The influence of tumor necrosis factor α (TNF) on the secretory function of bovine corpus luteum: TNF and its receptors expression during the estrous cycle

Tumor necrosis factor α (TNF) inversely regulates the function of bovine corpus luteum (CL). Whereas the low doses of TNF induce luteolysis, the high doses prolong CL lifespan and prevent luteolysis in vivo. We suggest that the varying effects of TNF may be caused by its action exerted on CL via multiple signaling pathways involving two distinct receptors: TNFR-I (responsible for induction of the cell death) and TNFR-II (implicated in cell proliferation). In the study, we determined CL expressions of TNF, TNFR-I and TNFR-II mRNAs during the bovine estrous cycle using semiquantitative RT-PCR. Specific transcripts for TNF, TNFR-I and TNFR-II were found in the CL with the highest (p<0.05) expression in the regressed CL. We also examined the TNF influence on the bovi0ne CL function in vivo. On Day 15 of the estrous cycle, cows were infused (via aorta abdom-inalis) with saline, TNF (1 or 10 μug) or analogue of prostaglandin (PG)F_2α (aPGF_2α , 500 μg; a positive control). Four hours after infusions, CLs were collected by colpotomy and luteal contents of progesterone (P₄), stable metabolites of nitric oxide (NO; nitrite/nitrate), leukotriene (LT)C ₄, luteolytic PGF_2α,and luteotropic PGE₂ were determined. Moreover, caspase-3 activity was measured in the CLs as an indicator of apoptosis induction. The luteal content of P₄ decreased (p<0.05) after infusion of 1 μg of TNF. TNF inversely affected PGs content in CL: the low dose increased (p<0.01) the PGF_2α level and the high dose increased (p<0.05) PGE₂ level. Contents of LTC ₄ and nitrite/nitrate increased (p<0.01) after the low dose of TNF. Moreover, 1 μg of TNF induced apoptosis and increased (p<0.05) caspase-3 activity in the CLs collected during the late luteal phase. In conclusion, the high expressions of TNF and TNF receptors mRNAs were observed during or just after the luteolysis. A low concentration of TNF stimulated in vivo luteolytic factors such as PGF_2α, LTC₄ and NO as well as induced apoptosis; whereas the high concentration of TNF stimulated a survival pathway in the bovine CL increasing luteal content of P₄ and PGE₂.