Nonylphenol releases arachidonic acid in rat Sertoli cells via activation of PKA and PLA2

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dc.contributor.authorValtierra, Florencia X. Santiago
dc.contributor.authorUrriola-Munoz, Paulina
dc.contributor.authorGodoy-Sepulveda, Rodrigo
dc.contributor.authorMoreno, Ricardo D.
dc.contributor.authorReyes, Juan G.
dc.contributor.authorValles, Ana S.
dc.contributor.authorOresti, Gerardo M.
dc.date.accessioned2025-01-20T16:12:47Z
dc.date.available2025-01-20T16:12:47Z
dc.date.issued2024
dc.description.abstractNonylphenol (NP), an endocrine-disrupting chemical, is an environmental contaminant, and many notorious effects on male fertility have been reported in animal models and wild-type species. Here, we evaluated the effects of NP in follicle-stimulating hormone (FSH) signal transduction pathways and lipid metabolism using an in vitro model of rat Sertoli cell (SC) primary culture. Results show that an acute (1 h) SC exposure to NP (10 mu M) increased the intra- and extra-cellular concentrations of free fatty acids (FFAs), mainly arachidonic acid (20:4n-6). Phosphatidylinositol seemed to be the major phospholipid source of this 20:4n-6 release by activation of the protein kinase A (PKA)/cytoplasmic phospholipase A2 (cPLA2) pathway. NP also increased diacylglycerols (DAG) levels and the expression (mRNA) of cyclooxygenase 2 (Cox2) and prostaglandin E2 (PGE2) levels. It is noteworthy that accumulation of lipid droplets took place after 24 h NP exposition, which was prevented by both a PKA inhibitor and a PLA2 inhibitor. Like FSH, NP triggers the release of 20:4n-6, which is a substrate for PGE2 synthesis via PKA/PLA2 activation. In addition, NP induces the formation of DAG, which could be required as a cofactor of the PKC-mediated activation of the COX2 inflammatory pathway. Our findings suggest that NP alters lipid homeostasis in SCs by inducing the activation of pro-inflammatory pathways that may trigger adverse effects in testis physiology over time. Concomitantly, the SC enhances the acylation of surplus FFAs (including 20:4n-6) in neutral lipids as a protective mechanism to shield itself from lipotoxicity and pro-inflammatory signals.
dc.fuente.origenWOS
dc.identifier.doi10.1530/REP-23-0292
dc.identifier.eissn1741-7899
dc.identifier.issn1470-1626
dc.identifier.urihttps://doi.org/10.1530/REP-23-0292
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90354
dc.identifier.wosidWOS:001271246200001
dc.issue.numero1
dc.language.isoen
dc.revistaReproduction
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNonylphenol releases arachidonic acid in rat Sertoli cells via activation of PKA and PLA2
dc.typeartículo
dc.volumen168
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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