Department of Animal Production, School of Agriculture, The Universityof Jordan, Amman, Jordan.
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, USA.
Biol Reprod. 2020 Mar 13;102(3):680-692. doi: 10.1093/biolre/ioz211.
Follicular progression during peripuberty is affected by diet. Vascular endothelial growth factor A (VEGFA) induces follicle progression in many species; however, there are limited studies to determine if diet may alter the effects of angiogenic VEGFA165-stimulated follicle progression or antiangiogenic VEGFA165b follicle arrest. We hypothesized that diet affects the magnitude of angiogenic and antiangiogenic VEGFA isoform actions on follicular development through diverse signal transduction pathways. To test this hypothesis, beef heifers in our first trial received Stair-Step (restricted and refeeding) or control diets from 8 to 13 months of age. Ovaries were collected to determine follicle stages, measure vascular gene expression and conduct ovarian cortical cultures. Ovarian cortical cultures were treated with phosphate-buffered saline (control), 50 ng/ml VEGFA165, VEGFA165b, or VEGFA165 + VEGFA165b. The Stair-Step heifers had more primordial follicles (P < 0.0001), greater messenger RNA abundance of vascular markers VE-cadherin (P < 0.0001) and NRP-1 (P < 0.0051) than controls at 13 months of age prior to culture. After culture, VEGFA isoforms had similar effects, independent of diet, where VEGFA165 stimulated and VEGFA165b inhibited VEGFA165-stimulated follicle progression from early primary to antral follicle stages. In vitro cultures were treated with VEGFA isoforms and signal transduction array plates were evaluated. VEGFA165 stimulated expression of genes related to cell cycle, cell proliferation, and growth while VEGFA165b inhibited expression of those genes. Thus, VEGFA isoforms can act independently of diet to alter follicle progression or arrest. Furthermore, follicle progression can be stimulated by VEGFA165 and inhibited by VEGFA165b through diverse signal transduction pathways.
青春期前后卵泡的发育受到饮食的影响。血管内皮生长因子 A（VEGFA）在许多物种中诱导卵泡发育；然而，目前还没有研究来确定饮食是否会改变血管生成的 VEGFA165 刺激的卵泡发育或抗血管生成的 VEGFA165b 卵泡阻滞的作用。我们假设饮食通过不同的信号转导途径影响血管生成和抗血管生成 VEGFA 同工型对卵泡发育的作用程度。为了验证这一假设，我们的第一项试验中的肉牛小母牛从 8 到 13 月龄接受阶梯式（限制和再喂养）或对照饮食。采集卵巢以确定卵泡阶段，测量血管基因表达并进行卵巢皮质培养。用磷酸盐缓冲盐水（对照）、50ng/ml VEGFA165、VEGFA165b 或 VEGFA165+VEGFA165b 处理卵巢皮质培养物。阶梯式小母牛在 13 月龄接受培养前比对照具有更多的原始卵泡（P<0.0001），血管标记物 VE-钙粘蛋白（P<0.0001）和 NRP-1（P<0.0051）的信使 RNA 丰度更高。培养后，VEGFA 同工型具有相似的作用，与饮食无关，VEGFA165 刺激，VEGFA165b 抑制从早期初级到腔前卵泡阶段的 VEGFA165 刺激的卵泡发育。用 VEGFA 同工型处理体外培养物，并评估信号转导阵列板。VEGFA165 刺激与细胞周期、细胞增殖和生长相关的基因表达，而 VEGFA165b 抑制这些基因的表达。因此，VEGFA 同工型可以独立于饮食改变卵泡发育或阻滞。此外，VEGFA165 可刺激卵泡发育，VEGFA165b 通过不同的信号转导途径抑制卵泡发育。
