TNF-Alpha and TGF-Beta Signaling Cascades are Associated with the Changes in the Mode of Action of Estradiol in the Rat Oviduct

In the rat, administration of 2-metoxyestardiol (2ME) accelerates oviductal egg transport in cyclic but not in pregnant rats. This paradoxical effect is consequence of the silencing of a nongenomic pathway of E2 induced by mating in the oviduct. Since mating induces an inflammatory response in the female genital tract we propose that some cytokines could mediate this change in the mode of action of E2. Herein we determined the effects of mating on TNF-α or TGF-β signaling in the rat oviduct. Rats on the night of proestrus were kept isolated as non-mated group or caged with fertile males in the midnight of estrus for 30 minutes. Mating was verified by the presence of spermatozoa in vaginal smear and at 1, 3 or 6 hours post-mating, rats were autopsied to obtain the oviductal fluid and the serun in order to determine the local and systemic levels of TNF-α or TGF-β by ELISA. Furthermore, we examined the mRNA and protein levels of the TNF-α receptors, Tnfrsf1a, Tnfrsf1b and TGF-β receptor, Tgfbr3 in the endosalpinx and myosalpinx by Real-time PCR and Western blot. TNF-α dramatically increased in the oviductal fluid while TGF-β decreased in the serum only at 3 hours post-mating. Levels of mRNA of Tnfrsf1a or Tnfrsf1b were not affected by mating in endosalpinx and myosalpinx although Tnfrs1a protein increased in the myosalpinx at 1 hour post-mating. In the endosalpinx Tgfbr3 increased at 3h in non-mated rats while this transcript was increased at 1h post-mating. In the myosalpinx, protein levels of Tgfbr3 decreased at 3 hours in non-mated rats while this receptor was increased at 1 and 3 h and decreased at 6 h post-mating. We conclude that the effect of mating on the silencing of the E2 non-genomic pathway is associated with changes in the components of the TNF-α and TGF-β signaling suggesting that these cytokines modulate the mode of action of E2 in the oviduct.