The endocannabinoid system – Another missing link in endocrine disrupting effects of DEHP?

The phthalate DEHP is a common plasticizer which is used in plastic products and cosmetics of everyday use. During the last couple of years studies in humans and rodents as well as in cell culture models identified DEHP as an obesogen and endocrine disruptor disturbing fertility in males and females. In parallel, the endocannabinoid system has been found to be associated with the regulation of feeding and energy metabolism and a regulatory function in reproductive events. Our aim is to investigate a possible correlation between DEHP exposure and the regulation of the endocannabinoid system concerning fertility and obesogenic effects. One important link between adipose tissue and fertility is the adipokine leptin (LEP), which has been shown to regulate the central endocannabinoid system. In previous studies we found altered leptin levels in plasma of female mice fed with a DEHP-containing diet with 100% abortion in the highest dose group. To focus on peripheral/intrinsic modes of action we employed two human DEHP-treated in-vitro models (KGN: granulosa cell line, SGBS: preadipocytes) for current study. Additionally ovaries from DEHP-fed mice were investigated. The mRNA expression and the protein amount of markers like LEP and LEPR, ADIPOQ and ADIPOR2, CB1 and CB2, FAAH and GPR55 were analyzed. First data showed that DEHP-exposure of SGBS derived adipocytes led to hypertrophy of adipocytes. LEP expression and secretion as well as FAAH and CB1 expression was affected. Similar trends concerning FAAH and CB1 have been observed in the DEHP-exposed KGN granulosa cells, whereas leptin and its receptor could not be detected on the mRNA level. We conclude that DEHP may affect the endocannabinoid system by regulating the expression of elements of the endocannabinoid system such as FAAH and CB1.