Molecular mechanisms for regulation of the corpus luteum function in dairy cows: control of life and death by angiogenesis and angiolysis, and vascular tonus

奶牛黄体功能调节的分子机制：通过血管生成和血管溶解以及血管紧张来控制生命和死亡

• 批准号: 16380183
• 负责人: MIYAMOTO Akio
• 金额: $ 9.98万
• 依托单位: Obihiro University of Agriculture and Veterinary Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16380183/
• 关键词: cow; corpus luteum; angiogenesis; blood flow; luteolysis; NO; PGF2alpha; endothelial cells; 血管; 遺伝子; 細胞間コミュニケーション; 細胞・組織; 応用動物; 生理活性; 畜産学; 血管新生; プロジェステロン; カラードップラー; 血管作動性物質; 乳牛

This series of study focused on "Luteal Formation" and "Luteal Regression" in the dairy cattle from the window of "angiogenesis and angiolysis" and "vascular tonus", from the views of living animals, luteal tissues, cells, and genes using several experimental models. The major output from this study is as follows;1. Multiple injections of polyclonal antibody against major angiogenic factor VEGF or bFGF directly into the corpus luteum (CL) from immediately after ovulation up to Day 7 inhibited luteal angiogenesis as well as plasma progesterone (P) increase. Both treatments inhibited angiogenesis-and P synthesis-related genes, resulting in the inhibition of CL formation. Furthermore, it was demonstrated that blood supply and angiogenesis relate to "survival and growth" of follicles and CL, while the decrease in blood supply and vessel regression relate to "the death" of these organs.2. We examined in detail the phenomenon discovered by ourselves that "a local boold flow at periphery of mature CL increases prior to the onset of spontaneous luteolysis in the cow". As expected, it became evident that the endothelial cells of large blood vessels surrounding the CL have PGF receptor (FP-R), and NO synthease (NOS) is activated via binding of PGF2a to FP-R, thus endothelial cells release NO molecules locally, inducing vasodilation and the increase in blood flow. These were indicated by several evidence using immunohistochemistry and real-time PCR for relating genes in the CL tissue that obtained at 1 h after PG injection when the CL blood flow increased at maximum. Further evidence was obtaines by the in vivo experiments that direct injections of NO donor into the mid CL induced CL blood flow increase followed by luteolysis and the estrus, and that direct injections of NOS inhibitor blocked CL blood flow increase induced by PG injection and delayed the occurrence of luteolysis.

本系列研究从“血管生成和血管溶解”和“血管紧张”的窗口，从活体动物、黄体组织、细胞和基因的角度，采用多种实验模型，对奶牛的“黄体形成”和“黄体退化”进行了研究。本研究的主要成果如下：1.从排卵后立即到第7天，多次注射抗主要血管生成因子VEGF或bFGF的多克隆抗体直接进入黄体（CL）抑制黄体血管生成以及血浆孕酮（P）增加。两种处理均抑制血管生成和P合成相关基因，导致CL形成的抑制。此外，研究表明，血液供应和血管生成与卵泡和CL的“存活和生长”有关，而血液供应减少和血管退化与这些器官的“死亡”有关.我们详细研究了我们自己发现的现象，即“在奶牛自发性黄体溶解发生之前，成熟CL周围的局部血流增加”。正如所预期的，很明显CL周围大血管的内皮细胞具有PGF受体（FP-R），并且NO合成酶（NOS）通过PGF 2a与FP-R结合而被激活，因此内皮细胞局部释放NO分子，诱导血管舒张和血流量增加。这些都表明了几个证据，使用免疫组化和实时PCR相关的基因在CL组织中获得PG注射后1小时，当CL血流量增加到最大。体内实验进一步证实，直接注射NO供体可引起CL血流量增加，继而引起黄体溶解和发情，而直接注射NOS抑制剂可阻断PG注射引起的CL血流量增加，延缓黄体溶解的发生。

项目成果

Gene expression of glucose transporter (GLUT) 1, 3 and 4 in bovine follicle and corpus luteum

• DOI: 10.1677/joe.1.06210
• 发表时间: 2006-01-01
• 期刊: JOURNAL OF ENDOCRINOLOGY
• 影响因子: 4
• 作者: Nishimoto, H;Matsutani, R;Tetsuka, M
• 通讯作者: Tetsuka, M

Local mechanisms for luteolytis in the cow : novel roles of vasoactive substances in the luteolytic cascade within the corpus luteum.

牛黄体溶解的局部机制：血管活性物质在黄体内黄体溶解级联中的新作用。

• 发表时间: 2007
• 期刊: Animal Science Journal (In press)
• 作者: Kim;E.-H.et al.;Shirasuna K et al.
• 通讯作者: Shirasuna K et al.

Positive correlation in local release of luteal oxytocin with endothelin-1 and prostaglandin F2α during spontaneous luteolysis in the cow : A possible Intermediatory role for luteolytic cascade within the corpus luteum.

牛自发黄体溶解过程中黄体催产素与内皮素-1 和前列腺素 F2α 的局部释放呈正相关：黄体内黄体分解级联的可能中介作用。

• 发表时间: 2007
• 期刊: Biology of Reproduction (In press)
• 作者: Shirasuna K.;et al.
• 通讯作者: et al.

Relationship between metabolic hormones and ovulation of dominant follicle during the first follicular wave post-partum in high-producing dairy cows

• DOI: 10.1530/rep-06-0046
• 发表时间: 2007-01-01
• 期刊: REPRODUCTION
• 影响因子: 3.8
• 作者: Kawashima, Chiho;Fukihara, Saori;Miyamoto, Akio
• 通讯作者: Miyamoto, Akio

Changes in plasma metabolic hormones concentrations during the ovarian cycles of Japanese Black and Holstein cattle.

日本黑牛和荷斯坦牛卵巢周期期间血浆代谢激素浓度的变化。

• 发表时间: 2007
• 期刊: The journal of Reproduction and Development 53(2)
• 作者: Kawashima C.;et. al.
• 通讯作者: et. al.