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Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

López‐Arellano, Patricia, López‐Arellano, Keila, Luna, Jaquelinne, Flores, Diana, Jiménez‐Salazar, Javier, Gavia, Graciela, Teteltitla, Mario, Rodríguez, Juan José, Domínguez, Alejandro, Casas, Eduardo, Bahena, Ivan, Betancourt, Miguel, González, Cristina, Ducolomb, Yvonne, Bonilla, Edmundo
Environmental toxicology 2019 v.34 no.1 pp. 92-98
apoptosis, cell communication, female fertility, females, follicular fluid, gap junctions, hepatocytes, lethal concentration 50, mice, necrosis, occupational exposure, oocytes, oxidative stress, perfluorocarbons, perfluorooctanoic acid, reactive oxygen species, staining, toxicity, women
Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon–fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied. Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC₅₀ = 112.8 μM), as evaluated with Annexin‐V‐Alexa 508 in combination with BOBO‐1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH‐DA, increased significantly in fetal ovaries exposed to ¼ LC₅₀ (28.2 μM, a noncytotoxic and relevant occupational exposure concentration) and LC₅₀ PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells‐oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.