Abstract
Toxicological studies have revealed that DEHP exposure during pregnancy may induce developmental disorders, especially in male offspring, leading to morphological and functional alterations in the reproductive system by mechanisms that should be investigated. Thus, the aim of this work was to analyze the testicular toxicity induced by an environmentally relevant DEHP dose during development and its impact on FLNA, a protein that participates in the blood-testis barrier assembly. We used male Wistar rats exposed to DEHP during pregnancy and lactation. The results showed that DEHP exposure during development and lactation increased body weight, decreased gonadal weight and shortened anogenital distance. This phthalate induced morphological changes in the testis, suggestive of hypospermatogenesis. DEHP exposure decreased the number of FLNA positive cells and the expression of FLNA and claudin-1 in prepubertal testes. Furthermore, DEHP inhibited FLNA and claudin-1 protein expression in adult male rats. These results indicated that exposure to DEHP during gestation and lactation perturbed testis development and suggested that FLNA is a target protein of DEHP, possibly contributing to the phthalate-induced damage on BTB.
Highlights
Exposure to DEHP altered body weight, gonadal weight and anogenital distance.
Perinatal DEHP declined FLNA expression in prepubertal and adult rat testis.
DEHP exposure induced degenerative morphological alterations in the seminiferous tubules.
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Acknowledgements
We thank Ms. Veronica Diaz for her support in the care and treatment of the animals and Ms. Sofia Rossetto for her excellent technical assistance. This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, KB1 11220200102210CO), Fondos para la Investigación Científica y Tecnológica (PICT 2016–0042 and PICT 2020–2179), and Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (Nº 33620180100675CB).
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All authors contributed to this work, reviewed, and approved the manuscript for submission. PP and JT performed and interpreted the flow cytometer, histology, and immunohistochemical results, and wrote the manuscript. VNC performed the western blotting technique. FV, JHM, and VNC performed the practical part of immunohistochemical analysis, collected data, and wrote the methods for histological examination. PP and JT performed the statistical analysis of morphometry results. VC and MP provided reagents/materials for testosterone detection. SG conceptualized the study, provided supervision, interpreted the data, acquired funding, and wrote and edited the manuscript.
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Pérez, P.A., Toledo, J., Vitellini, F. et al. Environmentally relevant DEHP exposure during gestational and lactational period inhibits filamin a testicular expression. J Mol Histol 54, 509–520 (2023). https://doi.org/10.1007/s10735-023-10144-7
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DOI: https://doi.org/10.1007/s10735-023-10144-7