Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-University, Giessen, Germany.
Biol Reprod. 2023 Apr 11;108(4):645-658. doi: 10.1093/biolre/ioac214.
Glucocorticoids modulate the feto-maternal interface during the induction of parturition. In the dog, the prepartum rise of cortisol in the maternal circulation appears to be erratic, and information about its contribution to the prepartum luteolytic cascade is scarce. However, the local placental upregulation of glucocorticoid receptor (GR/NR3C1) at term led to the hypothesis that species-specific regulatory mechanisms might apply to the involvement of cortisol in canine parturition. Therefore, here, we assessed the canine uterine/utero-placental spatio-temporal expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1; reduces cortisone to cortisol), and -2 (HSD11B2; oxidizes cortisol to the inactive cortisone). Both enzymes were detectable throughout pregnancy. Their transcriptional levels were elevated following implantation, with a strong increase in HSD11B2 post-implantation (days 18-25 of pregnancy), and in HSD11B1 at mid-gestation (days 35-40) (P < 0.05). Interestingly, when compared pairwise, HSD11B2 transcripts were higher during post-implantation, whereas HSD11B1 dominated during mid-gestation and luteolysis (P < 0.05). A custom-made species-specific antibody generated against HSD11B2 confirmed its decreased expression at prepartum luteolysis. Moreover, in mid-pregnant dogs treated with aglepristone, HSD11B1 was significantly higher than -2 (P < 0.05). HSD11B2 (protein and transcript) was localized mostly in the syncytiotrophoblast, whereas HSD11B1 mRNA was mainly localized in cytotrophoblast cells. Finally, in a functional approach using placental microsomes, a reduced conversion capacity to deactivate cortisol into cortisone was observed during prepartum luteolysis, fitting well with the diminished HSD11B2 levels. In particular, the latter findings support the presence of local increased cortisol availability at term in the dog, contrasting with an enhanced inactivation of cortisol during early pregnancy.
糖皮质激素在分娩诱导过程中调节胎-母界面。在犬中，母循环中皮质醇的产前升高似乎不稳定，并且关于其对产前黄体溶解级联的贡献的信息很少。然而，在足月时胎盘局部上调糖皮质激素受体（GR/NR3C1）导致了这样的假设，即特定于物种的调节机制可能适用于皮质醇在犬分娩中的参与。因此，在这里，我们评估了犬子宫/子宫胎盘的时空表达羟类固醇 11-β 脱氢酶 1（HSD11B1；将皮质酮还原为皮质醇）和-2（HSD11B2；将皮质醇氧化为无活性的皮质酮）。这两种酶在整个怀孕期间都可检测到。它们的转录水平在植入后升高，植入后 HSD11B2 强烈增加（妊娠第 18-25 天），妊娠中期 HSD11B1 增加（妊娠第 35-40 天）（P<0.05）。有趣的是，当两两比较时，HSD11B2 转录本在植入后较高，而 HSD11B1 在妊娠中期和黄体溶解时占主导地位（P<0.05）。针对 HSD11B2 生成的定制的种特异性抗体证实了其在产前黄体溶解时的表达降低。此外，在接受阿格利司酮治疗的妊娠中期犬中，HSD11B1 明显高于 -2（P<0.05）。HSD11B2（蛋白质和转录本）主要定位于合体滋养层，而 HSD11B1 mRNA 主要定位于细胞滋养层细胞。最后，在使用胎盘微粒体的功能方法中，在产前黄体溶解期间观察到将皮质醇失活为皮质酮的转化能力降低，这与 HSD11B2 水平降低非常吻合。特别是，后一种发现支持在犬中足月时胎盘局部皮质醇可用性增加的存在，与妊娠早期皮质醇失活增强形成对比。
