The effect of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL1 beta) and interleukin 6 (IL6) on endometrial PGF(2)alpha synthesis, metabolism and release in early-pregnant pigs

摘要

Cytokines produced by the porcine uterus and embryos may be involved in the regulation of endometrial prostaglandin synthesis, metabolism, and release. We studied the effect of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL1 beta) and interleukin 6 (IL6) on: 1) endometrial release of prostaglandin F(2 alpha) (PGF(2)alpha), 2) expression of the terminal enzyme of PGF(2)alpha synthesis - PGF synthase mRNA (PGFS mRNA), 3) secretion of PGF(2)alpha metabolite 13,14-dihydro-15-keto PGF(2)alpha (PGFM) by the endometrium and 4) presence and activity of endometrial NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The effects of cytokines were determined on days 10-11 and days 12-13, e.g., before and during maternal recognition of pregnancy, and on days 15-16, e.g., during the pen-implantation period and compared with its effect in cyclic gilts on corresponding days of the estrous cycle. TNF alpha did not affect endometrial release of PGR(2)alpha in pregnant and cyclic pigs. IL1 beta enhanced endometrial PGF(2)alpha release on days 12-13 and 15-16 in pregnant and cyclic pigs, respectively. IL6 increased PGF(2)alpha release mainly on days 15-16 of pregnancy. Expression of PGFS mRNA was decreased by IL1 beta on days 12-13 of pregnancy (P < 0.05) and increased in response to IL1 beta, TNF alpha and IL6 on 12-13 (P < 0.05) and 15-16 (P < 0.01) of the estrous cycle. IL1 beta increased release of PGFM in gravid pigs on days 12-13, 15-16 and in non-gravid pigs 10-11 and 15-16 of the cycle. On days 15-16 of pregnancy TNF alpha and IL6 increased endometrial secretion of PGFM. We determined that in porcine endometrium NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is present. In gravid pigs, the highest expression of endometrial 15-PGDH occurred during days 12-13 of pregnancy, while in non-gravid pigs during days 10-11 of the estrous cycle. These data provide new evidence that TNF alpha, IL1 beta, IL6 are involved in the regulation of endometrial synthesis, release and metabolism of PGF(2)alpha to protect CL during early pregnancy or to facilitate its regression in cyclic females. (C) 2012 Elsevier Inc. All rights reserved.