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. 2018 Dec;9(6):678-687.
doi: 10.1017/S2040174418000600. Epub 2018 Aug 29.

In Vivo and in Vitro Bisphenol A Exposure Effects on Adiposity

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Free PMC article

In Vivo and in Vitro Bisphenol A Exposure Effects on Adiposity

M Desai et al. J Dev Orig Health Dis. .
Free PMC article

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: bisphenol A; PPARγ; adipogenesis; lipogenesis; proliferation and differentiation.

Conflict of interest statement

CONFLICTS OF INTEREST: None

Figures

Figure 1A:
Figure 1A:. Effects of Maternal BPA Exposure on Maternal Body Weights, Food Intake and Water Intake Maternal daily body weights and water intake during pregnancy and lactation of BPA (□) and Control (■) dams. Values are means±SE of n=5 litters. Figure 1B: Effects of Maternal BPA Exposure on Maternal Body Fat
Maternal body fat and retroperitoneal adipocyte cell size and images (scale bar = 100µm) at end of lactation of BPA (□) and Control (■) dams. Values are means±SE of n=5 litters.
Figure 2:
Figure 2:. Maternal BPA Effects on Offspring Body Weights
Body weights of 1 day old newborns, and body weights of 3 and 24 weeks old male and female offspring. Values are means±SE of n=5 from 5 litters per group; * p<0.05 BPA (□) vs. Control (■).
Figure 3:
Figure 3:. Maternal BPA Effects on Offspring Adiposity
Percentage body fat of 3 and 24 weeks old male and female offspring. Values are means±SE of n=5 from 5 litters per group; * p<0.05 BPA (□) vs. Control (■).
Figure 4:
Figure 4:. Maternal BPA Effects on Offspring Blood Pressure
Systolic blood pressure of 6 weeks old male and female offspring. Values are means±SE of n=5 from 5 litters per group; * p<0.05 BPA (□) vs. Control (■).
Figure 5:
Figure 5:. Maternal BPA Effects on Offspring Adipogenic and Lipogenic Factors
(a) Inguinal adipose tissue protein expression of PPARγ and C/EBPα in 1 day old male newborns, (b) Retroperitoneal adipose protein expression of PPARγ, C/EBPα and SREBP1, and (c) retroperitoneal adipocyte cell size and images (scale bar = 100µm) in 3 week old male offspring. Values are means±SE of n=5 of pooled adipose from each of 5 litters per group; * p<0.05 BPA (□) vs. Control (■).
Figure 6:
Figure 6:. Maternal BPA Effects on Adipose Tissue Inflammation in 3 Week Old Male Offspring
Retroperitoneal adipose protein expression of CD68 and TNFα in 3 week old male offspring. Values are means±SE of n=5 of pooled adipose from each of 5 litters per group; * p<0.05 BPA (□) vs. Control (■).
Figure 7:
Figure 7:. In Vitro BPA Effects on Preadipocytes
Inguinal adipose tissue from 1 day old Control newborns were cultured in DMEM (undifferentiated) media and treated with DMSO (Control) or BPA (0, 1, 10, 20 µM) for 5 days. (a) Preadipocyte image, (b) proliferative index measured at 520 OD and (c) protein expression of Pref1 and Sox9 (results are shown for two doses due to loss of 20 µM BPA protein extract) with representative blot shown. Values are fold change (mean±SE) of n=4 of pooled adipose from each of 4 litters; * P< 0.05 BPA (□) vs. Control (■).
Figure 8:
Figure 8:. In Vitro BPA Effects on Differentiated Adipocytes
Inguinal adipose tissue from 1 day old Control newborns were cultured in DMEM media and preadipocytes were allowed to differentiate in presence of BPA for 5 days. (a) Protein expression of PPARγ and C/EBPα with representative blot shown. (b) Adipocytes were fixed with 4% paraformaldehyde and stained for lipid (Oil Red O; red) and nucleus (DAPI; blue). Scale bar = 100µm. Protein expression of SREBP1 with representative blot shown and lipid content. Values are fold change (mean±SE) of n=4 of pooled adipose from each of 4 litters;* P< 0.05 BPA (□) vs. Control (■).
Figure 9:
Figure 9:. In Vitro BPA Effects on Epigenetic Factors
Inguinal preadipocytes from 1 day old Control newborns were cultured in DMEM media with BPA (1, 10, 20 µM) for 5 days. Protein expression of DNMT3a and LSD1 with representative blot shown. Values are fold change (mean±SE) of pooled cells n=4 from each of 4 litters; * P<0.05 BPA (□) vs. Control (■).

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