Mechanisms regulating porcine fetal survival and outcomes from therapeutic intervention

对于北美的商业猪肉生产商来说，产前死亡率是一个经济问题。20%到30%的胎儿在怀孕12天到30天之间丢失，另有10%到15%的胎儿在怀孕后期丢失。胎盘效率和子宫容量是被认为对猪胎儿存活率影响最大的参数，但针对这些性状的选择策略并没有显着提高产仔数。需要更好地定义母亲子宫衬里和胚胎附着时的生理和免疫相互作用(gd！2)，以实现促进更多胚胎发育成功的新方法。这项拟议的研究致力于提高对猪周围附着的母胎界面的分子理解，并评估一种新的治疗方法。我们建立了一种非常成功的技术，用于从GD9开始在个体附着部位内对5种不同组织类型的停产和健康窝产仔进行定量比较研究。建议的目标1寻求在不同的窝龄之间(即在GD9之前)建立足以改变生存能力的基因表达异质性的时间，以及这种异质性是否可以通过第一发情时的辅助治疗来改变。目的2研究子宫母细胞树突状细胞及其与子宫内膜淋巴细胞的相互作用。AIM 3将解决由于CC趋化因子诱饵分子D6减少而阻止附着部位的细胞和细胞因子结果。安大略省猪肉公司和Bioniche生命科学公司已承诺提供资金支持。这项提案的结果应该为控制猪怀孕成败的机制提供新的见解，并为加拿大经济的食品生产和制造业提供经济收益的机会。这些研究的信息对其他牲畜物种和有妊娠并发症、不孕不育或使用体外受精和胚胎移植等辅助生殖技术的人类也应该有价值。

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.