ENDOSULFAN ALTERS THE SIGNALING PATHWAYS THAT REGULATE OVIDUCTAL ADENOGENESIS IN THE BROAD-SNOUTED CAIMAN (Caiman latirostris) AND MODIFIES THE TEMPORAL PATTERN OF HISTOMORPHOLOGICAL CHANGES

TAVALIERI, Y.E.; SCHUERI, F.D.; LUQUE, E.H.; GALOPPO, G.H.; MUÑOZ DE TORO, M.

Buenos Aires

Congreso; XXIV ANNUAL MEETING OF THE ARGENTINEAN SOCIETY OF BIOLOGY (SAB); 2022

Sociedad Argentina de Biología

Adenogenesis is a critical process in the differentiation of the broad-snouted caiman oviduct. Regulation of adenogenesis depends on several molecular pathways, which, in turn, are modulated by sex steroid hormones and can be affected by exposure to endocrine-disrupting compounds (EDCs). Endosulfan (END) is a persistent organic pollutant classified as an EDC with xenoestrogenic action. Our aims were (1) to characterize changes in the oviduct epithelium and subepithelium during adenogenesis; (2) to evaluate the effects of in-ovo exposure to END (20 ppm) on these processes; and (3) to determine the circulating levels of E2 and T. In the oviduct of prepubertal juvenile female caimans (VEH and END), we established a histofunctional score and the organization of subepithelial collagen fibers, and we evaluated the gene expression of proteins involved in subepithelium remodeling (metalloproteinases and its inhibitors), intracellular adherence (CTNNB1, the gene that encodes β-catenin, and the protein itself), and induction of epithelial invagination (Wnt-7a). The histofunctional score was evaluated through the frequency of observation of tissular and cellular features indicative of oviductal differentiation. Collagen organization was quantified as the percentage of the total subepithelial width occupied by poorly organized fibers or by highly organized fibers. Gene expression was assessed by qPCR, using L8 as a housekeeping gene. Protein expression was revealed by immunohistochemistry and quantified in digitalized images. In-ovo exposure to END advanced oviductal adenogenesis, as evidenced by increased histofunctional score (VEH 14.5 ± 2.38 vs. END 19.63 ± 1.40) and supported by increased gene expression of MMP2 (VEH 3.20 ± 0.98 vs. END 6.63 ± 2.26), MMP9 (VEH 2.36 ± 0.47 vs. END 3.65 ± 0.95), TIMP1 (VEH 1.74 ± 0.17 vs. END 2.61 ± 0.24), and CTNNB1 (VEH 1.23 ± 0.35 vs. END 1.96 ± 0.53). No changes were observed in the circulating levels of E2 and T. Results (mean ± SEM) show that the molecular pathways that regulate adenogenesis and the temporal pattern of histomorphological changes of the oviduct are altered by in ovo exposure to END, which could lead to alterations in fertility.