Spontaneous lymphatic revascularization is a challenge and the establishment of new therapeutic strategies may improve life quality for patients suffering from lymphatic disorders. This study was designed to verify if VEGFC treatment improves lymphatic vascularization in a time‐dependent manner in mouse hindlimb ( HL ) after resection of the inguinal lymph node. Lymphatic vascular density (Vv) and length (Lv) were evaluated by stereology after immunohistochemistry. The control Group ( CG ) was not manipulated but received saline instead of VEGFC treatment. The surgery Group ( SG ) had the left inguinal lymph node resected but did not received VEGFC treatment. VEGFC Treated Group ( TG ) had the node resected and received VEGFC treatment. VEGFC and VEGFR 3 local expression were assessed by qPCR . There was an effect of time over Vv and Lv in the SG and significant difference between CG and SG in the regions studied (proximal, medium and distal regions) of the left HL ( LHL ). The Lv showed significant difference between CG and SG only in the medium region. The Vv and the Lv for TG were higher than the other groups. VEGFC and VEGFR 3 gene expression presented time effect in all regions of the LHL for SG and TG . Both VEGFC and VEGFR 3 gene expression presented significant difference between CG and SG , between SG and TG and between CG and TG . This study showed significant decrease in lymphatic vascularization in the left hindlimb of mice after surgical removal of the inguinal lymph node and adjacent lymphatic vessels. Exogenous VEGFC could recover lymphatic vascularization through stimulating neolymphangiogenesis.

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The canine corpus luteum (CL) is able to synthetise, activate and deactivate 17b-estradiol (E2) and also expresses nuclear estrogen receptors in a time-dependent manner during diestrus. Nevertheless, we are still missing a better comprehension of E2 functions in the canine CL, especially regarding the specific roles of estrogen receptor alpha (ERa) and ERb, encoded by ESR1 and 2, respectively. For that purpose, we analyzed transcriptomic data of canine non-pregnant CL collected on days 10, 20, 30, 40, 50 and 60 of diestrus and searched for differentially expressed genes (DEG) containing predicted transcription factor binding sites (TFBS) for ESR1 or ESR2. Based on biological functions of DEG presenting TFBS, expression of select transcripts and corresponding proteins was assessed. Additionally, luteal cells were collected across specific time points during diestrus and specificity of E2 responses was tested using ERa and/or ERb inhibitors. Bioinformatic analyses revealed 517 DEGs containing TFBS, from which 67 for both receptors. In general, abundance of predicted ESR1 targets was greater in the beginning, while abundance of ESR2 targets was greater in the end of diestrus. ESR1/ESR2 ratio shifted from an increasing to a decreasing pattern from day 30 to 40 post ovulation. Specific receptor inhibition suggested an ERa-mediated positive regulation of CL function at the beginning of diestrus and an ERb-mediated effect contributing to luteal regression. In conclusion, our data points toward a broad spectrum of action of E2 and its nuclear receptors, which can also act as transcription factors for other genes regulating canine CL function.