Animal Reproduction (AR)
https://www.animal-reproduction.org/article/doi/10.21451/1984-3143-2017-AR960
Animal Reproduction (AR)
Original Article

Simazine, a triazine herbicide, disrupts swine granulosa cell functions

Francesca Grasselli; Simona Bussolati; Roberto Ramoni; Stefano Grolli; Giuseppina Basini

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Abstract

The triazine herbicide simazine is a pesticide commonly detected in surface and ground waters, although banned in most European countries since 2004. Concerns for humans and animal health result from its potential endocrine disrupting action, that can lead to reproductive disorders. The present in vitro study was undertaken to study simazine effects on swine granulosa cell function, namely cell viability, proliferation, steroidogenesis and NO production. Moreover, the ability of this substance to interfere with the angiogenetic process, a crucial event in reproductive function, was taken into account. Our data document that simazine treatment, at 0.1 or 10 μM concentration levels, stimulates granulosa cell proliferation and viability and impairs steroidogenesis, increasing in particular progesterone production. In addition, the in vitro angiogenesis bioassay revealed a significant simazine stimulatory effect on immortalized porcine Aortic Endothelial Cell proliferation. Collectively, these results show that simazine can display disruptive effects on ovarian cell functional parameters, possibly resulting in reproductive dysfunction. This hypothesis is also supported by the observed pro-angiogenetic properties of this herbicide, as already suggested for different endocrine disruptors.

Keywords

simazine, endocrine disruptor, swine granulosa cells, ovarian function, angiogenesis

References

Basini G , Bussolati S , Santini S , Bianchi F , Careri M , Mangia A , Musci M , Grasselli F. 2008 . Hydroxyestrogens inhibit angiogenesis in swine ovarian follicles . J Endocrinol , 199 : 127 - 135 .

Basini G , Bianchi F , Bussolati S , Baioni L , Ramoni R , Grolli S , Conti V , Bianchi F , Grasselli F. 2012 . Atrazine disrupts steroidogenesis, VEGF and NO production in swine granulosa cells . Ecotoxicol Environ Saf , 85 : 59 - 63 .

Basini G , Tamanini C. 2000 . Selenium stimulates estradiol production in bovine granulosa cells: possible involvement of nitric oxide . Domest Anim Endocrinol , 18 ( 1 ): 1 - 17 .

Basini G , Bussolati S , Grolli S , Ramoni R , Grasselli F. 2016 . Bisphenol A interferes with swine vascular endothelial cell functions . Can J Physiol Pharmacol , 20 : 1 - 7 .

Bexfield LM . 2008 . Decadal-scale changes of pesticides in ground water of the United States, 1993-2003 . J Environ Qual , 37 ( Suppl.5 ): S226 - 39 .

Breckenridge CB , Campbell JL , Clewell HJ , Andersen ME , Valdez-Flores C , Sielken RL Jr . 2016 . PBPK-based Probabilistic Risk Assessment for Total Chlorotriazines in Drinking Water . Toxicol Sci , 150 ( 2 ): 269 - 282 .

Commission of the European Communities . 2004 a . Commission Decision of 10 March 2004 concerning the non-inclusion of simazine in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance (2004/247/EC). Off J Eur Union , L78 : 50 - 52 .

Commission of the European Communities . 2004 b . Commission Decision of 10 March 2004 concerning the non-inclusion of atrazine in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing this active substance (2004/248/EC). Off J Eur Union , L78 : 53 - 55 .

Cooper RL , Stoker TE , Tyrey L , Goldman JM , McElroy WK . 2000 . Atrazine disrupts the hypothalamic control of pituitary-ovarian function . Toxicol Sci , 53 ( 2 ): 297 - 307 .

Cooper RL , Laws SC , Das PC , Narotsky MG , Goldman JM , Lee Tyrey E , Stoker TE . 2007 . Atrazine and reproductive function: mode and mechanism of action studies . Birth Defects Res B Dev Reprod Toxico , 80 ( 2 ): 98 - 112 .

Dong YL , Yallampalli C . 1996 . Interaction between nitric oxide and prostaglandin E2 pathways in pregnant rat uteri . Am J Physiol , 270 ( 3 Pt 1 ): E471 - 6 .

Durando M , Kass L , Perdomo V , Bosquiazzo VL , Luque EH , Muñoz-de-Toro M . 2011 . Prenatal exposure to bisphenol A promotes angiogenesis and alters steroid-mediated responses in the mammary glands of cycling rats . J Steroid Biochem Mol Biol , 1 27 ( 1-2 ): 35 - 43 .

European Parliament and Council of the European Union . 2001 . Decision No 2455/2001/EC of the European Parliament and of the Council of 20 November 2001 establishing the list of priority substances in the field of water policy and amending Directive 2000/60/EC . Off J Eur Communities , L331 : 0001 - 0005 .

Fa S , Pogrmic-Majkic K , Samardzija D , Glisic B , Kaisarevic S , Kovacevic R , Andric N. 2013 . Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells . Toxicol Appl Pharmacol , 270 ( 1 ): 1 - 8 .

Fan W , Yanase T , Morinaga H , Gondo S , Okabe T , Nomura M , Komatsu T , Morohashi K , Hayes TB , Takayanagi R , Nawata H . 2007 . Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans . Environ Health Perspect , 115 ( 5 ): 720 - 727 .

Forgacs AL , D'Souza ML , Huhtaniemi IT , Rahman NA , Zacharewski TR . 2013 . Triazine herbicides and their chlorometabolites alter steroidogenesis in BLTK1 murine Leydig cells . Toxicol Sci , 134 ( 1 ): 155 - 167 .

Fuhrman BJ , Schairer C , Gail MH , Boyd-Morin J , Xu X , Sue LY , Buys SS , Isaacs C , Keefer LK , Veenstra TD , Berg CD , Hoover RN , Ziegler RG . 2012 . Estrogen metabolism and risk of breast cancer in postmenopausal women . J Natl Cancer Inst , 104 ( 4 ): 326 - 339 .

Grasselli F , Basini G , Tirelli M , Cavalli V , Bussolati S , Tamanini C. 2003 . Angiogenic activity of porcine granulosa cells co-cultured with endothelial cells in a microcarrier-based three-dimensional fibrin gel . J Physiol Pharmacol , 54 : 361 - 370 .

Grasselli F , Baratta M , Tamanini C. 1993 . Effects of a GnRH analogue (buserelin) infused via osmotic minipumps on pituitary and ovarian activity of prepuberal heifers . Anim Reprod , 32 : 153 - 161 .

Grasselli F , Baratta L , Baioni L , Bussolati S , Ramoni R , Grolli S , Basini G. 2010 . Bisphenol A disrupts granulosa cell function . Domest Anim Endocrinol , 39 ( 1 ): 34 - 39 .

Hu K , Tian Y , Du Y , Huang L , Chen J , Li N , Liu W , Liang Z , Zhao L. 2016 . Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling . Int J Oncol , 48 ( 5 ): 2166 - 2174 .

Istituto Superiore per la Protezione e la Ricerca Ambientale ( ISPRA ). 2016 . Rapporto nazionale pesticidi nelle acque . Available in: http://www.isprambiente.gov.it .

Loos R , Locoro G , Comero S , Contini S , Schwesig D , Werres F , Balsaa P , Gans O , Weiss S , Blaha L , Bolchi M , Gawlik BM . 2010 . Pan-European survey on the occurrence of selected polar organic persistent pollutants in ground water . Water Res , 44 : 4115 - 4126 .

Park S , Kim S , Jin H , Lee K , Bae J. 2014 . Impaired development of female mouse offspring maternally exposed to simazine . Environ Toxicol Pharmacol , 38 ( 3 ): 845 - 51 .

Park SE , Lim SR , Choi HK , Bae J . 2016 . Triazine herbicides inhibit relaxin signaling and disrupt nitric oxide homeostasis . Toxicol Appl Pharmacol , 15 , 307 : 10 - 8 .

Pogrmic-Majkic K , Fa S , Samardzija D , Hrubik J , Kaisarevic S , Andric N . 2016 . Atrazine activates multiple signaling pathways enhancing the rapid hCG-induced androgenesis in rat Leydig cells . Toxicology , 10 , 368-369 : 37 - 45 .

Qian HF , Takuma T , Tsuyoshi E , Fumihiko S . 2014 . The PGR5 and NDH pathways in photosynthetic cyclic electron transfer respond differently to sub-lethal treatment with photosystem-interfering herbicides . J Agric Food Chem , 62 : 4083 - 4089 .

Ren R , Sun DJ , Yan H , Wu YP , Zhang Y . 2013 . Oral exposure to the herbicide simazine induces mouse spleen immunotoxicity and immune cell apoptosis . Toxicol Pathol , 1 ( 1 ): 63 - 72 .

Rich JD , Gabriel SM , Schultz-Norton JR . 2012 . In vitro effects of herbicides and insecticides on human breast cells . ISRN Toxicol , 14 : 232461 .

Sai L , Liu Y , Qu B , Yu G , Guo Q , Bo C , Xie L , Jia Q , Li Y , Li X , Ng JC , Peng C . 2015 . The Effects of Simazine, a Chlorotriazine Herbicide, on the Expression of Genes in Developing MaleXenopus laevis . Bull Environ Contam Toxicol , 95 ( 2 ): 157 - 63 .

Sanderson JT , Letcher RJ , Heneweer M , Giesy JP , van den Berg M . 2001 . Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes . Environ Health Perspect , 109 ( 10 ): 1027 - 31 .

Sassine L , Le Gal La Salle C , Khaska M , Verdoux P , Meffre P , Benfodda Z , Roig B. 2016 . Spatial distribution of triazine residues in a shallow alluvial aquifer linked to groundwater residence time . Environ Sci Pollut Res Int , ( 8 ): 6878 - 6888 . Doi: [https://doi.org/10.1007/s11356-016-7224-x] .

Stara A , Machova J , Velisek J. 2012 . Effect of chronic exposure to simazine on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.) . Environ Toxicol Pharmacol , 33 ( 2 ): 334 - 43 .

Stevens JT , Breckenridge CB , Wetzel LT , Gillis JH , Luempert LG 3rd , Eldridge JC . 1994 . Hypothesis for mammary tumorigenesis in Sprague-Dawley rats exposed to certain triazine herbicides . J Toxicol Environ Health , 43 ( 2 ): 139 - 53 .

Thurman EM , Goolsby DA , Meyer MT , Mills MS , Pomes ML , Kolpin DW . 1992 . A reconnaissance study of herbicides and their metabolites in surface water of the Midwestern United States using immunoassay and gas chromatography/mass spectrometry . Environ Sci Tech , 26 : 2440 - 2447 .

Tinfo NS , Hotchkiss MG , Buckalew AR , Zorrilla LM , Cooper RL , Laws SC . 2011 . Understanding the effects of atrazine on steroidogenesis in rat granulosa and H295R adrenal cortical carcinoma cells . Reprod Toxicol , 31 ( 2 ): 184 - 193 .

United States Environmental Protection Agency (USEPA) . 2006 . Triazine Cumulative Risk Assessment . Office of Prevention, Pesticides and Toxic Substances , Washington, DC . Federal Register March , 2006 , pp. 1 - 65 .

Zorrilla LM , Gibson EK , Stoker TE . 2010 . The effects of simazine, a chlorotriazine herbicide, on pubertal development in the female Wistar rat . Reprod Toxicol , 29 ( 4 ): 393 - 400 .

 

 

 

 

 

 

 

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