Six experiments were conducted to determine the mechanism of action of exogenous PGF2alpha on the clearance of uterine infections in sheep and pigs. The first two experiments were designed to characterize the uterine immune response to bacterial infection under progesterone dominance in pigs. The uterine immune response to infections seems to change with parity. This is probably an artifact of increased number of bacterial exposures; therefore, the third experiment was designed to evaluate the uterine immune response to multiple intrauterine bacterial inoculations. Experiments 4, 5, and 6 were designed to evaluate the effects of endogenous and exogenous PGF2alpha on the uterine immune response to uterine infections in sheep and pigs. Injections with Lutalyse (PGF2alpha analogue) during the luteal phase in sheep causes luteolysis; therefore, it impossible to evaluate the effects of Lutalyse independently of luteolysis. In order to cause an endogenous release of PGF2alpha without causing luteolysis in sheep a PGF2alpha secretagogue (oxytocin) was used in Exp. 5. And in Exp. 6, we were able to evaluate the effects of Lutalyse independently of luteolysis using pigs as a model. From these six experiments we concluded that during periods of estrogen dominance, the uterine immune system is up-regulated, and therefore, infections do not develop after intrauterine inoculation with bacteria, during periods of progesterone dominance, the uterine immune system is down-regulated, and, therefore, infections develop after intrauterine inoculation with bacteria, and stimulation of the uterus with PGF2alpha or oxytocin independently of luteolysis up-regulates the uterine immune. / Ph. D.

The uterine immune system is down regulated when exposed to P4. Five experiments were conducted to determine the in vivo and in vitro role(s) of P4 and prostaglandins in immune function(s) associated with uterine infections. In Exp. 1, postpartum ewes (d 0 = parturition) were supplemented with either OIL or P4 (beginning on d 10) or were SHAM or OVEX. Vena caval blood and lymphocytes were collected on d 14, and 16 to 19. All ewes received intrauterine inoculations of bacteria on d 15 and uteri were collected on d 20. Ewes receiving P4 developed infections. Lymphocytes were incubated with mitogens, PGE2, indomethacin (INDO; a PG synthesis inhibitor) or both in a 3 x 2 x 2 arrangement. Concanavalin A-stimulated blastogenesis in P4-OVEX ewes and PGE2 and PGE2+INDO treated lymphocytes was inhibited (P < .05). Cyclic ewes in their follicular or luteal phase received either intrauterine inoculations of saline or bacteria, vena caval blood was collected for 3 d, and uteri were collected. Lymphocytes were incubated with mitogens, PGE2 (Exp. 2), PGF2alpha (Exp. 3) and(or) INDO in a 3 x 2 x 2 arrangement. Only luteal phase ewes that received bacteria developed infections. In Exp. 2, Con A- and LPS-stimulated blastogenesis was greater for luteal than for follicular phase ewes. T lymphocyte proliferation was inhibited in ewes inoculated with bacteria. T lymphocyte proliferation tended to be higher (P = .09) when incubated with INDO. In Exp. 3, T lymphocyte proliferation in response to PGF2alpha was greater for follicular than for luteal phase ewes. Neutrophils were lower in ewes inoculted with bacteria. In Exp. 4 and 5, uteri of luteal-phase (d 6) ewes were inoculated with bacteria. Ewes received either 15 mg of Lutalyse or saline on d 9, and uteri were collected on d 11. Lutalyse reduced P4, tended to decrease neutrophils, allowed ewes to clear infections, and had no effect on blastogenesis. Methods for modulating uterine prostaglandins seem to reduce susceptibility to uterine infections. / Ph. D.

Incidences of uterine infections in dairy cattle are high between parturition and Day 21 postpartum. Dairy cows with uterine infections are at risk for prolonged periods of days open and multiple services before becoming pregnant. Neutrophils are the first wave of immune system defense against uterine contamination. Neutrophil function seems to be mediated by reproductive hormones and good uterine health is related to properly functioning neutrophils. To elucidate the interaction between reproductive hormones, neutrophils and uterine health in dairy cows the objectives of this research were to evaluate: 1) changes in circulating white blood cell populations during the estrous cycle, 2) the effects of prostaglandin F₂[subscript α](PGF₂[subscript α]) on circulating white blood cell populations and 3) the effects of a two-injection PGF₂[subscript α] regimen on uterine neutrophil and bacterial populations and numbers of days open and services per conception. In the first experiment, the effect of stage of the estrous cycle on plasma neutrophil numbers was evaluated. Neutrophils were observed throughout the entire estrous cycle and numbers were greatest (P<0.05) on Day 14 (mid-cycle), when the corpus luteum was the dominant ovarian structure and plasma progesterone was at its acme. In the second experiment, plasma neutrophil numbers were examined in cows after injections of saline or the PGF₂[subscript α] pharmaceutical product, Lutalyse. Compared to saline, numbers of neutrophils were greater (P<0.05) 4 and 8 hr after Lutalyse injection. In the third experiment, neutrophil numbers were examined after injections of saline, Lutalyse or the PGF₂[subscript α] analog, Estrumate. Compared to saline, numbers of neutrophils did not differ (P>0.10) from cows injected with Lutalyse or Estrumate. In the fourth experiment, uterine bacterial populations and numbers of neutrophils were quantified in cows treated with Lutalyse or saline on Days 0 and 14 or 14 and 28 postpartum. Compared to saline, Lutalyse treatment decreased (P<0.05) total bacteria present in the uterus and increased (P<0.05) the number of uterine neutrophils. In experiment five, numbers of days open and services per conception were evaluated in cows treated with Lutalyse or saline on Days 0 and 14 or 14 and 28 postpartum. Compared to saline, Lutalyse decreased days open (154.7 ± 14.1 vs. 120.1 ± 7.9 days, respectively; P<0.05) and services per conception (3.0 ± 0.4 vs. 2.3 ± 0.2 services, respectively; P=0.09). These results suggest PGF₂[subscript α] treatment can increase neutrophil and depress bacterial cell populations in favor of the dairy cow's uterine health and may explain why fertility is improved when PGF₂α is administered early in the postpartum period. / Graduation date: 2012