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Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain

Year 2018, Volume 37, Issue 2, 109 - 117, 15.10.2018
https://doi.org/10.30782/uluvfd.406938

Abstract

Summary

Bisphenol A (BPA) is a plasticizer found in reusable plastic containers, food and beverage cans, baby bottles and dental sealants. BPA exposure has become an important health concern based on its ability to “leach” from these products and penetrate the materials contained within them. Importantly, BPA can be transferred via placenta or lactation and this may affect the living body in intrauterine or lactation period.

Notch signaling pathway to regulate cell fate by modulating differentiation, proliferation, and survival of cells. It has been reported that the members of Notch signaling are expressed in brain. Notch1 is a member of Notch signalling pathway, that expresses in subventricular zone, choroid plexus, grey matter, white matter, hippocampus and cerebral vessels of brain.

In our study, we examined the effect of BPA on Notch1 expression in 5 different time intervals of fetal and neonatal periods in vivo.

Wistar rats were used in this study (n=60). Five different experimental and control groups were formed. The experimental groups were treated with BPA at 50 mg/kg/day when control groups were treated with sesame oil and ethanol at 9:1 (vehicle).

 During the first part of the experiment, BPA or vehicle was applied to three groups at E 18-21, P 0-3 and P 4-7 periods. When BPA or vehicle were injected intraperitoneally to pregnant dams in E 18-21 group neonatal pups in P0-3 and P4-7 groups were given  subcutaneous injections. The pups were sacrificed at the end of 7th day and their brain tissues were collected. During the second part of the experiment, similar applications with first experiment was performed. Following the application, pregnant dams were sacrificed and brain tissue of their fetuses were collected at E21stday and neonatal pups were sacrificed at P3rd day and their brains were collected.

Notch1 expression was assessed by using immunohistochemistry. Notch1 was expressed in the pia mater, the grey matter, around ventricles (ventricular walls and sub ventricular zone) and in choroid and vascular plexus of brain.

After BPA applications in fetal and neonatal periods, Notch1 expression was seen in different levels at E21st, P3rd and P7th days.

In conclusion, the effects of BPA on Notch1 immunohistochemical expression in brain tissue, varies depends on exposure time and the developmental period during the exposure.

References

  • Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science, 284: 770-776, 1999.
  • Berezovska O, McLean P, Knowles R, Frosh, M, Lu FM, Lux SE, Hyman BT. Notch1 inhibits neurite outgrowth in postmitotic primary neurons. Neuroscience, 9: 433-439,1999.
  • Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, Howdeshell KL, Zoeller RT, vom Saal F.S. Evaluating the effects of endocrine disruptors on endocrine function during development. Environ Health Persp, 107 Suppl 4: 613-618, 1999.
  • Brede C, Fjeldal P, Skjevrak I, Herikstad H. Increased migration levels of bisphenol A from polycarbonate baby bottles after dishwashing, boiling and brushing. Food Addit Contam, 20: 684-689, 2003.
  • Brotons JA, Olea-Serrano MF, Villalobos M, Pedraza V, Olea N. Xenoestrogens released from lacquer coatings in food cans. Environ Health Persp, 103: 608-12, 1995.
  • Calafat AM, Ye X, Wong Ly, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Persp, 116: 39-44, 2008.
  • Calafat AM, Weuve J, Ye X, Jia LT, Hu H, Ringer S, Huttner K, Hauser R. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Persp, 117: 639-44, 2009.
  • Carwile JL, Luu HT, Bassett LS, Driscoll DA, Yuan C, Chang, JY, Ye X, Calafat AM, Michels, KB. Polycarbonate bottle use and urinary bisphenol A concentrations. Environ Health Persp, 117: 1368-72, 2009.
  • Durmaz E, Giray BK. Çevresel bir endokrin bozucu: Bisfenol A ve toksik etkilerinin değerlendirilmesi. Çocuk Sağlığı ve Hastalıkları Dergisi, 56: 192-199, 2013.
  • Huang G, Cao X, Zhang X, Chang H, Yang Y, Du W, Wilson JX. Effects of soybean isoflavone on the notch signal pathway of the brain in rats with cerebral ischemia. J Nutr Sci Vitaminol (Tokyo), 55(4): 326-31, 2009.
  • Hunter NL, Susan M. Dymecki SM. Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus. Development, 134: 3449-3460, 2007.
  • Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod,17(11): 2839-41, 2002.
  • Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 283(5398): 70-74, 1999.
  • Irvin DK, Zurcher SD, Nguyen T,Weinmaster G, Kornblum HI. Expression Patterns of Notch1, Notch2, and Notch3 Suggest Multiple Functional Roles for the Notch-DSL Signaling System During Brain Development. J Comp Neurol, 436: 167-181, 2001.
  • Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell: 96, 25-34, 1999.
  • 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, 74: 2931-2940, 2004.
  • Koch U, Lehal R, Radtke F. Stem cells living with a Notch. Development, 140: 689-704, 2003.
  • Köktürk S, Alkan F, Dağistanlı F, Sezgin M, Uzunalan M, Uruluer B. Bromodeoksiuridin uygulamasını takiben erişkin sıçanbeyninde lateral ve üçüncü ventriküllerin ventriküler ve subventriküler zonunda mitojenik aktivitenin incelenmesi. Tıp Derg, 17(2): 77-80, 2007.
  • Lai EC. Notch signaling: control of cell communication and cell fate. Development, 131(5): 965-973, 2004.
  • McCarthy MM. Estradiol and the Developing Brain. Physiol Rev, 88(1): 91-124, 2008.
  • Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stemcells. Cell, 10: 499-510, 2000.
  • Oka T, Adati N, Shinkai T, Sakuma K, Nishimura T, Kurose K. Bisphenol A induces apoptosis in central neural cells during early development of Xenopus laevis. Biochem Bioph Res Co, 312(4): 877-882, 2003.
  • Olea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo-Fertrell A, Pedraza V, Soto AM, C. Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Persp, 104: 298-305, 1996.
  • Rubin BS, Lenkowski JR, Schaeberle CM, Vandenberg LN, Ronsheim PM, Soto AM. Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A. Endocrinology, 147: 3681-3691, 2006.
  • Safe SH, Pallaroni L, Yoon K, Gaido K, Ross S, Saville B, Donnell D.M. Toxicology of environmental estrogens. Reprod Fertil Dev, 13: 307-315, 2001.
  • Schönfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Persp, 110(11): A703-7, 2002.
  • Stump G, Durrer A, Klein AL, Lütolf S, Suter U, Verdon Taylor V. Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev, 114: 153-159, 2002.
  • Sun Y, Irie M, Kishikawa N, Wada M, Kuroda N, Nakashima K. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed Chromatogr, 18: 501-507, 2004.
  • Takahashi O ve Oishi S. Testicular toxicity of dietarily or parenterally administered bisphenol A in rats and mice. Food Chem Toxicol, 41(7): 1035-1044, 2003.
  • 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, 30: 75-95, 2009.
  • Vom Saal FS, Akingbemi BT, Belcher SM, Birnbaum LS, Crain DA, Eriksen M, Farabollini F, Guillette Jr LJ, Hauser R, Heindel JJ, Ho SM, Hunt PA, Iguchi T, Jobling S, Kanno J, Keri RA, Karen E. Knudsen KE, Laufer H, Leblanc G.A, Marcus M, Mclachlan JA, Myers JP, Nadal A, Newbold RR Olea N, Prins, G.S., Richter CA, Rubin BS, Sonnenschein C, Soto AM, Talsness C.E, Vandenbergh JG, Vandenberg LN, Walser-Kuntz DR, Watson CS, Welshons WV, Yelena Wetherill Y, Zoeller RT. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol, 24: 131-138, 2007.
  • Yang X, Klein R, Tian X, Cheng HT, Kopan R, Shen J. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol, 269(1): 81-94, 2004.
  • Yoo SD, Shin BS, Lee BM, Lee KC, Han SY, Kim HS, Kwack SJ, Park KL. Bioavailability and mammary excretion of bisphenol a in sprague-dawley rats. J. Toxicol Env Heal A, 64: 417-426, 2001.

Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain

Year 2018, Volume 37, Issue 2, 109 - 117, 15.10.2018
https://doi.org/10.30782/uluvfd.406938

Abstract

Summary

Bisphenol A (BPA) is a plasticizer found in reusable plastic containers, food and beverage cans, baby bottles and dental sealants. BPA exposure has become an important health concern based on its ability to “leach” from these products and penetrate the materials contained within them. Importantly, BPA can be transferred via placenta or lactation and this may affect the living body in intrauterine or lactation period.

Notch signaling pathway to regulate cell fate by modulating differentiation, proliferation, and survival of cells. It has been reported that the members of Notch signaling are expressed in brain. Notch1 is a member of Notch signalling pathway, that expresses in subventricular zone, choroid plexus, grey matter, white matter, hippocampus and cerebral vessels of brain.

In our study, we examined the effect of BPA on Notch1 expression in 5 different time intervals of fetal and neonatal periods in vivo.

Wistar rats were used in this study (n=60). Five different experimental and control groups were formed. The experimental groups were treated with BPA at 50 mg/kg/day when control groups were treated with sesame oil and ethanol at 9:1 (vehicle).

 During the first part of the experiment, BPA or vehicle was applied to three groups at E 18-21, P 0-3 and P 4-7 periods. When BPA or vehicle were injected intraperitoneally to pregnant dams in E 18-21 group neonatal pups in P0-3 and P4-7 groups were given  subcutaneous injections. The pups were sacrificed at the end of 7th day and their brain tissues were collected. During the second part of the experiment, similar applications with first experiment was performed. Following the application, pregnant dams were sacrificed and brain tissue of their fetuses were collected at E21stday and neonatal pups were sacrificed at P3rd day and their brains were collected.

Notch1 expression was assessed by using immunohistochemistry. Notch1 was expressed in the pia mater, the grey matter, around ventricles (ventricular walls and sub ventricular zone) and in choroid and vascular plexus of brain.

After BPA applications in fetal and neonatal periods, Notch1 expression was seen in different levels at E21st, P3rd and P7th days.

In conclusion, the effects of BPA on Notch1 immunohistochemical expression in brain tissue, varies depends on exposure time and the developmental period during the exposure.

References

  • Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science, 284: 770-776, 1999.
  • Berezovska O, McLean P, Knowles R, Frosh, M, Lu FM, Lux SE, Hyman BT. Notch1 inhibits neurite outgrowth in postmitotic primary neurons. Neuroscience, 9: 433-439,1999.
  • Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, Howdeshell KL, Zoeller RT, vom Saal F.S. Evaluating the effects of endocrine disruptors on endocrine function during development. Environ Health Persp, 107 Suppl 4: 613-618, 1999.
  • Brede C, Fjeldal P, Skjevrak I, Herikstad H. Increased migration levels of bisphenol A from polycarbonate baby bottles after dishwashing, boiling and brushing. Food Addit Contam, 20: 684-689, 2003.
  • Brotons JA, Olea-Serrano MF, Villalobos M, Pedraza V, Olea N. Xenoestrogens released from lacquer coatings in food cans. Environ Health Persp, 103: 608-12, 1995.
  • Calafat AM, Ye X, Wong Ly, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Persp, 116: 39-44, 2008.
  • Calafat AM, Weuve J, Ye X, Jia LT, Hu H, Ringer S, Huttner K, Hauser R. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Persp, 117: 639-44, 2009.
  • Carwile JL, Luu HT, Bassett LS, Driscoll DA, Yuan C, Chang, JY, Ye X, Calafat AM, Michels, KB. Polycarbonate bottle use and urinary bisphenol A concentrations. Environ Health Persp, 117: 1368-72, 2009.
  • Durmaz E, Giray BK. Çevresel bir endokrin bozucu: Bisfenol A ve toksik etkilerinin değerlendirilmesi. Çocuk Sağlığı ve Hastalıkları Dergisi, 56: 192-199, 2013.
  • Huang G, Cao X, Zhang X, Chang H, Yang Y, Du W, Wilson JX. Effects of soybean isoflavone on the notch signal pathway of the brain in rats with cerebral ischemia. J Nutr Sci Vitaminol (Tokyo), 55(4): 326-31, 2009.
  • Hunter NL, Susan M. Dymecki SM. Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus. Development, 134: 3449-3460, 2007.
  • Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod,17(11): 2839-41, 2002.
  • Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 283(5398): 70-74, 1999.
  • Irvin DK, Zurcher SD, Nguyen T,Weinmaster G, Kornblum HI. Expression Patterns of Notch1, Notch2, and Notch3 Suggest Multiple Functional Roles for the Notch-DSL Signaling System During Brain Development. J Comp Neurol, 436: 167-181, 2001.
  • Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell: 96, 25-34, 1999.
  • 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, 74: 2931-2940, 2004.
  • Koch U, Lehal R, Radtke F. Stem cells living with a Notch. Development, 140: 689-704, 2003.
  • Köktürk S, Alkan F, Dağistanlı F, Sezgin M, Uzunalan M, Uruluer B. Bromodeoksiuridin uygulamasını takiben erişkin sıçanbeyninde lateral ve üçüncü ventriküllerin ventriküler ve subventriküler zonunda mitojenik aktivitenin incelenmesi. Tıp Derg, 17(2): 77-80, 2007.
  • Lai EC. Notch signaling: control of cell communication and cell fate. Development, 131(5): 965-973, 2004.
  • McCarthy MM. Estradiol and the Developing Brain. Physiol Rev, 88(1): 91-124, 2008.
  • Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stemcells. Cell, 10: 499-510, 2000.
  • Oka T, Adati N, Shinkai T, Sakuma K, Nishimura T, Kurose K. Bisphenol A induces apoptosis in central neural cells during early development of Xenopus laevis. Biochem Bioph Res Co, 312(4): 877-882, 2003.
  • Olea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo-Fertrell A, Pedraza V, Soto AM, C. Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Persp, 104: 298-305, 1996.
  • Rubin BS, Lenkowski JR, Schaeberle CM, Vandenberg LN, Ronsheim PM, Soto AM. Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A. Endocrinology, 147: 3681-3691, 2006.
  • Safe SH, Pallaroni L, Yoon K, Gaido K, Ross S, Saville B, Donnell D.M. Toxicology of environmental estrogens. Reprod Fertil Dev, 13: 307-315, 2001.
  • Schönfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Persp, 110(11): A703-7, 2002.
  • Stump G, Durrer A, Klein AL, Lütolf S, Suter U, Verdon Taylor V. Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev, 114: 153-159, 2002.
  • Sun Y, Irie M, Kishikawa N, Wada M, Kuroda N, Nakashima K. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed Chromatogr, 18: 501-507, 2004.
  • Takahashi O ve Oishi S. Testicular toxicity of dietarily or parenterally administered bisphenol A in rats and mice. Food Chem Toxicol, 41(7): 1035-1044, 2003.
  • 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, 30: 75-95, 2009.
  • Vom Saal FS, Akingbemi BT, Belcher SM, Birnbaum LS, Crain DA, Eriksen M, Farabollini F, Guillette Jr LJ, Hauser R, Heindel JJ, Ho SM, Hunt PA, Iguchi T, Jobling S, Kanno J, Keri RA, Karen E. Knudsen KE, Laufer H, Leblanc G.A, Marcus M, Mclachlan JA, Myers JP, Nadal A, Newbold RR Olea N, Prins, G.S., Richter CA, Rubin BS, Sonnenschein C, Soto AM, Talsness C.E, Vandenbergh JG, Vandenberg LN, Walser-Kuntz DR, Watson CS, Welshons WV, Yelena Wetherill Y, Zoeller RT. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol, 24: 131-138, 2007.
  • Yang X, Klein R, Tian X, Cheng HT, Kopan R, Shen J. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol, 269(1): 81-94, 2004.
  • Yoo SD, Shin BS, Lee BM, Lee KC, Han SY, Kim HS, Kwack SJ, Park KL. Bioavailability and mammary excretion of bisphenol a in sprague-dawley rats. J. Toxicol Env Heal A, 64: 417-426, 2001.

Details

Primary Language English
Subjects Science
Journal Section Articles
Authors

Özlem ÖZDEN AKKAYA>
Afyon Kocatepe Üniversitesi, Veteriner Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı
Türkiye


Artay Yağcı>
Afyon Kocatepe Üniversitesi, Veteriner Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı
Türkiye


Murat Tosun>
Afyon Kocatepe Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı
0000-0001-9673-9771
Türkiye


Korhan ALTUNBAŞ> (Primary Author)
Afyon Kocatepe Üniversitesi, Veteriner Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı
Türkiye

Publication Date October 15, 2018
Published in Issue Year 2018, Volume 37, Issue 2

Cite

Bibtex @research article { uluvfd406938, journal = {Uludağ Üniversitesi Veteriner Fakültesi Dergisi}, issn = {1301-3173}, address = {}, publisher = {Bursa Uludağ University}, year = {2018}, volume = {37}, number = {2}, pages = {109 - 117}, doi = {10.30782/uluvfd.406938}, title = {Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain}, key = {cite}, author = {Özden Akkaya, Özlem and Yağcı, Artay and Tosun, Murat and Altunbaş, Korhan} }
APA Özden Akkaya, Ö. , Yağcı, A. , Tosun, M. & Altunbaş, K. (2018). Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain . Uludağ Üniversitesi Veteriner Fakültesi Dergisi , 37 (2) , 109-117 . DOI: 10.30782/uluvfd.406938
MLA Özden Akkaya, Ö. , Yağcı, A. , Tosun, M. , Altunbaş, K. "Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain" . Uludağ Üniversitesi Veteriner Fakültesi Dergisi 37 (2018 ): 109-117 <https://dergipark.org.tr/en/pub/uluvfd/issue/37089/406938>
Chicago Özden Akkaya, Ö. , Yağcı, A. , Tosun, M. , Altunbaş, K. "Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain". Uludağ Üniversitesi Veteriner Fakültesi Dergisi 37 (2018 ): 109-117
RIS TY - JOUR T1 - Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain AU - Özlem Özden Akkaya , Artay Yağcı , Murat Tosun , Korhan Altunbaş Y1 - 2018 PY - 2018 N1 - doi: 10.30782/uluvfd.406938 DO - 10.30782/uluvfd.406938 T2 - Uludağ Üniversitesi Veteriner Fakültesi Dergisi JF - Journal JO - JOR SP - 109 EP - 117 VL - 37 IS - 2 SN - 1301-3173- M3 - doi: 10.30782/uluvfd.406938 UR - https://doi.org/10.30782/uluvfd.406938 Y2 - 2018 ER -
EndNote %0 Uludag University Journal of the Faculty of Veterinary Medicine Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain %A Özlem Özden Akkaya , Artay Yağcı , Murat Tosun , Korhan Altunbaş %T Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain %D 2018 %J Uludağ Üniversitesi Veteriner Fakültesi Dergisi %P 1301-3173- %V 37 %N 2 %R doi: 10.30782/uluvfd.406938 %U 10.30782/uluvfd.406938
ISNAD Özden Akkaya, Özlem , Yağcı, Artay , Tosun, Murat , Altunbaş, Korhan . "Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain". Uludağ Üniversitesi Veteriner Fakültesi Dergisi 37 / 2 (October 2018): 109-117 . https://doi.org/10.30782/uluvfd.406938
AMA Özden Akkaya Ö. , Yağcı A. , Tosun M. , Altunbaş K. Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain. Uludağ Üniversitesi Veteriner Fakültesi Dergisi. 2018; 37(2): 109-117.
Vancouver Özden Akkaya Ö. , Yağcı A. , Tosun M. , Altunbaş K. Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain. Uludağ Üniversitesi Veteriner Fakültesi Dergisi. 2018; 37(2): 109-117.
IEEE Ö. Özden Akkaya , A. Yağcı , M. Tosun and K. Altunbaş , "Effects of BPA on Notch1 Immunohistochemical Expression in Fetal and Neonatal Rat Brain", Uludağ Üniversitesi Veteriner Fakültesi Dergisi, vol. 37, no. 2, pp. 109-117, Oct. 2018, doi:10.30782/uluvfd.406938