Stimulation of litter size using an immunestimulant in commercial swine

产前死亡率（胚胎死亡）是北美商业猪肉生产商关注的主要经济问题。大约30%至40%的正常妊娠在妊娠第15至50天的两波明确的胎儿丢失中丢失。长期以来，采用专门针对增加子宫容量或胎盘效率的遗传选择策略的努力未能显著提高商品猪的产仔数。同样，补充维生素或改善均衡饮食对提高产仔数的影响很小。我们之前的工作提供了具体的证据，证明胎儿骤停和随后的死亡与母体淋巴细胞不能促进足够的血管发育以支持所有胎儿的生长有关。这使得母体淋巴细胞成为一个有吸引力的治疗靶点。我们已经完成了针对这一假设的主要试验的成功证明，使用了Bioniche生命科学公司专门配制的用于动物使用的原型化合物。目前的应用旨在评估这种从成功的人类生物制剂平台技术开发的低成本化合物，该化合物增加了3头仔猪的产仔数并大大减少了跑腿。本研究的目的1是比较全身给药与子宫内输注MpRNC对母体/胎儿血管发育和产仔数结局的影响。目标2的重点是MpRNC对MpRNC处理母猪与对照组所生仔猪的整体产后健康和繁殖性能的影响。目的3的重点是评估母猪授精时子宫内输注MpRNC （Bioniche Life Sciences, Inc.）的安全性和毒性，并确定在妊娠期间处理过的母猪和处理过的母猪所生的仔猪中是否会产生不良免疫反应。目前的研究计划有望为猪提供一种安全、易于管理的免疫兴奋剂，这种兴奋剂专门针对母亲的血液供应，这将在怀孕早期的关键时期刺激胎儿的存活。这些研究中产生的数据对于开发MpRNC的增殖力应用至关重要，不仅适用于猪，也适用于其他家畜。

Prenatal mortality (embryonic death) is a major economic concern for commercial pork producers in North America. Approximately 30 to 40% of normal conceptuses are lost between gestation days 15 to 50 in two well defined waves of fetal loss. Long term efforts employing genetic selection strategies specifically targeted to increasing uterine capacity or placental efficiency failed to significantly improve litter size in commercial swine. Similarly, vitamin supplements or improved balanced diet had minimal effects on litter size improvement. Our previous work provides concrete evidence that fetal arrest and subsequent death is associated with the inability of maternal lymphocytes to promote adequate blood vessel development to support growth all conceptuses. This makes maternal lymphocytes an attractive therapeutic target. We have completed a successful proof of principal trial addressing this hypothesis, using a specifically formulated prototype compound from Bioniche Life Sciences Inc for animal usage. The current application is targeted at evaluating this low cost compund developed from the platform technology of the successful human biologic that increased litter size by 3 piglets and greatly reduced runting. Aim 1 of this proposal is to compare effects of systemic administration versus intra-uterine infusion of MpRNC on maternal/fetal blood vessel development and litter size outcomes. Aim 2 is focused on Effects of MpRNC on overall postnatal health and reproductive performance of piglets born to MpRNC treated sows versus control. Aim 3 is focused on to evaluate safety and toxicity of intra-uterine infusion of MpRNC (Bioniche Life Sciences, Inc.) at the time of insemination in sows and to establish whether adverse immune response will be generated in treated dams during pregnancy and in piglets born to treated dams. The current research proposal holds the promise of a safe, easy to administer immune stimulant for pigs that specifically targets mothers blood supply, which will stimulate fetal survival during the critical time of early pregnancy. Data generated in these studies will be critical to develop a fertility enhancement application for MpRNC not just for pigs but for other domestic animals.