Advertisement

Archives of Toxicology

, Volume 92, Issue 8, pp 2629–2643 | Cite as

Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats

  • María M. Milesi
  • Virginia Lorenz
  • Guillermina Pacini
  • María R. Repetti
  • Luisina D. Demonte
  • Jorgelina Varayoud
  • Enrique H. Luque
Reproductive Toxicology

Abstract

Glyphosate-based herbicides (GBHs) are the most globally used herbicides raising the risk of environmental exposition. Here, we investigated whether perinatal exposure to low doses of a GBH alters the female reproductive performance, and/or induced second-generation effects related to congenital anomalies or growth alterations. Pregnant rats (F0) received a GBH through food, in a dose of 2 mg (GBH-LD: GBH-low dose group) or 200 mg (GBH-HD: GBH-high dose group) of glyphosate/kg bw/day from gestational day (GD) 9 until weaning. Body weight gain and vaginal canal-opening of F1 females were recorded. Sexually mature F1 females were mated to evaluate their reproductive performance by assessing the pregnancy rate, and on GD19, the number of corpora lutea, the implantation sites (IS) and resorption sites. To analyze second-generation effects on F2 offspring, we analyzed the fetal morphology on GD19, and assessed the fetal length and weight, and the placental weight. GBH exposure neither altered the body weight gain of F1 females, nor vaginal opening onset. Although all GBH-exposed F1 rats became pregnant, a lower number of IS was detected. F2 offspring from both GBH groups showed delayed growth, evidenced by lower fetal weight and length, associated with a higher incidence of small for gestational age fetuses. In addition, higher placental weight and placental index were found in F2 offspring from GBH-HD dams. Surprisingly, structural congenital anomalies (conjoined fetuses and abnormally developed limbs) were detected in the F2 offspring from GBH-HD group. In conclusion, perinatal exposure to low doses of a GBH impaired female reproductive performance and induced fetal growth retardation and structural congenital anomalies in F2 offspring.

Keywords

Glyphosate-based herbicide Uterus Reproductive performance Feto-placental parameters 

Notes

Acknowledgements

We thank Juan Grant and Juan C. Villarreal for technical assistance and animal care. We are grateful to Department of Mathematics and Laboratorio de Investigación y Servicios en Bioestadística (LISEB), in particular to Professor Stella Vaira, from Facultad de Bioquímica y Ciencias Biológicas (UNL) for the help with the statistical analyses. This work was supported by grants from the UNL (CAI+D 2016 PIC 50420150100085LI), the Argentine National Agency of Scientific and Technological Promotion (ANPCyT; PICT 2014 N° 2125, PICT 2014 N° 1522, PICT 2014 N° 1628) and CONICET. MMM, JV, and EHL are Career Investigators of the CONICET. VL is a fellow of Bunge and Born Foundation (Argentina); GP is an undergraduate student of Facultad de Bioquímica y Ciencias Biológicas (UNL); MRR is Professor of Facultad de Ingeniería Química (UNL); LDD is a fellow of the CONICET.

Compliance with ethical standards

Ethical standards

The manuscript does not contain clinical studies or patient data.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of the animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Acosta-Maldonado B, Sánchez-Ramírez B, Reza-López S, Levario-Carrillo M (2009) Effects of exposure to pesticides during pregnancy on placental maturity and weight of newborns: a cross-sectional pilot study in women from the Chihuahua State, Mexico. Hum Exp Toxicol 28:451–459CrossRefGoogle Scholar
  2. Adeeko A et al (2003) Effects of in utero tributyltin chloride exposure in the rat on pregnancy outcome. Toxicol Sci 74:407–415CrossRefGoogle Scholar
  3. Altamirano GA, Muñoz-de-Toro M, Luque EH, Gómez AL, Delconte MB, Kass L (2015) Milk lipid composition is modified by perinatal exposure to bisphenol A. Mol Cell Endocrinol 411:258–267CrossRefGoogle Scholar
  4. Anadón A et al (2009) Toxicokinetics of glyphosate and its metabolite aminomethyl phosphonic acid in rats. Toxicol Lett 190:91–95CrossRefGoogle Scholar
  5. Anway MD, Cupp A, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469CrossRefGoogle Scholar
  6. Anway MD, Leathers C, Skinner MK (2006) Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147:5515–5523CrossRefGoogle Scholar
  7. Arregui MC, Lenardon A, Sanchez D, Maitre MI, Scotta R, Enrique S (2004) Monitoring glyphosate residues in transgenic glyphosate-resistant soybean. Pest Manag Sci 60:163–166CrossRefGoogle Scholar
  8. Avila-Vazquez M, Maturano E, Etchegoyen A, Difilippo F, Maclean B (2017) Association between cancer and environmental exposure to glyphosate. Int J Clin Med 8:73–85CrossRefGoogle Scholar
  9. Bai SH, Ogbourne SM (2016) Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res 23:18988–19001CrossRefGoogle Scholar
  10. Barker DJ (1995) Fetal origins of coronary heart disease. BMJ 311:171–174CrossRefGoogle Scholar
  11. Barker DJ, Hales CN, Fall C, Osmond C, Phipps K, Clark P (1993) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36:62–67CrossRefGoogle Scholar
  12. Barron S, Thomson A (1983) Obstetrical epidemiology. Academic Press, LondonGoogle Scholar
  13. Battaglin W, Kolpin D, Scribner E, Kuivila K, Sandstrom M (2005) Glyphosate, other herbicides, and transformation products in Midwestern streams. J Am Water Resour Assoc 41:323–332CrossRefGoogle Scholar
  14. Battaglin W, Meyer M, Kuivila K, Dietze J (2014) Glyphosate and its degradation product AMPA occur frequently and widely in US soils, surface water, groundwater, and precipitation. J Am Water Resour Assoc 50:275–290CrossRefGoogle Scholar
  15. Benachour N, Séralini GE (2009) Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol 22:97–105CrossRefGoogle Scholar
  16. Benbrook CM (2016) Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur 28:3CrossRefGoogle Scholar
  17. Bernal J, Bernal JL, Martin MT, Nozal MJ, Anadón A, Martínez-Larrañaga MR, Martínez MA (2010) Development and validation of a liquid chromatography–fluorescence–mass spectrometry method to measure glyphosate and aminomethylphosphonic acid in rat plasma. J Chromatogr B 878:3290–3296CrossRefGoogle Scholar
  18. Beuret CJ, Zirulnik F, Giménez MS (2005) Effect of the herbicide glyphosate on liver lipoperoxidation in pregnant rats and their fetuses. Reprod Toxicol 19:501–504CrossRefGoogle Scholar
  19. Bromilow RH, Chamberlain K (2000) The herbicide glyphosate and related molecules: physicochemical and structural factors determining their mobility in phloem. Pest Manag Sci 56:368–373CrossRefGoogle Scholar
  20. Bruner-Tran KL, Osteen KG (2011) Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations. Reprod Toxicol 31:344–350CrossRefGoogle Scholar
  21. Burdorf A, Brand T, Jaddoe V, Hofman A, Mackenbach J, Steegers E (2011) The effects of work-related maternal risk factors on time to pregnancy, preterm birth and birth weight: the Generation R study. Occup Environ Med 68:197CrossRefGoogle Scholar
  22. Burkhardt T, Schäffer L, Schneider C, Zimmermann R, Kurmanavicius J (2006) Reference values for the weight of freshly delivered term placentas and for placental weight–birth weight ratios. Eur J Obstet Gynecol Reprod Biol 128:248–252CrossRefGoogle Scholar
  23. Chang FC, Simcik MF, Capel PD (2011) Occurrence and fate of the herbicide glyphosate and its degradate aminomethylphosphonic acid in the atmosphere. Environ Toxicol Chem 30:548–555CrossRefGoogle Scholar
  24. Chevrier C, Warembourg C, Gaudreau E, Monfort C, Le Blanc A, Guldner L, Cordier S (2013) Organochlorine pesticides, polychlorinated biphenyls, seafood consumption, and time-to-pregnancy. Epidemiology 24:251–260CrossRefGoogle Scholar
  25. Chiu Y et al (2015) Fruit and vegetable intake and their pesticide residues in relation to semen quality among men from a fertility clinic. Hum Reprod 30:1342–1351CrossRefGoogle Scholar
  26. Cuhra M, Bøhn T, Cuhra P (2016) Glyphosate: too much of a good thing? Front Environ Sci 4:28CrossRefGoogle Scholar
  27. Dallegrave E, Mantese FD, Oliveira RT, Andrade AJ, Dalsenter PR, Langeloh A (2007) Pre-and postnatal toxicity of the commercial glyphosate formulation in Wistar rats. Arch Toxicol 81:665–673CrossRefGoogle Scholar
  28. Defarge N, Takács E, Lozano VL, Mesnage R, Spiroux de Vendômois J, Séralini GE, Székács A (2016) Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels. Int J Environ Res Public Health 13:264.  https://doi.org/10.3390/ijerph13030264 CrossRefPubMedCentralGoogle Scholar
  29. Den Hond E et al (2015) Human exposure to endocrine disrupting chemicals and fertility: a case–control study in male subfertility patients. Environ Int 84:154–160CrossRefGoogle Scholar
  30. Drake AJ, Liu L, Kerrigan D, Meehan RR, Seckl JR (2011) Multigenerational programming in the glucocorticoid programmed rat is associated with generation-specific and parent of origin effects. Epigenetics 6:1334–1343CrossRefGoogle Scholar
  31. EPA (2017) Glyphosate. Dietary exposure analysis in support of registration review. https://www.regulations.gov/document?D=EPA-HQ-OPP-2009-0361-0071 Accessed 12 Apr 2018
  32. Fischer R, Byerlee D, Edmeades G (2014) Crop yields and global food security: will yield increase continue to feed the world? Australian Centre for International Agricultural Research, CanberraGoogle Scholar
  33. Fowden A, Forhead A, Coan P, Burton G (2008) The placenta and intrauterine programming. J Neuroendocrinol 20:439–450CrossRefGoogle Scholar
  34. Gallegos CE, Bartos M, Bras C, Gumilar F, Antonelli MC, Minetti A (2016) Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring. Neurotoxicology 53:20–28CrossRefGoogle Scholar
  35. García J, Ventura MI, Requena M, Hernández AF, Parrón T, Alarcón R (2017) Association of reproductive disorders and male congenital anomalies with environmental exposure to endocrine active pesticides. Reprod Toxicol 71:95–100CrossRefGoogle Scholar
  36. Guerrero Schimpf M, Milesi MM, Ingaramo PI, Luque EH, Varayoud J (2017) Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus. Toxicology 376:2–14CrossRefGoogle Scholar
  37. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter P (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303:1019–1022CrossRefGoogle Scholar
  38. Ibáñez L, Potau N, Francois I, de Zegher F (1998) Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab 83:3558–3562CrossRefGoogle Scholar
  39. Ingaramo PI, Varayoud J, Milesi MM, Guerrero Schimpf M, Muñoz-de-Toro M, Luque EH (2016) Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction. Reproduction 152:403–415CrossRefGoogle Scholar
  40. Ingaramo PI, Varayoud J, Milesi MM, Guerrero Schimpf M, Alarcón R, Muñoz-de-Toro M, Luque EH (2017) Neonatal exposure to a glyphosate-based herbicide alters uterine decidualization in rats. Reprod Toxicol 73:87–95CrossRefGoogle Scholar
  41. Kass L, Altamirano GA, Bosquiazzo VL, Luque EH, Muñoz-de-Toro M (2012) Perinatal exposure to xenoestrogens impairs mammary gland differentiation and modifies milk composition in Wistar rats. Reprod Toxicol 33:390–400CrossRefGoogle Scholar
  42. Kongtip P et al (2017) Glyphosate and paraquat in maternal and fetal serums in thai women. J Agromed 22:282–289CrossRefGoogle Scholar
  43. Kramer MS (1987) Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 65:663PubMedPubMedCentralGoogle Scholar
  44. Krüger M, Schledorn P, Schrödl W, Hoppe H-W, Lutz W, Shehata AA (2014a) Detection of glyphosate residues in animals and humans. J Environ Anal Toxicol 4:210.  https://doi.org/10.4172/2161-0525.1000210 CrossRefGoogle Scholar
  45. Krüger M, Schrödl W, Pedersen I, Shehata AA (2014b) Detection of glyphosate in malformed piglets. J Environ Anal Toxicol 4:230.  https://doi.org/10.4172/2161-0525.1000230 CrossRefGoogle Scholar
  46. Londero AP, Bertozzi S, Visentin S, Fruscalzo A, Driul L, Marchesoni D (2013) High placental index and poor pregnancy outcomes: a retrospective study of 18,386 pregnancies. Gynecol Endocrinol 29:666–669CrossRefGoogle Scholar
  47. MacDonald MG, Seshia MM, Mullett MD (2005) Avery’s neonatology pathophysiology and management of the newborn. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  48. Macdonald E, Natale R, Regnault T, Koval J, Campbell M (2014) Obstetric conditions and the placental weight ratio. Placenta 35:582–586CrossRefGoogle Scholar
  49. Macklon N (2017) Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertil Steril 108:9–14CrossRefGoogle Scholar
  50. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2012a) Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One 7(9):e46249CrossRefGoogle Scholar
  51. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2012b) Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations. Reprod Toxicol 34:708–719CrossRefGoogle Scholar
  52. Mañas F, Peralta L, Raviolo J, Ovando HG, Weyers A, Ugnia L, Cid MG, Larripa I, Gorla N (2009) Genotoxicity of AMPA, the environmental metabolite of glyphosate, assessed by the Comet assay and cytogenetic tests. Ecotoxicol Environ Safety 72(3):834–837CrossRefGoogle Scholar
  53. Mendez MJ, Aimar SB, Aparicio VC, Haberkon NBR, Buschiazzo DE, De Gerónimo E, Costa JL (2017) Glyphosate and aminomethylphosphonic acid (AMPA) contents in the respirable dust emitted by an agricultural soil of the central semiarid region of Argentina. Aeol Res 29:23–29CrossRefGoogle Scholar
  54. Mesnage R, Bernay B, Séralini GE (2013) Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology 313:122–128CrossRefGoogle Scholar
  55. Mesnage R et al (2017) Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol 108:30–42CrossRefGoogle Scholar
  56. Milesi MM, Alarcón R, Ramos JG, Muñoz-de-Toro M, Luque EH, Varayoud J (2015) Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats. Mol Cell Endocrinol 401:248–259CrossRefGoogle Scholar
  57. Montes G, Luque E (1988) Effects of ovarian steroids on vaginal smears in the rat. Acta Anat 133:192–199CrossRefGoogle Scholar
  58. Mostafalou S, Abdollahi M (2017) Pesticides: an update of human exposure and toxicity. Arch Toxicol 91:549–599CrossRefGoogle Scholar
  59. Myers JP et al (2016) Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health 15:19.  https://doi.org/10.1186/s12940-016-0117-0 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Niemann L, Sieke C, Pfeil R, Solecki R (2015) A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers. Journal für Verbraucherschutz Lebensmittelsicherheit 10:3–12CrossRefGoogle Scholar
  61. Nilsson EE, Anway MD, Stanfield J, Skinner MK (2008) Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease. Reproduction 135:713–721CrossRefGoogle Scholar
  62. Oulkar DP, Hingmire S, Goon A, Jadhav M, Ugare B, Thekkumpurath AS, Banerjee K (2017) Optimization and validation of a residue analysis method for glyphosate, glufosinate, and their metabolites in plant matrixes by liquid chromatography with tandem mass spectrometry. J Assoc Off Anal Chem Int 100:631–639Google Scholar
  63. Paganelli A, Gnazzo V, Acosta H, López SL, Carrasco AE (2010) Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling. Chem Res Toxicol 23:1586–1595CrossRefGoogle Scholar
  64. Parvez S et al (2018) Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study. Environ Health 17:23.  https://doi.org/10.1186/s12940-018-0367-0 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Perego MC, Caloni F, Cortinovis C, Schutz LF, Albonico M, Tsuzukibashi D, Spicer LJ (2017) Influence of a roundup formulation on glyphosate effects on steroidogenesis and proliferation of bovine granulosa cells in vitro. Chemosphere 188:274–279CrossRefGoogle Scholar
  66. Perobelli JE, Alves TR, de Toledo FC, Fernandez CDB, Anselmo-Franci JA, Klinefelter GR, Kempinas WDG (2012) Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty. Reprod Toxicol 33:308–315CrossRefGoogle Scholar
  67. Peruzzo PJ, Porta AA, Ronco AE (2008) Levels of glyphosate in surface waters, sediments and soils associated with direct sowing soybean cultivation in north pampasic region of Argentina. Environ Pollut 156:61–66CrossRefGoogle Scholar
  68. Primost JE, Marino DJ, Aparicio VC, Costa JL, Carriquiriborde P (2017) Glyphosate and AMPA,“pseudo-persistent” pollutants under real-world agricultural management practices in the Mesopotamic Pampas agroecosystem, Argentina. Environ Pollut 229:771–779CrossRefGoogle Scholar
  69. Quintana MM, Vera B, Magnarelli G, Guiñazú N, Rovedatti MG (2017) Neonatal, placental, and umbilical cord blood parameters in pregnant women residing in areas with intensive pesticide application. Environ Sci Pollut Res 24:20736–20746CrossRefGoogle Scholar
  70. Rappazzo KM, Warren JL, Meyer RE, Herring AH, Sanders AP, Brownstein NC, Luben TJ (2016) Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort. Birth Defects Res Part A Clin Mol Teratol 106:240–249CrossRefGoogle Scholar
  71. Razi S, Rezaeian M, Dehkordi FG, Manshoori A, Goujani R, Vazirinejad R (2016) Exposure to pistachio pesticides and stillbirth: a case–control study. Epidemiol Health 38:e2016016.  https://doi.org/10.4178/epih.e2016016 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE (2005) Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ Health Perspect 113:716–720CrossRefGoogle Scholar
  73. Romano MA et al (2012) Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression. Arch Toxicol 86:663–673CrossRefGoogle Scholar
  74. Ronco A, Marino D, Abelando M, Almada P, Apartin C (2016) Water quality of the main tributaries of the Paraná Basin: glyphosate and AMPA in surface water and bottom sediments. Environ Monit Assess 188:1–13CrossRefGoogle Scholar
  75. Roustan A, Aye M, De Meo M, Di Giorgio C (2014) Genotoxicity of mixtures of glyphosate and atrazine and their environmental transformation products before and after photoactivation. Chemosphere 108:93–100CrossRefGoogle Scholar
  76. Roy NM, Carneiro B, Ochs J (2016) Glyphosate induces neurotoxicity in zebrafish. Environ Toxicol Pharmacol 42:45–54CrossRefGoogle Scholar
  77. Saenger P, Czernichow P, Hughes I, Reiter EO (2007) Small for gestational age: short stature and beyond. Endocr Rev 28:219–251CrossRefGoogle Scholar
  78. SANTE (2015) Guidance document on analytical quality control and method validation procedures for pesticides residues analysis in food and feed. European commission, SANTE/11945/2015. http://www.eurl-pesticides.eu Accessed 22 Dec 2017
  79. Sasal MC et al (2015) Glyphosate loss by runoff and its relationship with phosphorus fertilization. J Agric Food Chem 63:4444–4448CrossRefGoogle Scholar
  80. Sathyanarayana S, Basso O, Karr CJ, Lozano P, Alavanja M, Sandler DP, Hoppin JA (2010) Maternal pesticide use and birth weight in the agricultural health study. J Agromed 15:127–136CrossRefGoogle Scholar
  81. Skinner MK, Manikkam M, Guerrero-Bosagna C (2011) Epigenetic transgenerational actions of endocrine disruptors. Reprod Toxicol 31:337–343CrossRefGoogle Scholar
  82. Skinner MK, Haque CG-BM., Nilsson E, Bhandari R, McCarrey JR (2013) Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line. PLoS One 8(7):e66318CrossRefGoogle Scholar
  83. Skogen JC, Øverland S (2012) The fetal origins of adult disease: a narrative review of the epidemiological literature. J R Soc Med Short Rep 3:1–7CrossRefGoogle Scholar
  84. Test Biotech (2013) High levels of residues from spraying with glyphosate found in soybeans in Argentina. http://www.testbiotech.org/en/node/926 Accessed 12 Apr 2018
  85. Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J (2013) Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol 59:129–136CrossRefGoogle Scholar
  86. Vandenberg LN et al (2017) Is it time to reassess current safety standards for glyphosate-based herbicides? J Epidemiol Community Health 71:613–618CrossRefGoogle Scholar
  87. Varayoud J, Ramos JG, Muñoz-de-Toro M, Luque EH (2014) Long-lasting effects of neonatal bisphenol A exposure on the implantation process. Vitam Horm 94:253–275CrossRefGoogle Scholar
  88. Varayoud J, Durando M, Ramos JG, Milesi MM, Ingaramo PI, Muñoz-de-Toro M, Luque EH (2017) Effects of a glyphosate-based herbicide on the uterus of adult ovariectomized rats. Environ Toxicol 32:1191–1201CrossRefGoogle Scholar
  89. Verkauskiene R, Petraitiene I, Albertsson WK (2013) Puberty in children born small for gestational age. Horm Res Paediatr 80:69–77CrossRefGoogle Scholar
  90. Wellstead JR, Bruce NW, Rahima A (1989) Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat. Anat Rec 225:101–105CrossRefGoogle Scholar
  91. WHO (2017) Sexual and reproductive health: infertility is a global public health issue. http://www.who.int/reproductivehealth/topics/infertility/perspective/en/ Accessed 22 Dec 2017
  92. Whyatt RM et al (2004) Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environ Health Perspect 112:1125–1132CrossRefGoogle Scholar
  93. Williams GM, Kroes R, Munro IC (2000) Safety evaluation and risk assessment of the herbicide roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 31:117–165CrossRefGoogle Scholar
  94. Ziv-Gal A, Flaws JA (2016) Evidence for bisphenol A-induced female infertility: a review (2007–2016). Fertil Steril 106:827–856CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • María M. Milesi
    • 1
  • Virginia Lorenz
    • 1
  • Guillermina Pacini
    • 1
  • María R. Repetti
    • 2
  • Luisina D. Demonte
    • 2
  • Jorgelina Varayoud
    • 1
  • Enrique H. Luque
    • 1
  1. 1.Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias BiológicasUniversidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Santa FeArgentina
  2. 2.Programa de Investigación y Análisis de Residuos y Contaminantes Químicos (PRINARC), Facultad de Ingeniería QuímicaUNLSanta FeArgentina

Personalised recommendations