Mycotoxin ingestion during late gestation alters placentome structure, cotyledon transcriptome, and fetal development in pregnant sheep

Authors: BRITT, JESSI - CLEMSON UNIVERSITY; GREENE, MASLYN - CLEMSON UNIVERSITY; Klotz, James; JUSTICE, S. - CLEMSON UNIVERSITY; POWELL, R. - CLEMSON UNIVERSITY; NOORAI, R. - CLEMSON UNIVERSITY; BRUCE, T. - CLEMSON UNIVERSITY; DUCKETT, SUSAN - CLEMSON UNIVERSITY

Submitted to: Human and Experimental Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/18/2022
Publication Date: 8/10/2022
Citation: Britt, J.L., Greene, M.A., Klotz, J.L., Justice, S.M., Powell, R.R., Noorai, R.E., Bruce, T.F., Duckett, S.K. 2022. Mycotoxin ingestion during late gestation alters placentome structure, cotyledon transcriptome, and fetal development in pregnant sheep. Human and Experimental Toxicology. 41. https://doi.org/10.1177/09603271221119177.
DOI: https://doi.org/10.1177/09603271221119177

Interpretive Summary: rgot alkaloids found in tall fescue, a predominant cool season pasture grass in the eastern United States have been documented to cause intrauterine growth restriction in sheep. This results in increased losses in overall production by sheep producers and likely other producers of grazing livestock. This study used the pregnant ewe model and looked at the effects of ergot alkaloids on morphology and gene expression of reproductive tissues at 2 different time points in gestation. The results of this study demonstrated that ergot alkaloids alter the remodeling of reproductive tissues that support increased fetal growth later in gestation. These alterations result in insufficiencies that yield an abnormally developed fetus frequently observed in ewes grazing ergot alkaloid-containing pastures. This work does a very thorough characterization of the impacts that ergot alkaloids have on the fetal and maternal perspectives during gestation. This work was basic in in nature and will likely be primarily of interest to other researchers.

Technical Abstract: Pregnant Suffolk ewes (n = 19; 81.2kg ± 7.7) estimated to be carrying twins were assigned to endophyte-infected tall fescue seed (E+; 4.14 µg ergovaline + ergovalinine/g seed) or a control diet (CON; 0 µg ergovaline + ergovalinine) and evaluated at different stages of gestation (gd85 [pre-treatment, n = 3], gd110 [n = 4/treatment] or gd133 [n = 4/treatment). Ewes were individually fed a basal diet with (E+) or without (CON) endophyte-infected tall fescue seed from gd86 to gd110 or gd133. A terminal necropsy was performed, and uterine components were evaluated for size, weight, and type. Data were analyzed using a priori contrasts to test effects of stage of gestation (gd85 vs. gd110 or gd110 vs. gd133) and adaptive responses to feeding E+ fescue seed versus CON at gd110 and gd133. Serum prolactin concentrations were greater (P < 0.05) at gd110 than gd85, and then remained constant to gd133. Feeding E+ tall fescue seed reduced (P < 0.05) serum prolactin concentrations compared to CON at both gd110 and gd133. From gd85 to gd110, placentome type and number changed from type A to type B (P < 0.05) but did not change (P > 0.05) after gd110. Total fetal weight per ewe increased 2977 g from gd85 to gd110 (P = 0.011) and then 3151 g from gd110 to 133 (P = 0.012). Brain weight as a percentage of fetal body weight was higher (P = 0.029) for E+ fetuses on gd110 compared to CON, which demonstrates asymmetrical growth and intrauterine growth restriction (IUGR). In total, 15,961 genes were identified in the cotyledon through mapping to the ovine genome across all samples. There were 136 genes differentially expressed (FDR < 0.05; log2foldchange < -1 and > 1) from gd85 to gd110 with ovarian steroidogenesis and steroid biosynthesis pathways enriched and 469 genes differentially expressed from gd110 to gd133 with ribosome and oxidative phosphorylation pathways enriched. Exposure to E+ fescue resulted in differential expression of 22 genes at gd110 but only one gene at gd133 compared to CON. These results show that there are major changes in fetal growth and placental remodeling during the late gestation period that are influenced by exposure to ergot alkaloids from endophyte-infected tall fescue seed; however, major changes in the transcriptome of the cotyledon tissue in response to E+ fescue were not observed and other factors must be involved in the reduction of placental efficiency and fetal growth observed with E+ fescue exposure.