Effects of DEHP phthalate on the expression of proteins that are part of the blood-testis barrier.

VITELLINI, FACUNDO; PÉREZ, PABLO ANÍBAL; TOLEDO, JONATHAN; SILVA, TAMARA YOHANA; GUTIERREZ, SILVINA

Cordoba

Jornada; Jornada de Investigación cientifica de la Facultad de Ciencias Médicas UNC; 2023

Facultad de Ciencias Médicas UNC

Toxicological studies have revealed that exposure to an anthropogenic environmental contaminant, di-2-ethylhexyl phthalate (DEHP), during development induces both morphological and functional alterations of the reproductive system through mechanisms that are not yet fully understood. This has prompted an analysis of the effects of DEHP on testicular development, involving an evaluation of Filamin A (FLNA) expression, a protein integral to the assembly of the blood-testis barrier (BTB), and claudin-1, a protein pivotal for the structural integrity of this barrier.Male Wistar rats were exposed to either 200 μg/ml of DEHP (the standard exposure dose) or corn oil (used as controls) (n=15/group) throughout gestation and lactation, following a maternal exposure model. The animals were sacrificed at 21 and 75 postnatal days (during the prepubertal and adulthood periods, respectively), and the testicles were processed for ultrastructural analysis of germ cells using transmission electron microscopy, detection of FLNA through immunohistochemistry, quantification of FLNA-expressing cell numbers using flow cytometry, and analysis of claudin-1 via western blot.Data analysis involved the application of Analysis of Variance (ANOVA), followed by Tukey´s test to identify differences in means.The results revealed that exposure to DEHP during development and lactation led to a reduction in the number of testicular cells expressing FLNA, accompanied by a decrease in the expression of FLNA and claudin-1 proteins within prepubertal animal testicles. In adulthood, DEHP inhibited the expression of FLNA and claudin-1 proteins, consequently inducing disorganization of the maturation layers of the germinal epithelium, along with degenerative alterations at the ultrastructural level of the germinal progeny.These results indicate that exposure to DEHP during gestation and lactation affects testicular development, disrupting the assembly and structure of the blood-testis barrier (BTB), providing new insights into the impact of a pervasive endocrine disruptor and the triggering mechanism on the testis.