Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/1995
Publication Date: N/A
Interpretive Summary: Embryonic and fetal losses during pregnancy increase as the number of embryos per length of uterus increases such that increasing the number of embryos does not result in increased litter size at birth. The reason for these embryonic losses is not known. However, a possible mechanism for this loss has recently been proposed. In this hypothesis, uteroferrin, a protein secreted by the uterus which transports iron to the conceptus, may cause embryonic and fetal loss due to its ability to promote the oxidation of fats, a potentially lethal chemical reaction. Transferrin and vitamin A binding protein are two proteins which can inhibit this chemical reaction. We tested the hypothesis that for effective inhibition of uteroferrin induced lipid oxidation by these two proteins to occur, changes in uteroferrin concentration during pregnancy should be associated with similar changes in transferrin and vitamin A binding protein. Relative concentrations of the three proteins were determined during the cycle and throughout pregnancy. Both transferrin and vitamin A binding protein concentrations were strongly associated with uteroferrin concentrations in both uterine and fetal fluids, consistent with our hypothesis. These results lend support for, but do not prove, a role for transferrin and vitamin A binding protein in protecting the developing embryo/fetus from the potentially lethal fat oxidizing activity of uteroferrin. Elucidation of the mechanism of embryonic and fetal loss will allow development of strategies to increase litter size in swine.
Technical Abstract: Pregnant gilts were killed on days 7, 10, 13, 16, 19, 25, 30, 40, 50, 60, 70, 80 and 90. Cyclic gilts were killed on days 7, 10, 13 and 16. On days 7 to 19, each uterine horn was flushed with 20 ml Minimal Essential Medium (MEM). On days 25 to 90, serum and allantoic fluid samples were collected. Uterine flushings, allantoic fluid and fetal serum samples were assayed for racid phosphatase (AP, measures uteroferrin), retinol binding protein (RBP) and transferrin (TF). Endometrium from each gilt was cultured with [3H]-leucine, and conditioned medium was measured for nondialyzable radioactivity (NDR), AP, and RBP. AP, RBP and TF in uterine flushings increased markedly (p<.01) from day 7 to day 13 in both cyclic and pregnant gilts. After log transforming the data, AP was highly correlated with RBP (r=.99) and TF (r=.91, p<.01). Secretion of RBP and AP by endometrium in culture also increased (p<.01) during this period, was similar in cyclic and pregnant gilts, and was highly correlated (r=.65, p<.01). Endometrial tissue did not secrete TF. Concentrations of all three proteins in allantoic fluid increased from day 25 to day 40 and then either stabilized to day 70 followed by a decrease to day 90 (AP and TF) or decreased to day 90 (RBP). Endometrial secretion of AP and RBP increased from day 25 to 30. Then, AP increased further to day 40 and remained stable to day 60 while RBP remained stable until day 60. Both decreased from day 60 to 70, remained stable to day 80 and then increased again to day 90. The association of RBP, TF and AP during pregnancy is consistent with the hypothesis that RBP and TF may protect tissues from lipid peroxidation which may be a consequence of iron transport via secretion of uteroferrin.