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Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

Part of: DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  16 July 2019

Jakeline Liara Teleken ,
Ellen Carolina Zawoski Gomes ,
Carine Marmentini ,
Milara Bruna Moi ,
Rosane Aparecida Ribeiro ,
Sandra Lucinei Balbo ,
Elaine Manoela Porto Amorim  and
Maria Lúcia Bonfleur Open the ORCID record for Maria Lúcia Bonfleur [Opens in a new window]
Jakeline Liara Teleken
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Ellen Carolina Zawoski Gomes
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Carine Marmentini
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Milara Bruna Moi
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Rosane Aparecida Ribeiro
Affiliation:
Laboratório Integrado de Morfologia, NUPEM, Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Macaé, RJ, Brazil
Sandra Lucinei Balbo
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Elaine Manoela Porto Amorim
Affiliation:
Laboratório de Histologia, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
Maria Lúcia Bonfleur*
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
*
Address for correspondence: Maria Lúcia Bonfleur, Laboratório de Fisiologia Endócrina e Metabolismo, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, CEP 85819-110, Brazil. Email: [email protected]
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Abstract

One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus–pituitary–testicular axis regulation in F1 offspring.

Keywords

Developmental origins of health and diseaseendocrine disruptor chemicalhypothalamus–pituitary–testicular axispesticidesspermatozoatestosterone
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 2 , April 2020 , pp. 146 - 153
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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References

Londres, F. AGROTÓXICOS NO BRASIL Um Guia Para Ação Em Defesa Da Vida, 2011. Rio de Janeiro: AS-PTA – Assessoria e Serviços à Projetos em Agricultura Alternativa, p. 190.Google Scholar
The World Health Organization (WHO). Exposure To Highly Hazardous Pesticides: A Major Public Health Concern. 2010. https://www.who.int/ipcs/features/hazardous_pesticides.pdf?ua=1 (accessed 23 September 2018).Google Scholar
De, A, Bose, R, Kumar, A, Mozumdar, S.Targeted Delivery of Pesticides Using Biodegradable Polymeric Nanoparticles, 2014. Springer Briefs in Molecular Science, pp. 5–6.CrossRefGoogle Scholar
Acquavella, JF, Alexander, BH, Mandel, JS, Gustin, C, Baker, B, Chapman, P.Glyphosate biomonitoring for farmers and their families: results from the farm family exposure study. Environ Health Perspect. 2004; 112, 321–326.CrossRefGoogle ScholarPubMed
Bai, SH, Ogbourne, SM.Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res. 2016; 23, 18988–19001.CrossRefGoogle ScholarPubMed
Duke, SO, Powles, SB.Glyphosate: a once-in-a-century herbicide. Pest Manag Sci. 2008; 64, 319–325.CrossRefGoogle ScholarPubMed
AGROFIT: Sistema de Agrotóxicos Fitossanitários. Ministério da Agricultura Pecuária e Abastecimento.Google Scholar
Dill, GM, Sammons, RD, Feng, PCC, et al.Glyphosate: Discovery, Development, Applications, and Properties, in: Nandula, VK, (Ed), Glyphosate Resistence in Crops Weeds: History, Development, and Management. 2010, Hoboken: John Wiley & Sons, Inc, pp. 1–33.Google Scholar
Williams, GM, Kroes, R, Munro, IC.Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol. 2000; 31, 117–165.CrossRefGoogle ScholarPubMed
Cattani, D, Cesconetto, PA, Tavares, MK, et al.Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: implication of glutamate excitotoxicity and oxidative stress. Toxicology. 2017; 387, 67–80.CrossRefGoogle ScholarPubMed
Good, P.Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup). Clin Nutr ESPEN. 2018; 23, 171–183.CrossRefGoogle Scholar
Romano, RM, Romano, MA, Bernardi, MM, Furtado, PV, Oliveira, CA.Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Arch Toxicol. 2010; 84, 309–317.CrossRefGoogle ScholarPubMed
Beuret, CJ, Zirulnik, F, Giménez, MS.Effect of the herbicide glyphosate on liver lipoperoxidation in pregnant rats and their fetuses. Reprod Toxicol. 2005; 19, 501–504.CrossRefGoogle ScholarPubMed
Gallegos, CE, Bartos, M, Bras, C, Gumilar, F, Antonelli, MC, Minetti, A.Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring. Neurotoxicology. 2016; 53, 20–28.CrossRefGoogle ScholarPubMed
de Souza, JS, Kizys, MML, da Conceição, RR, et al.Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats. Toxicology. 2017; 377, 25–37.CrossRefGoogle ScholarPubMed
Dallegrave, E, Mantese, FD, Oliveira, RT, Andrade, AJM, Dalsenter, PR, Langeloh, A.Pre- and postnatal toxicity of the commercial glyphosate formulation in Wistar rats. Arch Toxicol. 2007; 81, 665–673.CrossRefGoogle ScholarPubMed
Romano, MA, Wisniewski, P, Viau, P, et al.Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression. Arch Toxicol. 2012; 86, 663–673.CrossRefGoogle ScholarPubMed
Pandey, A, Rudraiah, M. Analysis of endocrine disruption effect of Roundup® in adrenal gland of male rats. 2015; 2, 1075–1085.Google Scholar
Padmanabhan, V, Cardoso, RC, Puttabyatappa, M.Developmental programming, a pathway to disease. Endocrinology. 2016; 157, 1328–1340.CrossRefGoogle ScholarPubMed
Bergman, Å, Heindel, J, Jobling, S, Kidd, K, Zoeller, RT.State of the Science of Endocrine Disrupting Chemicals, 2012, 2012; Vol. 211.CrossRefGoogle Scholar
Agarwal, P, Morriseau, TS, Kereliuk, SM, et al.Critical reviews in clinical laboratory sciences maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring. Crit Rev Clin Lab Sci. 2018; 55, 71–101.CrossRefGoogle ScholarPubMed
de Gusmão Correia, ML, Volpato, AM, Águila, MB, Mandarim-de-Lacerda, CA. Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome. J Hum Hypertens. 2012; 26, 405–419.CrossRefGoogle ScholarPubMed
Hales, CN, Barker, DJP.Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. 1992. Int J Epidemiol. 2013; 42, 1215–1222.CrossRefGoogle ScholarPubMed
Barker, DJP.The origins of the developmental origins theory. J Intern Med. 2007; 261, 412–417.CrossRefGoogle ScholarPubMed
Ho, S-M, Cheong, A, Adgent, MA, et al.Environmental factors, epigenetics, and developmental origin of reproductive disorders HHS public access. Reprod Toxicol. 2017; 68, 85–104.CrossRefGoogle Scholar
Chadio, S, Kotsampasi, B.The role of early life nutrition in programming of reproductive function. J Dev Orig Health Dis. 2014; 5, 2–15.CrossRefGoogle ScholarPubMed
Valli, H, Phillips, BT, Orwig, KE, Gassei, K, Nagano, MC.Spermatogenesis, in: Knobil and Neill’s Physiology of Reproduction. 2015. Elsevier Inc, pp. 595–635.CrossRefGoogle Scholar
Robaire, B, Hinton, BT.The epididymis. In: Knobil and Neill’s Physiology of Reproduction. 2015; Elsevier Inc, pp. 691–771.CrossRefGoogle Scholar
Pham, TH, Derian, L, Kervarrec, C, et al.Perinatal exposure to glyphosate and a glyphosate-based herbicide affect spermatogenesis in mice. Toxicol Sci. 2019; 169, 260–271.CrossRefGoogle Scholar
Daruich, J, Zirulnik, F, Sofía Gimenez, M.Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses. Environ Res. 2001; 85, 226–231.CrossRefGoogle ScholarPubMed
Cassault-Meyer, E, Gress, S, Séralini, GÉ, Galeraud-Denis, I.An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality. Environ Toxicol Pharmacol. 2014; 38, 131–140.CrossRefGoogle ScholarPubMed
Bali, YA, Kaikai, N, Ba-M’hamed, S, Bennis, M.Learning and memory impairments associated to acetylcholinesterase inhibition and oxidative stress following glyphosate based-herbicide exposure in mice. Toxicology. 2019; 415, 18–25.CrossRefGoogle ScholarPubMed
EPA, Environmental Protection Agency. Registration Eligibility Decision Document Glyphosate. 1993.Google Scholar
Marques, RM, Oshio, LT. Em Roedores. 2009, 36001.Google Scholar
Sarkar, D, Singh, SK.Inhibition of testicular steroidogenesis and impaired differentiation of Sertoli cells in peripubertal mice o ff spring following maternal exposure to BDE-209 during lactation suppress germ cell proliferation. Toxicol Lett. 2018; 290, 83–96.CrossRefGoogle Scholar
Jeyaraj, DA, Grossman, G, Petrusz, P.Altered bioavailability of testosterone in androgen-binding protein-transgenic mice. Steroids. 2005; 70, 704–714.CrossRefGoogle ScholarPubMed
R CORE TEAM. R: A Language and Environment for Statistical Computing, 2015. R Foundation for Statistical Computing.Google Scholar
Haugen, AC, Schug, TT, Collman, G, Heindel, JJ.Evolution of DOHaD: the impact of enviromental health sciences. J Dev Orig Helath Dis. 2015; 6, 55–64.CrossRefGoogle Scholar
Vandenberg, LN, Blumberg, B, Antoniou, MN, et al.Is it time to reassess current safety standards for glyphosate-based herbicides?. J Epidemiol Community Health. 2017; 71, 613–618.CrossRefGoogle ScholarPubMed
Defarge, N, Takács, E, Lozano, VL, et al.Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels. Int J Environ Res Public Health. 2016; 13, 264.CrossRefGoogle ScholarPubMed
Mesnage, R, Defarge, N, Spiroux De Vendômois, J, Séralini, GE.Major pesticides are more toxic to human cells than their declared active principles. Biomed Res Int. 2014; 2014, 179691.CrossRefGoogle ScholarPubMed
Chłopecka, M, Mendel, M, Dziekan, N, Karlik, W.The effect of glyphosate-based herbicide Roundup and its co-formulant, POEA, on the motoric activity of rat intestine – In vitro study. Environ Toxicol Pharmacol. 2017; 49, 156–162.CrossRefGoogle ScholarPubMed
Ruhlen, RL, Taylor, JA, Mao, J, Kirkpatrick, J, Welshons, WV, Saal, FS. Choice of animal feed can alter fetal steroid levels and mask developmental effects of endocrine disrupting chemicals. 2011; 2, 36–48.Google Scholar
Parvez, S, Gerona, RR, Proctor, C, et al.Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study. J Dev Orig Helath Dis. 2018; 2, 1–12.Google Scholar
Tang, J, Hu, P, Li, Y, Li, C.Ion imbalance is involved in the mechanisms of liver oxidative damage in rats exposed to glyphosate. Front Physiol. 2017; 8, 1–12.CrossRefGoogle ScholarPubMed
Hughes, IA, Acerini, CL.Factors controlling testis descent. Eur J Endocrinol. 2008; 159, 75–82CrossRefGoogle ScholarPubMed
Toppari, J, Virtanen, H, Skakkebaek, NE, Main, KM. Environmental effects on hormonal regulation of testicular descent. 2006; 102, 184–186.Google Scholar
Colciago, A, Casati, L, Mornati, O, et al.Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat Part 2: effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring. Toxicol Appl Pharmacol. 2009; 239, 46–54.CrossRefGoogle ScholarPubMed
Fénichel, P, Chevalier, N, Lahlou, N, et al.Endocrine disrupting chemicals interfere with Leydig Cell Hormone pathways during testicular descent in idiopathic cryptorchidism. Front Endocrinol. 2019; 9, 1–8.CrossRefGoogle ScholarPubMed
Jin, J, Yang, W.Molecular regulation of hypothalamus – pituitary – gonads axis in males. Gene. 2014; 551, 15–25.CrossRefGoogle ScholarPubMed
Clarkson, J, Herbison, AE, Clarkson, J.Hypothalamic control of the male neonatal testosterone surge. Philos Trans R Soc Lond B Biol Sci. 2016; 371, 20150115.CrossRefGoogle ScholarPubMed
Lenz, KM, Mccarthy, MM.Organized for sex-steroid hormones and the developing hypothalamus. Eur J Neurosci.2017; 32, 2096–2104.CrossRefGoogle Scholar
Benachour, N, Sipahutar, H, Moslemi, S, Gasnier, C, Travert, C, Séralini, GE.Time- and dose-dependent effects of roundup on human embryonic and placental cells. Arch Environ Contam Toxicol. 2007; 53, 126–133.CrossRefGoogle ScholarPubMed
Walker, WH.Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis. 2011; 1, 116–120.CrossRefGoogle ScholarPubMed
Gasnier, C, Dumont, C, Benachour, N, Clair, E, Chagnon, MC, Séralini, GE.Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology. 2009; 262, 184–191.CrossRefGoogle ScholarPubMed
Gregory, SJ, Kaiser, UB.Regulation of gonadotropins by inhibin and activin. Semin Reprod Med. 2004; 22, 253–267.CrossRefGoogle ScholarPubMed