Area of Electron Microscopy, Department of Animal Pathology, School of Agronomy and Veterinary, National University of Río Cuarto, Río Cuarto, Argentina.
National Scientific and Technical Research Council (CONICET), Argentina.
Reprod Fertil. 2022 Mar 8;3(1):57-66. doi: 10.1530/RAF-21-0092. eCollection 2022 Jan 1.
The aims of this study were to determine the changes in the capillary area density in relation to fetal development, to determine immunoexpression of angiogenic factors and to compare their mRNA expression throughout pig gestation. Samples were collected from the maternal-chorioallantoic interface at days 40, 77, 85 and 114 of pregnancy for immunohistochemistry analysis and the measurement of mRNA expression of and its receptors , respectively. Morphometric measurement of blood vessels was performed. We found a significant increase in capillary area density throughout gestation (< 0.05). On the maternal side, at day 77, we observed a significant increase in the number of vessels from small vascular areas ( < 0.05) and the vascular area was significantly higher on day 85 ( < 0.05). On the fetal side, the number of vessels and the vascular area increased between days 40 and 77 ( < 0.05) and between days 77 and 114 ( < 0.05), respectively. Immunohistochemical findings revealed intense VEGFA staining and a trend for increased expression towards the end of gestation ( < 0.05). We also demonstrated a high , and mRNA expression at day 77 ( < 0.05). In conclusion, our findings suggest that an active angiogenesis would be present even until late-middle gestation at day 77 of pregnancy with the predominance of angiogenic stimulation by VEGFA/KDR, FGF2/FGFR1 and a balance between ANGPT1 and ANGPT2/TEK.
Critical moments occur at different stages of placental formation in pigs, where the expression of angiogenic factors, that is, molecules that stimulate the formation of blood vessels must be adequate to promote their development. This exchange is necessary to cover the increasing nutritional demands of fetuses in continuous development. Determining the changes in the area of capillary density in relation to fetal development and the expression of angiogenic factors throughout pregnancy in pigs could contribute to understanding the causes of fetal loss. Placental samples were obtained at gestational days 40, 77, 85 and 114 ( = 7, 10, 7 and 5, respectively). We found that the capillary area density increases accompanying fetal growth with advancing gestation and an increase in capillary area density in late-middle gestation, around day 77, is due to the expansion in the number of small blood vessels on the maternal side. The present findings suggest that an intense angiogenesis would be present even until late-middle gestation at day 77 of pregnancy, with the predominance of angiogenic stimulation by specific molecules that promote this process.
本研究的目的是确定与胎儿发育相关的毛细血管面积密度的变化,确定血管生成因子的免疫表达,并比较它们在整个猪妊娠过程中的 mRNA 表达。在妊娠第 40、77、85 和 114 天,从母体-绒毛尿囊界面采集样本,用于免疫组织化学分析和 及其受体 的 mRNA 表达测量。对血管进行形态计量学测量。我们发现整个妊娠期间毛细血管面积密度显著增加(<0.05)。在母体侧,在第 77 天,我们观察到小血管区域的血管数量显著增加(<0.05),并且第 85 天血管面积显著升高(<0.05)。在胎儿侧,第 40 天至 77 天(<0.05)和第 77 天至 114 天(<0.05)之间,血管数量和血管面积分别增加。免疫组织化学结果显示 VEGFA 染色强烈,妊娠末期表达呈上升趋势(<0.05)。我们还证明了在第 77 天高的 、 和 mRNA 表达(<0.05)。总之,我们的研究结果表明,在妊娠第 77 天的中晚期妊娠中,血管生成可能仍然活跃,VEGFA/KDR、FGF2/FGFR1 对血管生成的刺激占主导地位,ANGPT1 和 ANGPT2/TEK 之间存在平衡。
在猪胎盘形成的不同阶段会出现关键时期,在这些时期,血管生成因子的表达,即刺激血管形成的分子,必须足够充分以促进其发育。这种交换对于满足不断发育的胎儿不断增加的营养需求是必要的。确定与胎儿发育相关的毛细血管密度变化以及在整个妊娠期间猪中血管生成因子的表达,可以帮助理解胎儿丢失的原因。在妊娠第 40、77、85 和 114 天( = 7、10、7 和 5)分别获得胎盘样本。我们发现,随着胎龄的增加,毛细血管面积密度伴随着胎儿的生长而增加,妊娠中期后期(约第 77 天)毛细血管面积密度的增加是由于母体侧小血管数量的增加所致。本研究结果表明,即使在妊娠第 77 天的中晚期妊娠中,强烈的血管生成也可能存在,由促进这一过程的特定分子引起的血管生成刺激占主导地位。