Effects of exogenous tumour necrosis factor-alpha on the secretory function of the bovine reproductive tract depend on tumour necrosis factor-alpha concentrations.

The aim of study was to correlate tumour necrosis factor-alpha (TNF) infused doses used with the TNF concentrations achieved and with the secretory function of both the ovary and the uterus in cows. We evaluated the concentrations of progesterone (P4), prostaglandin (PG)F(2alpha), PGE(2) nitric oxide (NO) and TNF in the jugular vein and vena cava caudalis as parameters of exogenous TNF action on the female reproductive tract. Aortae abdominalis of cows (n = 18) were infused with saline or two doses of TNF (luteolytic--1 microg or luteotrophic--10 microg). In the peripheral blood, 1 microg TNF concentrations achieved within the range of 30-45 pg/ml, and 10 microg TNF provoked a sharp increase in achieved concentrations at a range of 250-450 pg/mL). The TNF concentrations achieved in vena cava caudalis were five to six times higher than that in peripheral blood (p < 0.001). One microgram TNF increased PGF(2alpha) and NO (p < 0.001) and decreased P4 (p < 0.05). The higher TNF dose stimulated P4 and PGE(2) (p < 0.01). TNF infusion at luteolytic dose achieved its concentrations at the physiological range previously observed in cows. Luteotrophic TNF dose achieved the concentrations in vena cava caudalis that are much higher than physiological level and were previously noted in pathological circumstances (i.e. mastitis, metritis).

Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium during the estrous cycle.

Interleukin (IL)-1 has been suggested to participate in regulation of many reproductive functions. To investigate the possible role of IL-1alpha as a local regulator in bovine endometrium, we determined the effects of IL-1alpha on prostaglandin (PG) E2 and PGF(2alpha) output by the bovine endometrium at different stages of the estrous cycle. The expressions of IL-1alpha and IL-1 receptor type 1 (IL-1RT1) mRNA in bovine endometrium were also studied. Bovine uteri were classified into six stages (estrus: day 0; early luteal: days 2-3; developing luteal: days 5-6; mid luteal: days 8-12; late luteal: days 15-17; and follicular: days 19-21). After 1h of pre-incubation, endometrial tissues (20-30mg) were exposed to 0 or 10ng/ml IL-1alpha for 4h. IL-1alpha significantly stimulated PGE2 output throughout the luteal stages, with the highest response during the mid luteal stage, while it did not stimulate PGE2 output during the estrus and the follicular stage. On the other hand, IL-1alpha significantly enhanced PGF(2alpha) output throughout the estrous cycle except in the endometrium from the mid luteal stage, with the highest response at the follicular stage (P<0.001). The treatment of endometrial tissue with IL-1alpha resulted in an increase of the PGE2:PGF(2alpha) ratio at the mid luteal stage, and in a decrease during the late luteal and follicular stages of the estrous cycle. A semiquantitative reverse transcription-polymerase chain reaction revealed that IL-1alpha and IL-1RT1 mRNA are expressed in the endometrium throughout the estrous cycle. IL-1alpha mRNA expression was greater in the early luteal stage than in the estrus, late luteal, and follicular stages (P<0.05). IL-1RT1 mRNA was greater in the late luteal stage than in the other stages (P<0.05). The overall results suggest that IL-1alpha is produced in bovine endometrium throughout the estrous cycle, and plays some roles not only in maintenance of CL, but also in luteolysis by regulating the local PGE2:PGF(2alpha) ratio in bovine endometrium during the estrous cycle.