Toxicon 190 (2021) 3–10 Available online 27 November 2020 0041-0101/© 2020 Elsevier Ltd. All rights reserved. The effect of Ipomoea carnea on maternal reproductive outcomes and fetal and postnatal development in rats Andr´e Tadeu Gotardo a , Luciana Lucinio Lippi a , Kalan Bastos Violin b , Estela Maris Andrade Forell Bevilacqua c , Silvana Lima G´ orniak a, * a Research Centre for Veterinary Toxicology (CEPTOX), Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of S˜ ao Paulo, Pirassununga, SP, 05508-270, Brazil b Energy and Nuclear Research Institute, Material Science and Technology Center, University of S˜ ao Paulo, S˜ ao Paulo, SP, 05508-0002242, Brazil c Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S˜ ao Paulo, S˜ ao Paulo, Brazil A R T I C L E INFO Keywords: Ipomoea carnea Swainsonine Reproductive toxicology Placental toxicity Birth defects ABSTRACT Ipomoea carnea is a toxic plant found in Brazil and other tropical countries. The plant contains the alkaloids calystegines and swainsonine, which inhibit key cellular enzymes and cause systematic cell death. It is known that swainsonine is excreted in the amniotic fluid of dams exposed to the plant. Thus, the aim of this study was to verify whether the toxic effect of I. carnea on fetuses is due to exclusively the passage of the active principle of the plant through the placenta, or if the placentotoxic effect of swainsonine could collaborate in the adverse effects observed in the fetus. The teratogenic effects of exposure to the toxic principles of I. carnea were evaluated not only using the conventional protocol but also at later stages in the postnatal developmental period. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 3.0 or 7.0 g/kg body weight of I. carnea dry leaves. The plant did not induce changes in reproductive performance or biochemical profile of the dams. Dams that received the highest dose of I. carnea showed cytoplasmic vacuolization in the liver, kidney and placental tissue. I. carnea promoted different lectin binding patterns in different areas of placental tissue. No fetal skeletal or visceral malformations was observed. The postnatal evaluation revealed a lower litter weight and a lower pup body weight one day after birth in the group that received the highest dose of I. carnea. Physical milestones were unaffected by the treatments. Female pups from all experimental groups exhibited a delay in achieving a negative geotaxis response. The results show that the toxic principle of I. carnea produces injury in utero in mothers and fetuses, but these deleterious effects were better demonstrated using postnatal evaluation. 1. Introduction Ipomoea carnea Jacq. spp. fistulosa Choisy (Convolvulaceae) is a poisonous plant widely distributed in Brazil (Tokarnia et al., 2000) and other tropical countries (Austin and Hu´ aman, 1996). Natural toxicosis occurs when different farm animal species chronically ingest the plant; after prolonged periods of plant intake, the animals exhibit a variety of clinical signs, such as depression, general weakness, body weight loss, staggering gait, muscle tremors, ataxia, posterior paresis, and paralysis (Damir et al., 1987; De Balogh et al., 1999; Tokarnia et al., 2000; Schumaher-Henrique et al., 2003). Intoxication induces enzymatic dysfunction, which causes the accumulation of complex oligosaccharides in lysosomes. As a consequence, vacuolation becomes evident in different cells, mainly in the CNS (De Balogh et al., 1999; Schumaher-Henrique et al., 2003; Gotardo et al., 2012). Two kinds of toxic components were isolated from the plant, the nortropane alkaloids calystegines B1, B2, B3 and C1 and the most important active principle, the indolizidine alkaloid swainsonine (Molyneux et al., 1995; De Balogh et al., 1999; Haraguchi et al., 2003). Swainsonine is a potent inhibitor of two distinct intracellular enzymes, the lysosomal α-mannosidase, which results in lysosomal accumulation of incompletely processed oligosaccharides rich in a-mannosyl and b-N-acetyl glucosamine moieties inside vacuoles, which progresses to cellular function loss and, ultimately, to cell death (Tulsiani and Touser, 1983), and the Golgi mannosidase II enzyme, which causes alteration of * Corresponding author. School of Veterinary Medicine and Animal Sciences, University of S˜ao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, 05508-900, S˜ ao Paulo, SP, Brazil. E-mail address: gorniak@usp.br (S.L. G´ orniak). Contents lists available at ScienceDirect Toxicon journal homepage: http://www.elsevier.com/locate/toxicon https://doi.org/10.1016/j.toxicon.2020.11.012 Received 2 October 2020; Received in revised form 19 November 2020; Accepted 22 November 2020