Dose-and-time dependent effect of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) on progesterone secretion by porcine luteal cells cultured in vitro

In the current study, to characterize TCDD action during luteal phase of th e ovarian cycle, the direct effect of TCDD was investigated in vitro using a system of monolayer cell culture. Luteal cells isolated from mid-developing corpora lutea were cultured with four different doses of TCDD (0.1, 1.0, 10.0 and 100 nM). The dose of 0.1nM TCDD had no effect on progesterone (P4) secretion by luteal cells while th e doses of 10nM and 100nM in the same, statistically significant manner dec reased P4 secretion (p<0.05). The inhibitory effect of TCDD was dependent n ot only on doses by also on experimental conditions. In cells treated every day for 72 hrs of culture with 0.1nM TCDD, P4 secretion was 71% of basal s ecretion. 100nM TCDD added only at the beginning of the culture and nor rep eated when medium was changed every 24 hrs decreased P4 secretion to 81.8% of basal secretion. The most inhibitory effect was observed in experiments in which 100nM TCDD was added at the beginning of the culture and medium wa s not changed for 72 hrs. Secretion of P4 was only 33.9% of that by control cultures. In order to show the time-dependent response to TCDD in terms of P4 secreti on, luteal cells were cultured for 24,48, 72 hrs with 0.1 and 100nM TCDD. 8 5%, 75% and 72% of basal progesterone secretion was noted after 24, 48 and 72h respectively in 0.1nM TCDD-treated cells. In 100nM TCDD treated cells t he decrease of progesterone secretion was 57%, 67% and 82% of basal secreti on after 24, 48 and 72 hrs of culture. These experiments suggest that TCDD by suppressing progesterone secretion b y corpora lutea can cause adverse reproductive effects such as early pregna ncy failure. Endocrine disrupters that interfere with progesterone producti on can act as abortifacients.