The exposure to endocrine-disrupting compounds (EDCs), such as glyphosate-based herbicides (GBHs), during early life might alter female fertility. The aim of the present study was to evaluate the effects of neonatal exposure to a GBH on sheep uterine development. To achieve this, Friesian ewe lambs were exposed to GBH (2 mg/kg of body weight/day; n = 12) or vehicle (controls; n = 10) through s.c. injections, from postnatal day (PND) 1 to PND14; on PND45, the uteri were obtained to evaluate histomorphological and molecular parameters. Morphological parameters were determined by picrosirius-hematoxylin staining. Protein expression of Ki67 (as a cell proliferation marker), p27, and molecules involved in uterine organogenetic differentiation was measured by immunohistochemistry. We also determined the mRNA expression of the IGF molecular pathway by RT-PCR. Although histomorphology was not modified, the uteri of GBH-exposed ewe lambs showed lower cell proliferation, together with higher p27 protein expression. In addition, the uteri of GBH-exposed ewe lambs showed increased gene expression of insulin-like growth factor binding protein 3 (IGFBP-3), decreased expression of ERα in the luminal (LE) and glandular (GE) epithelia and in the subepithelial stroma (SS), and lower PR expression in the LE but higher in the GE and SS. In addition, GBH treatment decreased the uterine expression of Wnt5a in the GE, of Wnt7a in the SS, of β-catenin in the LE and GE, of Hoxa10 in the SS, and of Foxa2 in the GE as compared with controls. In conclusion, neonatal exposure to GBH decreased cell proliferation and altered the expression of molecules that control proliferation and development in the uterus. All these changes might have adverse consequences on uterine differentiation and functionality, affecting the female reproductive health of sheep. GBH may be responsible for uterine subfertility, acting as an EDC.

Muscle tissue was collected from ewes and lambs derived from farms throughout Scotland and sample concentrations of five endocrine disrupting compound groups were determined. Farms of origin were categorised according to geographic region. There were few statistically-significant differences with region or distance from cities. However, the magnitude of the difference between the highest and lowest mean values in ewe muscle from different regions exceeded 30% for 13 of the 15 compounds that were consistently detected in muscle, with animals derived from the industrialised region having the highest mean values for 11 of the 13 compounds. A less marked trend was apparent in the lamb muscle (8 of 13 highest were in the industrialised region). The physiological effects of such small differences in exposure to mixtures of pollutants remain to be determined.

Benzimidazoles are anthelmintics frequently used in sheep farming due to the high susceptibility of these animals to parasitic diseases. Sheep excreta are often disposed onto soils as a fertilizer, and they may contain benzimidazole residues that can contaminate soil and water. This work aimed to assess the leaching behavior of benzimidazole drugs (albendazole, fenbendazole, and thiabendazole) and their metabolites in two Brazilian soils of different textural classifications (sandy and clay), as well as sheep excreta-amended soils, following the OECD 312 Guidelines. Ewes received a single oral dose of 10 mg kg⁻¹ b.w. of either albendazole or fenbendazole. The feces were collected at 24, 48, 72, 96, and 120 h post-dose, and the parent drugs and their metabolites extracted using the QuEChERS approach and quantified by UHPLC-MS/MS. For the leaching assays, a benzimidazole solution was directly applied onto the soil columns, or an amount of 5 g of the medicated sheep feces was distributed over the top of the soil columns. In soil samples, benzimidazoles were extracted by solid-liquid extraction and quantified by UHPLC-MS/MS. For the leaching studies, atrazine was used as a reference substance to determine the relative mobility factor of the analytes of interest. Benzimidazoles were considered slightly to moderately mobile in both soils tested, with a leaching distance of up to 25 cm in a 30-cm soil column. Approximately 3 to 6% of the benzimidazoles present in ewe feces were able to leach into the soil columns. This finding is of concern since benzimidazoles are persistent in soil and may pose a risk to soil biota and induce the development of resistant strains of parasites.

Chlordecone (CLD) is an organochlorine pesticide used in banana fields of the French West Indies between 1972 and 1993. This use resulted in a long-term pollution of soils and the possible contamination of farm animals. Indeed, after involuntary ingestion of soil, CLD is absorbed and consequently leads to contaminated animals. The aim of this study was the determination of CLD half-life and the establishment of the linearity of CLD disappearance kinetics in non-lactating adult’s ewes. Chlordecone diluted in cremophor was intravenously administrated to ewes at different doses: 0.04, 0.2, or 1 mg kg⁻¹ body weight (n = 5 for each dose). Blood samples were collected from time t = 0 to time t = 84 days. Serum samples were extracted with a solid-phase extraction and analyzed by electron capture detection gas chromatography. A two-compartmental model was applied to the serum CLD kinetics. An additional statistical analysis was applied to the observed elimination parameters in serum according to the administrated dose, and no significant differences were detected. The linear elimination of CLD between 0.04 and 1 mg kg⁻¹ body weight allowed the possibility of ewe’s extrapolation half-life in this dose range. The estimated mean CLD half-life in ewes was 24 days. Overall, the results of this study will be useful to establish decontamination strategies in small ruminants reared in contaminated CLD areas. Graphical abstract Experimental design of the CLD toxicokinetic study in ewes

The aim of this study was to determine the effect of the supplementation of slow release bolus of selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), phosphorous (P), manganese (Mn), and iodine (I) at late gestation (60 day prepartum) on performance of Najdi ewes and their newborn. Twenty Najdi ewes at late gestation were randomly selected from a herd raised under an intensive system and equally divided into two groups (control and treated). Blood samples were collected from ewes and newborns at parturition. Body weights of newborns were taken at birth, 30 and 60 days. A significant (P < 0.05) increase in Cu and Co in blood of dams treated with boluses with an increase (P < 0.05) in blood P, Zn, Cu, Co, and Se of their newborn lambs were observed. Creatinine and triglyceride were significantly (P < 0.05) low in treated newborn while urea was significantly (P < 0.05) high in the same group. In dams, significantly (P < 0.05) low concentration of triglyceride was observed. Body weight of lambs from treated group at 30 days was significantly (P < 0.05) higher when compared with the control. In conclusion, bolus of trace minerals at late gestation improved some mineral status of ewes and the newborns with higher body weight.