The pesticides endosulfan and cypermethrin affect neuronal differentiation via retinoic and peroxisome proliferator receptor activity

• Brain development is highly dependent on hormonal homeostasis, hence developmental exposure to endocrine disrupting chemicals (EDCs) is of high concern. In fact, epidemiological and in vivo studies support associations between exposure to EDCs and impaired neurodevelopment. However, the existing hazard assessment of EDCs does not consider developmental neurotoxicity (DNT) prompting an urgent requirement for innovative testing and screening tools addressing endocrine disruption (ED)-induced DNT. We have previously shown the applicability of the immortalized murine neural progenitor cells, C17.2 cells, for addressing ED-DNT. We evidenced decreased neurite outgrowth and branching when the cells were exposed to the Rar, Rxr or Pparβ/δ agonists, and concluded that this is a suitable model for the evaluation of ED-induced DNT for chemicals disrupting Rar, Rxr or Pparβ/δ signalling. In this study we further validated the C17.2 method by testing the effects of 25 EDCs on the same neuronal morphology endpoints as reported in the previous paper. Out of the tested chemicals, endosulfan and cypermethrin decreased, while benzyl butyl phthalate (BBzP) increased neurite outgrowth and branching. We proceeded to evaluate whether these effects were mediated by Rar, Rxr or Ppar β/δ agonism. The neuronal morphology effects of endosulfan and cypermethrin were rescued by co-exposures Rar and Rxr antagonists, and partially rescued by the Ppar β/δ antagonist indicating a common mechanism. With this approach, we have identified that the C17.2 cells can be used as an in vitro model to address ED-induced DNT.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Endocrine disruptors

Developmental neurotoxicity

Retinoids

Peroxisome proliferator-activated receptor

in vitro testing

Biologi

Biology

Biology with specialization in Environmental Toxicology

Biologi med inriktning mot miljötoxikologi

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)