Cytotoxicity and Aromatase (CYP19) Activity Modulation by Organochlorines in Human Placental JEG-3 and JAR Choriocarcinoma Cells

Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells

“…Our results also confirmed and extended our previous study on the human placental JEG3 cell line (Richard et al 2005). This cell line is considered to be a useful model for examining placental toxicity (Letcher et al 1999). Our studies also revealed that the embryonic cells are more sensitive than the placental ones.…”

“…Among the two lines, the 293 cells have proven to be very suitable to estimate hormonal activity for xenobiotics after transfection (Kuiper et al 1998). In contrast, JEG3 cells present natural aromatase activity and are also considered a useful model to examine placental toxicity (Letcher et al 1999). These cell lines may be even less sensitive to xenobiotics than primary cultures (LÕAzou et al 2005); in this case, the effects measured could well be an indication of human placental toxicity in vivo, if sufficient contamination occurs, because the phenomena appear to be amplified with time in cells.…”

The effects of transovarian exposure to <i>p,p’</i>-DDT and <i>p,p’</i>-DDE on avian reproduction using Japanese quails

“…In female fathead minnows transcriptions of the cyp19a1a, cyp17 and follicle stimulating hormone receptor (fshr) genes increased at the same time, and in B[a]P exposed rats serum and pituitary gland levels of luteinizing hormone (LH) increased. Because p,p'-DDT and B[a]P but not p,p'-DDE were reported to inhibit aromatase activity in cell culture (Letcher et al, 1999;Sanderson et al, 2002), in vivo depletion of estra-FSH production in the pituitary gland and enhance transcription of the CYP11A1 gene that codes for the cholesterol side-chain cleavage enzyme and is thus a starting point in steroid hormone synthesis. The aromatase p,p'-DDT (Sanderson et al, 2002), and so the p,p'-DDT adminis-tered here is likely to exert its anti-estrogenic effect in the developing embryos.…”

In Vitro Models in Endocrine Disruptor Screening

“…The aromatase assay has been used in the assessment of the activity of numerous agents including pesticides like atrazine, diuron, and fenarimol (Andersen et al 2002;Heneweer et al 2004;Vinggaard et al 2000), organochlorines, polychlorinated biphenyls, and TCDD (Drenth et al 1998;Letcher et al 1999;Sanderson et al 2002), organotin (Cooke 2002;Nakanishi et al 2002), and phytoestrogens (Pelissero et al 1996). These studies have utilized cell-free enzymatic preparations from both human placenta and recombinant sources (Andersen et al 2002;Stresser et al 2000), primary cultures of hepatocytes and Leydig cells (Biegel et al 1995;Liu et al 1996), and immortalized JEG-3, Jar, and H295R chorio-and adrenocortical carcinoma cell culture systems (Letcher et al 1999;Vinggaard et al 2000).…”

“…These studies have utilized cell-free enzymatic preparations from both human placenta and recombinant sources (Andersen et al 2002;Stresser et al 2000), primary cultures of hepatocytes and Leydig cells (Biegel et al 1995;Liu et al 1996), and immortalized JEG-3, Jar, and H295R chorio-and adrenocortical carcinoma cell culture systems (Letcher et al 1999;Vinggaard et al 2000). Although the authors of studies using the cell culture models (Letcher et al 1999;Sanderson et al 2002) have remarked as to the negative impact of cytotoxicity on their potential utility in this assay, the ability to discriminate true direct impact of a test material on aromatase activity, rather than reduced activity via impairment of cellular function, is a critical issue in the implementation of a validated screening methodology.…”