Effects of subclinical pregnancy toxemia and L-carnitine supplementation on angiogenesis, energy metabolism, and fetal development in ewes

Abstract

Subclinical pregnancy toxemia (SPT) is a common metabolic disorder affecting small ruminants during late gestation under conditions of negative energy balance. This study investigated the effects of experimentally induced SPT on angiogenesis-related gene expression in uterine and placental tissues, hepatic energy metabolism-related gene expression, fetal and placental development, and selected serum biochemical parameters in ewes. The potential protective effects of L-carnitine supplementation were also evaluated. Nineteen crossbred Hamdani ewes were assigned to three groups: SPT (G1, n = 6), SPT supplemented with L-carnitine (G2, n = 7), and control (G3, n = 6). SPT was induced by dietary restriction from gestational day 100. Blood samples were collected on days 100, 110, 120, 130, and 138, and tissues were collected at day 138 for morphometric, histopathological, and molecular analyses. Maternal body weight, uterine weight, fetal weight, and placentome dimensions were significantly lower in G1 than in controls (p < 0.05). Histopathology revealed significant hepatic lipid accumulation in G1. Serum β-hydroxybutyrate, triglyceride, and cholesterol concentrations increased, whereas glucose concentrations decreased in G1 during late gestation (p < 0.05). L-carnitine supplementation improved these metabolic alterations in G2. Placental expression of VEGF, VEGFR1, and VEGFR2 was significantly downregulated in G1 compared with G2 and G3 (p < 0.05). Hepatic DGAT1 expression increased significantly in G1 (p < 0.05), whereas GPD1 and GK expression remained unchanged. These findings indicate that SPT impairs fetal and placental development, disrupts angiogenic signaling, and alters hepatic lipid metabolism. Dietary L-carnitine supplementation may compensate these adverse effects and improve maternal metabolic status and placental function in ewes. © 2026 Elsevier B.V.