Mechanisms regulating porcine fetal survival and outcomes from therapeutic intervention

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Prenatal mortality is an economic concern for commercial pork producers in North America. Twenty to 30% of fetuses are lost between gestation days (gd)12 and 30 and another 10 to 15% later in gestation. Placental efficiency and uterine capacity are the parameters identified as having the greatest influences on porcine fetal survival but selection strategies targeting these traits have not significantly improved litter sizes. Greater definition of the physiological and immunological interactions between the mother's uterine lining and embryos as they attach (gd!2) is needed to enable new ways of promoting developmental success of more embryos. The proposed research addresses improved molecular understanding of the peri-attachment porcine maternal-fetal interface and evaluation of a novel therapeutic approach. We established a highly successful technique for quantitative comparative studies between arresting and healthy littermates of 5 distinct tissue types within individual attachment sites from gd!9. Aim 1 of the proposal seeks the time at which heterogeneity in gene expression significant enough to alter viability is established between littermates (ie before gd!9) and if this can be modified by adjuvant treatment at first estrus. Aim 2 will characterize uterine maternal dendritic cells and their interactions with endometrial lymphocytes. Aim 3 will address cellular and cytokine outcomes within arresting attachment sites due to reduction in the CC chemokine decoy molecule D6. Ontario Pork and Bioniche Life Sciences, Inc. have committed funding support. Outcomes from this proposal should provide new insights into control of mechanisms that regulate success or failure of pregnancy in pigs and provide opportunity for economic gain in the food production and manufacturing sectors of the Canadian economy. Information from these studies should also be of value for other livestock species and for humans with pregnancy complications, infertility or using assisted reproductive technologies such as in vitro fertilization an embryo transfer.