To determine the physiological significance of tumor necrosis factor α (TNFα) in the regulation of luteolytic prostaglandin (PG) F2α release by the b

Tumor necrosis factor α (TNFα) has been shown to be a potent stimulator of prostaglandin (PG) F_2α secretion in the bovine endometrium. The aims of the present study were to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGF_2α in response to TNFα, and the intracellular mechanisms of TNFα action. Cultured bovine epithelial and stromal cells were exposed to TNFα (0.006–6 nM) or oxytocin (100 nM) for 4 h. TNFα resulted in a dose-dependent increase of PGF_2α production in the stromal cells (P < 0.001) but not in the epithelial cells. On the other hand, oxytocin stimulated PGF_2α output in the epithelial cells but not in the stromal cells. When the stromal cells were incubated for 24 h with TNFα and inhibitors of phospholipase (PL) C or PLA₂, only PLA₂ inhibitor completely stopped the actions of TNFα (P < 0.001). When the stromal cells were exposed to TNFα and arachidonic acid, the action of TNFα was augmented (P < 0.001). When the stromal cells were incubated for 24 h with a nitric oxide (NO) donor (S-NAP), S-NAP stimulated the PGF_2α production dose-dependently. Although an NO synthase (NOS) inhibitor (l-NAME) reduced TNFα-stimulated PGF_2α production, an inhibitor of phosphodiesterase augmented the actions of TNFα and S-NAP (P < 0.05). The overall results indicate that the target of TNFα for stimulation of PGF_2α production in cattle is the endometrial stromal cells, and that the actions of TNFα are mediated via the activation of PLA₂ and arachidonic acid conversion. Moreover, TNFα may exert a stimulatory effect on PGF_2α production via the induction of NOS and the subsequent NO-cGMP formation.

Phytoestrogens, polyphenolic compounds derived from plants, are more and more common constituents of human and animal diets. In most of the cases, these chemicals are much less potent than endogenous estrogens but exert their biological effects via similar mechanisms of action. The most common source of phytoestrogen exposure to humans as well as ruminants is soybean-derived foods that are rich in the isoflavones genistein and daidzein being metabolized in the digestive tract to even more potent metabolites—para-ethyl-phenol and equol. Phytoestrogens have recently come into considerable interest due to the increasing information on their adverse effects in human and animal reproduction, increasing the number of people substituting animal proteins with plant-derived proteins. Finally, the soybean becomes the main source of protein in animal fodder because of an absolute prohibition of bone meal use for animal feeding in 1995 in Europe. The review describes how exposure of soybean-derived phytoestrogens can have adverse effects on reproductive performance in female adults.

The objective of this study was to determine whether nitric oxide (NO) is produced locally in the bovine corpus luteum (CL) and whether NO mediates p

Progesterone is suggested to be a suppressor of apoptosis in bovine luteal cells. Fas antigen (Fas) is a cell surface receptor that triggers apoptosis in sensitive cells. Furthermore, apoptosis is known to be controlled by the bcl-2 gene/protein family and caspases. This study was undertaken to determine whether intraluteal progesterone (P4) is involved in Fas L–mediated luteal cell death in the bovine corpus luteum (CL) in vitro. Moreover, we studied whether an antagonist of P4 influences gene expression of the bcl-2 family and caspase-3 and the activity of caspase-3 in the bovine CL. Luteal cells obtained from the cows in the midluteal phase of the estrous cycle (Days 8–12 of the cycle) were exposed to a specific P4 antagonist (onapristone [OP], 10⁻⁴ M) with or without 100 ng/ml Fas L. Although Fas L alone did not show a cytotoxic effect, treatment of the cells with OP alone or in combination with Fas L resulted in killing of 30% and 45% of the cells, respectively (P < 0.05). DNA fragmentation was observed in the cells treated with Fas L in the presence of OP. The inhibition of P4 action by OP increased the expression of Fas mRNA (P < 0.01); however, it did not affect bax or bcl-2 mRNA expression (P > 0.05). Moreover, OP stimulated expression of caspase-3 mRNA (P < 0.01). The overall results indirectly show that intraluteal P4 suppresses apoptosis in bovine luteal cells through the inhibition of Fas and caspase-3 mRNA expression and inhibition of caspase-3 activation.