Immunophysiology of the uterus in cyclic ewes

Abstract

Uterine infections in farm animals are a serious problem in developing countries. Several factors are involved in regulating susceptibility of animals to infections. The experiments conducted with ewes for this dissertation aimed to 1) Investigate the hormonal regulation of uterine immune responses to infections during different stages of the estrous cycle (Exp. 1), and 2) Investigate the ability of uterine proteins, collected during different stages of the estrous cycle, to regulate lymphocyte activity in vitro (Exp. 2). Experiment 1 was a 2 X 2 factorial design, with stage of estrous cycle (follicular vs luteal) and treatment (bacteria vs saline) as main effects. Escherichia coli and A.pyogenes were used for uterine inoculations. Blood was collected, via catheters inserted into the vena cava, twice daily for six days. Estrogens, progesterone, PGF_2α, and PGE₂, were measured in blood, lymphocyte (T- and B) activities were assessed in vitro, and leukocyte differential counts were made. Follicular-phase ewes, under predominance of estrogens, had increased vena caval percentage of lymphocytes and greater T- and B-lymphocyte activity in response to mitogens than luteal-phase ewes, under predominance of progesterone. Concentration of PGF_2α increased in response to bacterial inoculation, but PGE₂ did not affect by treatment. Experiment 2 was a split-plot design, with stage of estrous cycle and status of ewes (intact vs ovariectomized) as main effects. The amount of total proteins in uterine flushings from intact ewes was greater than that from ovariectomized ewes. Two protein peaks were separated on a Sephacryl S-100 column. Peak one had an estimated size of ≤ 1 X 10⁵ Da, and peak two had an estimated size of 12.7 X 10³ Da. Small concentrations of peak one protein from intact follicular-phase ewes enhanced activity of T-lymphocytes in response to mitogen, whereas peak two protein from intact luteal-phase ewes suppressed T-lymphocyte activity. Peaks one and two from ovariectomized ewes suppressed T-lymphocyte activity. In conclusion, the uterus of ewes under the influence of estrogens had enhanced immune capability and was able to secrete immunostimulatory proteins. Ewes under the influence of progesterone had suppressed uterine immune functions.