Table 4.
Effects of glyphosate (active ingredient) (Gly) and glyphosate-based herbicides (GBHs) associated with female fertility and those reported in the successive generations (F1, F2 or F3) of mammalian offspring after maternal exposure.
| Compound tested | Exposure type | Fertility associated effects | F1, F2 or F3 offspring effects | Reference |
|---|---|---|---|---|
| -GBH: Magnum Super II -Gly |
Model: pregnant female rat Exposure: trough food from gestational day (GD)9 to lactational day (LD)21 Dose: 2 mg Gly/kg bw/day Target of study: uterus |
F1 female rats
GD5: Gly and GBH: -increased E2 serum levels -altered expression of implantation related- molecules: (ERα, Hoxa10 and Lif) GD19: Gly and GBH: -increased rate of preimplantation losses |
Gly:
-decreased weight of F1 male pups at birth |
(31) |
| -GBH: Roundup Full II |
Model: pregnant female rat Exposure: subcutaneous injections from postnatal day (PND)1 to PND7 Dose: 2 mg Gly/kg bw/day Target of study: uterus |
GD9:
-altered endometrial decidualization process -increased proliferation (Ki67) GD19: -increased rate of postimplantation losses |
NR | (34) |
| -GBH: Roundup -Gly |
Model: pregnant female mouse Exposure: trough water from GD1 to GD19 Concentration: 5 mg Gly/ml Target of study: ovary, hypothalamus and pituitary gland. |
GD19:
Gly and GBH: -decreased ovary weight and altered ovarian histology. -decreased progesterone serum levels -altered expression of genes involved in hormonal balance in hypothalamus, pituitary gland and ovary: GnRH, LHR and3β-HSD -altered serum and ovarian markers of oxidative response Gly: -increased estradiol serum levels Gly or GBH -specific treatment-related differences |
Gly:
-altered sex ratio of F1 fetuses (increased male to female ratio) |
(36) |
| -GBH: Magnum Super II |
Model: pregnant female rat Exposure: through food from GD9 to LD21. Dose: 350 mg Gly/kg bw/day Target of study: uterus |
F1 female rats
GD5: -increased ERα mRNA expression by increasing ERα-O transcript variant -Epigenetic alterations in the O promoter of ERα |
NR | (37) |
| -Gly |
Model: pregnant female rat (F0) Exposure: trough daily intraperitoneal (ip) injections from GD8 to GD14 Dose: 25 mg Gly/kg bw/day Target of study: multiple organs |
-no changes in fertility rates | -decreased body weight at weaning in F1 offspring -increased age at puberty for F1 and F2 generations -increased obesity in F2 and F3 generations -increased frequency of histological alterations in F1, F2 and F3 generations (ovary, kidney, testis, prostate) -parturition abnormalities in F2 and F3 dams -increased tumor development in F2 generation (mammary adenomas) -differential methylation genes in sperm from F1, F2 and F3 generations |
(38) |
| -GBH: Magnum Super II |
Model: pregnant female rat (F0) Exposure: through food from GD9 to LD21. Dose: 2 and 200 mg Gly/kg bw/day Target of study: uterus, placenta, fetal parameters |
F1 female rats
GD19: 200 mg Gly/kg bw/day -increased rate of preimplantation losses |
F2 offspring
GD19: 200 mg Gly/kg bw/day: -decreased fetal weight and length -increased placental index -structural congenital anomalies 2 mg Gly/kg bw/day: -decreased fetal weight |
(121, 122) |
| -GBH: Roundup |
Model: pregnant female rat Exposure: by gavage from GD6 to GD15 Dose: 500, 750 and 1000 mg Gly/kg bw/day Target of study: multiple organs |
-no changes associated with female fertility |
All doses:
-increased occurrence of delayed ossification in several body structures in F1 fetuses |
(123) |
| -GBH: Roundup Full II -Mixture (MIX): commercial formulations of Gly + endosulfan (Endo) |
Model: neonatal and pregnant female rat Exposure: subcutaneous injections from PND1 to PND7 Dose: 2 mg Gly/kg bw/day or 2 mg Gly/kg bw/day + 600 µg Endo/kg bw/day Target of study: uterus |
PND8
:
GBH and MIX: -increased incidence of luminal epithelial hyperplasia -increased PR and Hoxa10 protein expression GD19: GBH and MIX: -increased rate of postimplantation losses. |
NR | (127) |
| -GBH: Roundup -Mixture (MIX): commercial formulations of Gly + Paraquat (Pq) |
Model: pregnant female rat Exposure: subcutaneous injections from GD1 to GD7 Dose: 500 mg Gly/kg bw/day or 500 mg Gly/kg bw/day + 50 mg Pq/kg bw/day Target of study: uterus, ovary and embryonic cells |
GD7:
GBH and MIX: -decreased body and ovary weight -decreased number of corpora lutea -increased rate of preimplantation losses -decreased surface and glandular epithelia and diameter of endometrial glands MIX: -disorganization of the cytotrophoblast and cell degeneration within the blastocyte cavity |
NR | (128) |
| -GBH: Kalach 360 SL |
Model: adult female rat Exposure: trough water during 60 days Dose: 126 and 315 mg Gly/kg bw/day Target of study: ovary |
At the end of the treatment:
-impaired folliculogenesis and ovary development. -necrosis, vacuolisation of follicles, dissociated oocytes and granulosa cells. -increased atretic follicles. -decreased E2 serum levels -decreased antioxidant enzyme activities: catalase (CAT), superoxide dismutase and glutathione peroxidase (GP). |
NR | (129) |
| -GBH: Roundup Bioflow -Gly |
Model: pregnant female rat Exposure: through drinking water from GD6 to 6-weeks or 13 weeks after weaning Dose: 1.75 mg Gly/kg bw/day Target of study: multiple targets |
NR |
F1 offspring
Gly and GBH: -altered developmental parameters (anogenital distance, age at first estrous) -altered sexual hormone concentrations -specific sex-related and treatment-related differences |
(173) |
| -GBH: Roundup-Gly |
Model: pregnant female mouse Exposure: trough drinking water from GD1 to GD21 Dose: 5 mg Gly/ml Target of study: liver |
NR |
F1 offspring
Gly and GBH: -decreased body weight at weaning -disruption of lipid metabolism |
(174) |
| -GBH: Glifloglex |
Model: pregnant female rat Exposure: trough drinking water from GD1 to LD21 Dose: 100 and 200 mg Gly/kg bw/day Target of study: brain |
NR |
F1 offspring
-early onset of cliff aversion reflex and auditory canal opening. -decreased locomotor activity and anxiety levels -exacerbated emotionality |
(175) |
| -GBH: Glifloglex |
Model: pregnant female rat Exposure: trough drinking water from GD1 to LD21 Dose: 100 and 200 mg Gly/kg bw/day Target of study: brain |
NR |
F1 offspring
-altered antioxidant status -altered enzymes activity involved in glutamatergic and cholinergic systems -impairment in recognition memory |
(176) |
| -GBH: Roundup |
Model: pregnant female rat Exposure: trough oral gavage from GD0 to LD21 Dose: 250 and 500 mg Gly/kg bw/day Target of study: brain |
-decreased fertility rate and gestational index |
F1 offspring
-decreased number of pups per litter -decreased body weight on PND15 and PND21 Offspring: delayed reflexes and altered motor development Adults: decreased locomotor activity, sociability, learning and impaired memory |
(177) |
| -Gly |
Model: pregnant female rat Exposure: ip injections every 48 hs from GD8 to GD20 Dose: 24 and 35 mg Gly/kg bw/day Target of study: brain |
NR |
F1 offspring
-decreased body weight in pups from PND19 -altered dose-dependent reflexes development, motor activity and cognitive function -altered Wnt5a-CaMKII pathway in fetal hippocampus |
(178) |
| -GBH: Roundup Transorb |
Model: pregnant female rat Exposure: by oral gavage from GD18 to LD5 Dose: 5 and 50 mg Gly/kg bw/day Target of study: brain (cerebellum and cortex) |
NR |
F1 male offspring (PND90)
-altered gene expression involved in oxidant defense, inflammation and lipid metabolism -correlation of changes in gene expression with serum concentrations of oxidative stress-related metabolites |
(179) |
| -GBH: Roundup Maxload |
Model: pregnant female mouse Exposure: trough drinking water from GD5 to LD21 Dose: 12.5 mg Gly/kg bw/day Target of study: brain (prefrontal cortex, hippocampus and striatum) |
NR |
F1 juvenile offspring (PND28-PND35)
-autism spectrum disorder (ASD)-like behavioral abnormalities (cognitive and social interaction deficits) -increased soluble epoxide hydrolase (sEH) expression -ASD-like behaviors prevented by oral administration of an sEH inhibitor -abnormal composition of gut microbiota |
(180) |
3β-HSD, 3β-hydroxysteroid dehydrogenase; ASD, autism spectrum disorder; CaMKII, Ca2+/calmodulin-dependent protein kinase; CAT, catalase; Endo, endosulfan; ERα, estrogen receptor alpha; GBH, glyphosate based-herbicide; GD, gestational day; Gly, glyphosate (active ingredient); GP, glutathione peroxidase; Hoxa10, Homeobox A10; ip, intraperitoneal; LD, lactational day; Lif, Leukemia inhibitory factor; LHR, luteinizing hormone receptor; MIX, mixture; NR, Not reported; PND, postnatal day; PR, progesterone receptor; Pq, paraquat; sEH, soluble epoxide hydrolase; Wnt5a, wingless-type MMTV integration site.