Bisphenol A (BPA) is one of the most commonly produced chemicals in the world. BPA is used in products such as food packaging, personal care products, detergents, and plastic bottles. This study was conducted to determine the effect of BPA on fetal bone development.
Material and methods:
In this study, 16 pregnant female Sprague-Dawley rats were used. The rats were divided into four groups: the control group and 0.5 mg/kg/day, 5 mg/kg/day, and 50 mg/kg/day dose BPA groups. The skeletal system development of fetuses was examined with double skeletal and immunohistochemistry (IHC) staining (tartrate resistant acid phosphatase (TRAP) and the alkaline phosphatase (AP) expressions) methods.
Results:
The highest ossification rates in the humerus, radius, and ulna were detected as 41.05%, 39.25%, and 37.26% in the control group, respectively. The highest ossification rates in the femur, tibia, and fibula were detected as 23.04%, 30.73%, and 32.78% in the control group, respectively. Statistically significant differences were found between control and experimental groups in the TRAP and AP expression of the femur by IHC staining (p < 0.001).
Conclusion:
Exposure to BPA during pregnancy adversely affected ossification and bone growth. A dose-dependent decrease was observed in the rate of ossification.
AgasDSabbietiMGMarchettiL (2013) Endocrine disruptors and bone metabolism. Archives of Toxicology87(4): 735–751.
2.
Alonso-MagdalenaPRoperoABSorianoS. (2012) Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways. Molecular and Cellular Endocrinology355(2): 201–207.
3.
ArbuckleTEDavisKMarroL. (2014) Phthalate and bisphenol A exposure among pregnant women in Canada-results from the MIREC study. Environment International68: 55–65.
4.
BergeronRMThompsonTBLeonardLS. (1999) Estrogenicity of bisphenol A in a human endometrial carcinoma cell line. Molecular and Cellular Endocrinology150(1-2): 179–187.
5.
BjörnsdotterMKde BoerJBallesteros-GómezA (2017) Bisphenol A and replacements in thermal paper: a review. Chemosphere182: 691–706.
BolliAGalluzzoPAscenziP. (2008) Laccase treatment impairs bisphenol A-induced cancer cell proliferation affecting estrogen receptor alpha-dependent rapid signals. International Union of Biochemistry and Molecular Biology Life60: 843–852.
8.
CalafatAMKuklenyikZReidyJA. (2005) Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environmental Health Perspectives113(4): 391–395.
9.
CasasMValviDLuqueN. (2013) Dietary and sociodemographic determinants of Bisphenol A urine concentrations in pregnant women and children. Environment International56: 10–18.
10.
ChristensonRH (1997) Biochemical markers of bone metabolism: an overview. Clinical Biochemistry30(8): 573–593.
11.
DanielsonMKihlströmI (1986) Calcification of the rabbit fetal skeleton. Growth50(3): 378–384.
DornPBChouCSGentempoJJ (1987) Degradation of bisphenol A in natural waters. Chemosphere16(7): 1501–1507.
14.
DodsonRENishiokaMStandleyLJ. (2012) Endocrine disruptors and asthma-associated chemicals in consumer products. Environmental Health Perspectives120(7): 935–943.
15.
European Food Safety Authority (EFSA) (2015) Scientific opinion on the risks to public health related to the presence of Bisphenol A (BPA) in foodstuffs: executive summary. EFSA Journal13(1): 3978.
16.
EvansHESackWO (1973) Prenatal development of domestic and laboratory mammals: growth curves, external features and selected references. Anatomia, Histologia, Embryologia2: 11–45.
17.
FernandezMFArrebolaJPTaoufikiJ. (2007) Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reproductive Toxicology24(2): 259–264.
18.
GeensTAertsDBerthotC. (2012) A review of dietary and non-dietary exposure to bisphenol-A. Food and Chemical Toxicology50(10): 3725–3740.
19.
HardinBDBondGPSikovMR. (1981) Testing of selected workplace chemicals for teratogenic potential. Scandinavian Journal of Work, Environment and Health7(4): 66–75.
20.
HarleyKGAguilar SchallRChevrierJ. (2013) Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environmental Health Perspectives121(4): 514–520.
21.
HebelRStrombergMW (1986) Anatomy and embryology of the laboratory rat. BioMed Verlag Wörthsee9-21: 231–251.
22.
HwangJKMinKHChoiKH. (2013) Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sciences93(9-11): 367–372.
23.
IchikawaTHorie-InoueKIkedaK. (2006) Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. The Journal of Biological Chemistry281(25): 16927–16934.
24.
IkezukiYTsutsumiOTakaiY. (2002) Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Human Reproduction17(11): 2839–2841.
25.
KannoSHiranoSKayamaF (2004) Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells. Toxicology196 (1–2): 137–145.
26.
KangJHKondoFKatayamaY (2006) Human exposure to bisphenol A. Toxicology226(2–3): 79–89.
27.
KimJCShinHCChaSW. (2001) Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy. Life Sciences69(22): 2611–2625.
28.
KiniUNandeeshBN (2012) Physiology of bone formation, remodeling, and metabolism. In: FogelmanIGnanasegaranGvan der WallH (eds), Radionuclide and Hybrid Bone Imaging. Verlag Berlin Heidelberg: Springer, p. 39.
29.
KostevaJLangerC (2008) The changing landscape of the medical management of skeletal metastases in nonsmall cell lung cancer. Current Opinion in Oncology20(2): 155–161.
30.
KousteniSAlmeidaMHanL. (2007) Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor. Molecular and Cellular Biology27(4): 1516–1530.
31.
KuiperGGLemmenJGCarlssonB. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology139(10): 4252–4263.
32.
LejonklouMHChristiansenSÖrbergJ. (2016) Low-dose developmental exposure to bisphenol A alters the femoral bone geometry in Wistar rats. Chemosphere164: 339–346.
33.
LiDKZhouZMiaoM. (2011) Urine bisphenol-A (BPA) level in relation to semen quality. Fertility and Sterility95(2): 625–630.
34.
LindTLejonklouMHDunderL. (2017) Low-dose developmental exposure to bisphenol A induces sex-specific effects in bone of Fischer 344 rat offspring. Environmental Research159: 61–68.
35.
MaffiniMVRubinBSSonnenscheinC. (2006) Endocrine disruptors and reproductive health: the case of bisphenol-A. Molecular and Cellular Endocrinology254-255: 179–186.
36.
MarshallWJ (1988) Illustrated Textbook of Clinical Chemistry, 1st ed. London: Gower Medical, p. 65.
37.
MendumTStolerEVan BenschotenH. (2011) Concentration of bisphenol A in thermal paper. Green Chemistry Letters and Reviews4(1): 81–86.
38.
MenegolaEBrocciaMLGiaviniE (2001) Atlas of rat fetal skeleton double stained for bone and cartilage. Teratology64(3): 125–133.
39.
Merchant Research & Consulting (2014) Bisphenol A (BPA): 2014 World Market Outlook and Forecast up to 2018. Limassol: TD The Market, pp. 1–3.
40.
MigliaccioSNewboldRRBullockBC. (1996) Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring. Endocrinology137(5): 2118–2125.
41.
MikiYHataSNagasakiS. (2016) Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts. Life Sciences155: 29–35.
42.
MiyakodaHTabataMOnoderaS. (1999) Passage of bisphenol A into the fetus of the pregnant rat. Journal of Health Sciences45(6): 318–323.
43.
MiyakodaHTabataMOnoderaS. (2000) Comparison of conjugative activity, conversion of bisphenol A to bisphenol A glucuronide, in fetal and mature male rat. Journal of Health Sciences46(4): 269–274.
44.
MorganMKNashMBarrDB. (2018) Distribution, variability, and predictors of urinary bisphenol A levels in 50 North Carolina adults over a six-week monitoring period. Environment International112: 85–99.
45.
MorrisseyREGeorgeJDPriceCJ. (1987) The developmental toxicity of bisphenol A in rats and mice. Fundamental and Applied Toxicology8(4): 571–582.
PelchKECarletonSMPhillipsCL. (2012) Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice. Biology of Reproduction86(3): 69.
48.
PriceCPKirwanAVaderC (1995) Tartrate-resistant acid phosphatase as a marker of bone resorption. Clinical Chemistry41(5): 641–643.
49.
RodanGA (1992) Introduction bone biology. Bone13: 3–6.
50.
RubinBS (2011) Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. The Journal of Steroid Biochemistry and Molecular Biology127(1–2): 27–34.
51.
SadeghiF (2014) Two separated protocols with the most important comments for skeletal staining in embryonic and adulthood period in laboratory animals. Anatomical Sciences11(2): 87–92.
52.
SchönfelderGWittfohtWHoppH. (2002) Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environmental Health Perspectives110(11): A703–A707.
53.
SelinskiSDegenGH (2004) Comparison of the toxicokinetics of daidzein and bisphenol A in pregnant and non-pregnant DA/Han rats. Technical Report/Universität Dortmund41: 1–21.
54.
ShelbyMD (2008) NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A. NTP Cerhr Mon (22): v, vii–ix, 1–64passim. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19407859.
55.
SonneCDietzRBornEW. (2004) Is bone mineral composition disrupted by organochlorines in east Greenland polar bears (Ursus maritimus)?Environmental Health Perspectives112(17): 1711–1716.
56.
SrivastavaSToraldoGWeitzmannMN. (2001) Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. The Journal of Biological Chemistry276(12): 8836–8840.
57.
SuzukiNHattoriA (2003a) Bisphenol A suppresses osteoclastic and osteoblastic activities in the cultured scales of goldfish. Life Sciences73(17): 2237–2247.
58.
SuzukiNKambegawaAHattoriA (2003b) Bisphenol A influences the plasma calcium level and inhibits calcitonin secretion in goldfish. Zoological Science20(6): 745–748.
59.
TabbMMSunAZhouC. (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. The Journal of Biological Chemistry278(45): 43919–43927.
60.
TachibanaTWakimotoYNakamutaN. (2007) Effects of bisphenol A (BPA) on placentation and survival of the neonates in mice. Journal of Reproduction and Development53(3): 509–514.
61.
TsukamotoYIshiharaYMiyagawa-TomitaS. (2004) Inhibition of ossification in vivo and differentiation of osteoblasts in vitro by tributyltin. Biochemical Pharmacology68(4): 739–746.
62.
VandenbergLNHuntPAMyersJP. (2013) Human exposures to bisphenol A: mismatches between data and assumptions. Reviews on Environmental Health28(1): 37–58.
63.
Van LanduytKLNawrotTGeebelenB. (2011) How much do resin-based dental materials release? A meta-analytical approach. Dental Materials27(8): 723–747.
64.
Vom SaalFSWelshonsWV (2006) Large effects from small exposures in the importance of positive controls in low-dose research on bisphenol A. Environmental Research100(1): 50–76.
65.
WoodruffTJZotaARSchwartzJM (2011) Environmental chemicals in pregnant women in the United States: NHANES 2003–2004. Environmental Health Perspectives119(6): 878–885.
66.
World Health Organization (2010) Toxicological and Health Aspect of Bisphenol A. Ottawa: Report of Joint FAO/WHO Expert Meeting, pp. 17–40.
67.
XinFSmithLMSusiarjoM. (2018) Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system. Environmental Epigenetics4(2): dvy002.
68.
YamadaHFurutaIKatoEH. (2002) Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester. Reproductive Toxicology16: 735–739.
69.
YangYJHongYCOhSY. (2009) Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women. Environmental Research109(6): 797–801.
70.
YeXKuklenyikZNeedhamLL. (2005) Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry383: 638–644.
71.
YeXPierikFHHauserR. (2008) Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, The Netherlands: the Generation R study. Environmental Research108(2): 260–267.
72.
ZhouHChenDDunstanCR. (2008) Bone metabolism. In: OffermannsSRosenthalW (eds), Encyclopedia of Molecular Pharmacology. Berlin: Springer Heidelberg, pp. 276–283.
73.
ZiolkowskaARucinskiMPucherA. (2006) Expression of osteoblast marker genes in rat calvarial osteoblast-like cells, and effects of the endocrine disrupters diphenylolpropane, benzophenone-3, resveratrol and silymarin. Chemico-Biological Interactions164(3): 147–156.
