PMID- 34953950
OWN - NLM
STAT- MEDLINE
DCOM- 20220118
LR  - 20231213
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 296
DP  - 2022 Mar 1
TI  - Altered uterine angiogenesis in rats treated with a glyphosate-based herbicide.
PG  - 118729
LID - S0269-7491(21)02311-3 [pii]
LID - 10.1016/j.envpol.2021.118729 [doi]
AB  - Glyphosate-based herbicides (GBHs) are the agrochemicals most used around the 
      globe. However, they might have adverse effects on human and animal health. 
      Previously, we showed that female rats neonatally exposed to GBHs exhibit altered 
      expression of morphogenetic molecules and biomarkers of uterine development. We 
      also observed a reduction in the size of implantation sites, altered expression 
      of decidualization-related molecules, and increased post-implantation losses. 
      Since decidualization comprises morphogenetic, biochemical and vascular changes, 
      here we investigated the effects of neonatal GBH exposure on uterine angiogenesis 
      in neonatal and pregnant rats. To achieve this, Wistar female rats were exposed 
      to saline solution or GBH (2 mg glyphosate/kg-bw/day) on post-natal days (PND) 1, 
      3, 5 and 7. On PND8, uterine samples were collected for developmental studies. On 
      PND90, the remaining females were mated and in the morning of gestational day 
      (GD) 9, the implantation sites were collected. Angiogenesis-related molecules and 
      cells involved in this process were identified and/or measured by 
      immunohistochemistry or RT-PCR. On PND8, GBH-treated rats showed increased 
      vascular endothelial growth factor (VEGF) expression and decreased Notch1, 
      inducible nitric oxide synthase (iNOS) and Angiopoietin-2 (Ang2) mRNA levels. 
      Vascular area, vessel diameter, endothelial cell proliferation, VEGF and Nestin 
      protein expression, and VEGF, Notch1, iNOS and cyclooxygenase-2 (Cox-2) genes 
      were downregulated in implantation sites of exposed females, while Ang2, VEGF 
      receptor 1 and interleukin-10 (IL-10) were increased. Mast cells and macrophages 
      were increased on PND8 and GD9 of treated rats. The increased Transforming growth 
      factor-beta expression in the antimesometrial zone and IL-10 mRNA expression 
      suggest that the M2 type is the predominant population of macrophages on 
      implantation sites. In conclusion, neonatal GBH exposure alters the expression of 
      angiogenesis-related molecules at neonatal uterine development and decidual 
      reaction, suggesting altered vascular support. These alterations might contribute 
      to the increased post-implantation losses observed in GBH-treated rats.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Ingaramo, Paola I
AU  - Ingaramo PI
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Santa Fe, Argentina. Electronic address: 
      paolaingar@gmail.com.
FAU - Alarcon, Ramiro
AU  - Alarcon R
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Santa Fe, Argentina.
FAU - Caglieris, Maria L
AU  - Caglieris ML
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, 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 - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Santa Fe, Argentina.
FAU - Munoz-de-Toro, Monica
AU  - Munoz-de-Toro M
AD  - Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquimica y 
      Ciencias Biologicas, Universidad Nacional del Litoral - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, 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 - Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Santa Fe, Argentina.
LA  - eng
PT  - Journal Article
DEP - 20211222
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (Herbicides)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Female
MH  - Glycine/analogs & derivatives/toxicity
MH  - *Herbicides/toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - Vascular Endothelial Growth Factor A
MH  - Glyphosate
OTO - NOTNLM
OT  - Agrochemical
OT  - Angiogenesis
OT  - Decidualization
OT  - Female fertility
OT  - Implantation sites
OT  - Uterus development
EDAT- 2021/12/27 06:00
MHDA- 2022/01/19 06:00
CRDT- 2021/12/26 20:34
PHST- 2021/09/26 00:00 [received]
PHST- 2021/12/02 00:00 [revised]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2021/12/27 06:00 [pubmed]
PHST- 2022/01/19 06:00 [medline]
PHST- 2021/12/26 20:34 [entrez]
AID - S0269-7491(21)02311-3 [pii]
AID - 10.1016/j.envpol.2021.118729 [doi]
PST - ppublish
SO  - Environ Pollut. 2022 Mar 1;296:118729. doi: 10.1016/j.envpol.2021.118729. Epub 
      2021 Dec 22.