Stimulation of litter size using an immunestimulant in commercial swine

产前死亡（胚胎死亡）是北美商业猪肉生产商的主要经济问题。大约30%至40%的正常孕体在妊娠第15天至第50天之间以两个明确的胎儿丢失波丢失。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长期努力未能显着改善商品猪的窝仔数。同样，维生素补充剂或改善均衡饮食对窝仔数的改善影响最小。我们以前的工作提供了具体的证据表明，胎儿停止和随后的死亡与母体淋巴细胞无法促进足够的血管发育，以支持所有概念的增长。这使得母体淋巴细胞成为有吸引力的治疗靶点。我们已经完成了一个成功的证明，主要试验解决这一假设，使用一个专门制定的原型化合物从Bioniche生命科学公司的动物使用。本申请旨在评价这种低成本化合物，该化合物是从成功的人类生物制剂的平台技术开发的，可使窝仔数增加3头仔猪，并大大减少了仔猪的生长。本提案的目的1是比较全身给药与子宫内输注MpRNC对母体/胎儿血管发育和窝仔数结局的影响。目的2关注MpRNC对MpRNC处理母猪所产仔猪的总体产后健康和生殖性能的影响，与对照相比。目标3的重点是评估子宫内输注MpRNC（Bioniche Life Sciences，Inc.）的安全性和毒性并确定妊娠期间给药母体和给药母体产下的仔猪是否会产生不良免疫应答。目前的研究提案有望为猪提供一种安全，易于管理的免疫刺激剂，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存活。这些研究中产生的数据对于开发MpRNC的生育力增强应用至关重要，不仅适用于猪，而且适用于其他家畜。

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.