Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus Soane Nazare de Andrade, Ilheus, Brazil.
Hospital Veterinario, Departamento de Ciencias Agrarias e Ambientais, Universidade Estadual de Santa Cruz, Campus Soane Nazare de Andrade, Ilheus, Brazil.
Biol Reprod. 2021 Jul 2;105(1):217-231. doi: 10.1093/biolre/ioab061.
The Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone and luteinizing hormone release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N = 6) and late pregnancy (N = 6), in addition to uterus from non-pregnant cats in diestrus (N = 7), to evaluate protein and gene expression of kisspeptin (Kiss1), kisspeptin receptor (Kiss1r), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (Flk-1), placental growth factor (PLGF), interferon gamma (INFγ), migration inhibiting factor (MIF), tumor necrosis factor (TNFα), interleukins (IL6 and IL10) by immunohistochemistry and quantitative polymerase chain reaction. Pregnancy increased the uterine expression of Kiss1 and Kiss1r, especially at the late pregnancy, in addition to upregulating INFy, MIF, Vegf, Il10, and Tnf and downregulating Plgf. Higher placental expression of Kiss1r and Plgf mRNA occurred at the late pregnancy, while the expression of Kiss1, VEGF, Flk-1, INFy, TNFα, Il6, and IL10 was higher in the mid of pregnancy. A positive correlation between Kiss1 and Tnf was observed in the placenta, while Kiss1r had a negative correlation with Infγ, Il6, and Il10. The findings reveal that Kisspeptin/Kiss1r and angiogenic and immunological mediators at the maternal-fetal interface of pregnant cat have a gene correlation and are modulated by the gestational age. These data suggest possible functional links of Kisspeptin in placental angiogenesis and immunology.
Kisspeptin/Kiss1r 系统通过刺激促性腺激素释放激素和黄体生成素的释放，是生殖的关键调节剂，体外研究表明 Kisspeptin 可以调节血管生成和免疫功能，这些功能对生殖也是必不可少的。然而，目前还没有关于 Kisspeptin/Kiss1r 在国内猫的母胎界面的表达及其与血管生成和免疫介质的关系的研究。因此，我们的目的是评估 Kisspeptin/Kiss1r 及其在妊娠期间国内猫子宫和胎盘中的血管生成和免疫介质的时空表达谱。从中孕期（N=6）和晚孕期（N=6）的猫以及非妊娠发情期（N=7）的猫中收集子宫和胎盘样本，以评估 kisspeptin（Kiss1）、kisspeptin 受体（Kiss1r）、血管内皮生长因子（VEGF）、酪氨酸激酶受体（Flk-1）、胎盘生长因子（PLGF）、干扰素 γ（INFγ）、迁移抑制因子（MIF）、肿瘤坏死因子（TNFα）、白细胞介素（IL6 和 IL10）的蛋白和基因表达，通过免疫组织化学和定量聚合酶链反应。妊娠增加了子宫中 Kiss1 和 Kiss1r 的表达，尤其是在晚孕期，同时上调了 INFy、MIF、Vegf、Il10 和 Tnf，并下调了 Plgf。晚期妊娠时，胎盘 Kiss1r 和 Plgf mRNA 的表达较高，而中期妊娠时 Kiss1、VEGF、Flk-1、INFγ、TNFα、IL6 和 IL10 的表达较高。在胎盘组织中观察到 Kiss1 与 Tnf 之间存在正相关，而 Kiss1r 与 Infγ、Il6 和 Il10 之间存在负相关。这些发现表明，妊娠猫的母胎界面的 Kisspeptin/Kiss1r 和血管生成及免疫介质存在基因相关性，并受胎龄的调节。这些数据表明 Kisspeptin 在胎盘血管生成和免疫中的功能联系。
