Google Scholar
70. Boucher, JG, Boudreau, A, Atlas, E. Bisphenol A induces differentiation of human preadipocytes in the absence of glucocorticoid and is inhibited by an estrogen-receptor antagonist. Nutr Diabetes. 2014; 4, e102.Google Scholar
71. Valentino, R, D'Esposito, V, Passaretti, F, et al. Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells. PLoS One. 2013; 8, e82099.Google Scholar
72. Lee, JE, Ge, K. Transcriptional and epigenetic regulation of PPARgamma expression during adipogenesis. Cell Biosci. 2014; 4, 29.Google Scholar
73. Bauer, RC, Sasaki, M, Cohen, DM, et al. Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPalpha. J Clin Invest. 2015; 125, 3809–3818.Google Scholar
74. Bastos, SL, Kamstra, JH, Cenijn, PH, et al. Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicol In Vitro. 2013; 27, 1634–1643.Google Scholar
75. Kundakovic, M, Champagne, FA. Epigenetic perspective on the developmental effects of bisphenol A. Brain Behav Immun. 2011; 25, 1084–1093.Google Scholar
76. Adamo, A, Sese, B, Boue, S, et al. LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat Cell Biol. 2011; 13, 652–659.Google Scholar
77. Fujiki, K, Kano, F, Shiota, K, Murata, M. Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol. 2009; 7, 38.Google Scholar
78. Musri, MM, Carmona, MC, Hanzu, FA, et al. Histone demethylase LSD1 regulates adipogenesis. J Biol Chem. 2010; 285, 30034–30041.Google Scholar
79. Zych, J, Stimamiglio, MA, Senegaglia, AC, et al. The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells. Braz J Med Biol Res. 2013; 46, 405–416.Google Scholar
80. Hervouet, E, Vallette, FM, Cartron, PF. Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics. 2009; 4, 487–499.Google Scholar
81. Strakovsky, RS, Wang, H, Engeseth, NJ, et al. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis. Toxicol Appl Pharmacol. 2015; 284, 101–112.Google Scholar
82. Lejonklou, MH, Dunder, L, Bladin, E, et al. Effects of low-dose developmental bisphenol A exposure on metabolic parameters and gene expression in male and female fischer 344 rat offspring. Environ Health Perspect. 2017; 125, 067018.Google Scholar
83. Kundakovic, M, Gudsnuk, K, Franks, B, et al. Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc Natl Acad Sci USA. 2013; 110, 9956–9961.Google Scholar
84. Yang, TC, Peterson, KE, Meeker, JD, et al. Bisphenol A and phthalates in utero and in childhood: association with child BMI z-score and adiposity. Environ Res. 2017; 156, 326–333.Google Scholar
85. Rubin, BS, Paranjpe, M, DaFonte, T, et al. Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: the addition of peripubertal exposure exacerbates adverse effects in female mice. Reprod Toxicol. 2017; 68, 130–144.Google Scholar
86. Susiarjo, M, Sasson, I, Mesaros, C, Bartolomei, MS. Bisphenol a exposure disrupts genomic imprinting in the mouse. PLoS Genet. 2013; 9, e1003401.Google Scholar
87. Ding, S, Fan, Y, Zhao, N, et al. High-fat diet aggravates glucose homeostasis disorder caused by chronic exposure to bisphenol A. J Endocrinol. 2014; 221, 167–179.Google Scholar
88. Perreault, L, McCurdy, C, Kerege, AA, et al. Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. PLoS One. 2013; 8, e69991.Google Scholar
89. Grundy, D. Principles and standards for reporting animal experiments in The. Journal of Physiology and Experimental Physiology. Exp Physiol . 2015; 100, 755–758.Google Scholar