PMID- 29947892 OWN - NLM STAT- MEDLINE DCOM- 20191028 LR - 20231213 IS - 1432-0738 (Electronic) IS - 0340-5761 (Linking) VI - 92 IP - 8 DP - 2018 Aug TI - Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats. PG - 2629-2643 LID - 10.1007/s00204-018-2236-6 [doi] AB - 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. FAU - Milesi, Maria M AU - Milesi MM AD - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Casilla de Correo 242, 3000, Santa Fe, Argentina. mmilesi@fbcb.unl.edu.ar. FAU - Lorenz, Virginia AU - Lorenz V AD - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Casilla de Correo 242, 3000, Santa Fe, Argentina. FAU - Pacini, Guillermina AU - Pacini G AD - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Casilla de Correo 242, 3000, Santa Fe, Argentina. FAU - Repetti, Maria R AU - Repetti MR AD - Programa de Investigacion y Analisis de Residuos y Contaminantes Quimicos (PRINARC), Facultad de Ingenieria Quimica, UNL, Santa Fe, Argentina. FAU - Demonte, Luisina D AU - Demonte LD AD - Programa de Investigacion y Analisis de Residuos y Contaminantes Quimicos (PRINARC), Facultad de Ingenieria Quimica, UNL, Santa Fe, Argentina. FAU - Varayoud, Jorgelina AU - Varayoud J AD - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Casilla de Correo 242, 3000, Santa Fe, Argentina. FAU - Luque, Enrique H AU - Luque EH AD - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Casilla de Correo 242, 3000, Santa Fe, Argentina. LA - eng PT - Journal Article DEP - 20180609 PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 0 (Herbicides) RN - 0 (Isoxazoles) RN - 0 (Tetrazoles) RN - J090588E6X (2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid) RN - TE7660XO1C (Glycine) SB - IM CIN - Arch Toxicol. 2019 Jan;93(1):207. PMID: 30456485 CIN - Arch Toxicol. 2019 Mar;93(3):831-832. PMID: 30725131 CIN - Arch Toxicol. 2019 Dec;93(12):3635-3638. PMID: 31720698 CIN - Arch Toxicol. 2020 Jan;94(1):351-352. PMID: 31853558 MH - Animals MH - Body Weight/drug effects MH - Female MH - Fetal Growth Retardation/chemically induced MH - Glycine/administration & dosage/*analogs & derivatives/toxicity MH - Herbicides/toxicity MH - Isoxazoles/blood MH - Lactation MH - Male MH - Placenta/drug effects/pathology MH - Pregnancy MH - Pregnancy Rate MH - Prenatal Exposure Delayed Effects/*chemically induced MH - Puberty/drug effects/physiology MH - Rats, Wistar MH - Reproduction/*drug effects/physiology MH - Tetrazoles/blood MH - Glyphosate OTO - NOTNLM OT - Feto-placental parameters OT - Glyphosate-based herbicide OT - Reproductive performance OT - Uterus EDAT- 2018/06/28 06:00 MHDA- 2019/10/29 06:00 CRDT- 2018/06/28 06:00 PHST- 2018/02/15 00:00 [received] PHST- 2018/06/04 00:00 [accepted] PHST- 2018/06/28 06:00 [pubmed] PHST- 2019/10/29 06:00 [medline] PHST- 2018/06/28 06:00 [entrez] AID - 10.1007/s00204-018-2236-6 [pii] AID - 10.1007/s00204-018-2236-6 [doi] PST - ppublish SO - Arch Toxicol. 2018 Aug;92(8):2629-2643. doi: 10.1007/s00204-018-2236-6. Epub 2018 Jun 9.