Identification of cell-surface receptors associated with 6-PPD quinone-induced reproductive toxicity in Caenorhabditis elegans after long-term and low-dose exposure: A primordial response including sword effect and shield effect

Abstract

6-PPD quinone (6-PPDQ) has been frequently detected in different environmental matrices and widely identified as causing reproductive toxicity. However, the molecular initiation events of the reproductive toxicity induced by 6-PPDQ exposure, the primordial response, remain largely unknown. This study focused on investigating the primordial response induced by cell-surface receptors localized in the epidermis and intestine of 6-PPDQ exposure on reproductive toxicity. 7 cell-surface receptors were recognized to control the 6-PPDQ-induced reproductive toxicity. The epidermal cell-surface receptors (DCAR-1 and DAF-4) mainly mediated the primordial response by enhancing epidermal innate immune response or reproductive aging, and the intestinal cell-surface receptors (SER-5, FSHR-1, GON-2, DAF-2, and EGL-15) mainly mediated the primordial response by inducing oxidative stress or intestinal innate immune response. In epidermis, DAF-4 mediated “sword effect” and DCAR-1 mediated “shield effect” in response to the primordial response of the 6-PPDQ-induced reproductive toxicity. In intestine, SER-5, DAF-2, EGL-15, and GON-2 mediated “sword effect” and FSHR-1 mediated “shield effect” in response to the primordial response of the 6-PPDQ-induced reproductive toxicity. This study provides the “first station” of the effect of long-time 6-PPDQ exposure at environmentally relevant concentrations on reproductive capacity in organisms.