Is Interleukin 1α a Luteotropic or Luteolytic Agent in Cattle?

Abstract

The genes for interleukin (IL)1α and its functional receptors are present in the bovine female reproductive tract during the estrous cycle. IL1α stimulates prostaglandin (PG) production in cultured bovine endometrial cells. The target of IL1α for stimulating both luteotropic PGE2 and luteolytic PGF2α production is the stromal cells. The stimulatory effect of IL1α on PG production is mediated by differently modulating of phospholipase A2 and expression of respective PG synthases in the stromal cells. Moreover, IL1α stimulates PG secretion in the steroidogenic cells of bovine corpus luteum (CL) in vitro without any effect on progesterone (P4) production. However, physiological meaning of these findings is unclear. To determine physiological role of IL1α, it's influence on PG secretion by the cultured bovine endometrial tissues obtained from the cyclic or early pregnant cows, and the effect of IL1α on PG, progesterone (P4) output and the CL lifespan in vivo were examined. In Exp. 1, effects of IL1α with/without an embryonic signal (interferone-τ, INFτ) on PG secretion by cultured endometrial tissues were examined. Explants of endometrium (30-40 mg) obtained from the cows at Day 16/17 of the estrous cycle (Group 1; n=7) or early pregnancy (Day 16/17 after insemination, Group 2; n=6) were stimulated for 18-h with: saline (control), TNFα (10 ng/ml), IL1α (10 ng/ml), IFNα(30 ng/ml) or IL1α combination with IFNτ. Concentrations of PGE2 and PGF2α in the culture medium were measured by EIA. IL1α alone stimulated secretion of luteotropic PGE2 in endometrial tissues of both Group 1 and Group 2 (more than 200% of the control, P<0.01). IL1α also stimulated luteolytic PGF2α output from endometrial explants, but only during the late luteal phase (150%, P<0.05). This stimulatory effect of IL1α on PGF2α secretion was inhibited by INFτ (P<0.05). Moreover, IFNτ augmented the stimulatory effect of IL1a on PGE2 secretion (P<0.05). In Exp. 2, the effects of IL1α administrated into the uterine lumen on PGF2α, PGE2 and P4 secretions, and on the lifespan of the CL were determined in vivo. Saline (5 ml, control; n=5) or IL1α at different doses: 0,001 (n=3); 0.01 (n=5); 0.1 (n=5); 1 (n= 5) and 10 μg (n=3) in 5 ml of saline were applied at Day 16 of the estrous cycle. P4, PGE2 and PGFM (stable metabolite of PGF2α) concentrations in peripheral blood were measured by EIA. IL1α at doses 0.1 and 1 μg stimulated P4 and PGE2 output (P<0.01), and simultaneously inhibited spontaneous luteolysis with prolonging the lifespan of CL (P<0.01). Although only the lowest dose of IL1α (0.001 μg) caused a temporal increase in PGFM concentration during the experiment (until 12-h after application; P<0.05), any doses of IL1α had effect on the CL lifespan. Concluding, IL1α may play some important autocrine or paracrine roles in regulating PG production in the endometrium and CL during the estrous cycle and early pregnancy in cattle. IL1α increased P4 and luteotropic PGE2 concentrations in blood plasma that may result in appropriate development and function of the bovine CL during the estrous cycle. These luteotropic effects of IL1α during pregnancy may support the early embryo development and implantation, and may play a supporting role in the maternal recognition of pregnancy in cattle. Supported by Grant 2P06K02529.