A Histopathological Evaluation of Ovarian Hyperstimulation Syndrome on Reproductive and Vital Organs and the Role of the VEGF-PKA Pathway in a Mouse Model

2021 ◽  
pp. 1-20
Author(s):  
Seda Karabulut ◽  
Oya Korkmaz ◽  
Ceren Erdem Altun ◽  
Ilknur Keskin

Ovarian hyperstimulation syndrome (OHSS) is one of the most common and iatrogenic complications of in vitro fertilization therapy, which is an exaggerated response to excess hormones resulting in the development of a large number of maturing follicles. Although the complications of and reasons for the condition are well known, the overall histopathological effects on systemic organs and the extent of the damage have not been fully elucidated. Besides, the mechanism that underlies the situation is not very well known. The aim of the present work was to analyse the histopathological effects of OHSS on reproductive (uterus and ovary) and vital organs (liver and kidney) and the possible role of the VEGF-PKA pathway in triggering the condition. Balb/c mice were used to establish an OHSS model. The OHSS group were injected with overdose PMSG while the normal responder group were injected with an optimal dose. Histopathological evaluation was utilised in the liver, kidney, ovary, and uterus stained with hematoxylin and eosin, Masson’s trichrome, and periodic acid-Schiff stain. The expression profiles of VEGF (vascular endothelial growth factor), PKA (protein kinase A), and p-PKA (an activated form of PKA) were detected with immunohistochemistry and Western blotting. OHSS was demonstrated to have a negative histopathological effect on all of the organs analysed. These effects were associated with an overall increase in the expression levels of VEGF, PKA, and p-PKA. OHSS has a serious histopathological negative effect on the systemic and reproductive organs and is proven to affect overall health, and thus should be considered a dangerous complication during ART techniques. The activation of the VEGF-PKA pathway, which is indicated by the expression levels of VEGF, PKA, and p-PKA, is demonstrated to accompany this complication, which should be further elucidated to understand the mechanisms underlying the condition.

2015 ◽  
Vol 2015 ◽  
pp. 1-14
Author(s):  
Hao Zhou ◽  
Shun Chen ◽  
Yulin Qi ◽  
Qin Zhou ◽  
Mingshu Wang ◽  
...  

Interferonγreceptor 1 (IFNGR1) and IFNGR2 are two cell membrane molecules belonging to class II cytokines, which play important roles in the IFN-mediated antiviral signaling pathway. Here, goose IFNGR1 and IFNGR2 were cloned and identified for the first time. Tissue distribution analysis revealed that relatively high levels of goose IFNγmRNA transcripts were detected in immune tissues, including the harderian gland, cecal tonsil, cecum, and thymus. Relatively high expression levels of both IFNGR1 and IFNGR2 were detected in the cecal tonsil, which implicated an important role of IFNγin the secondary immune system of geese. No specific correlation between IFNγ, IFNGR1, and IFNGR2 expression levels was observed in the same tissues of healthy geese. IFNγand its cognate receptors showed different expression profiles, although they appeared to maintain a relatively balanced state. Furthermore, the agonist R848 led to the upregulation of goose IFNγbut did not affect the expression of goose IFNGR1 or IFNGR2. In summary, trends in expression of goose IFNγand its cognate receptors showed tissue specificity, as well as an age-related dependency. These findings may help us to better understand the age-related susceptibility to pathogens in birds.


1991 ◽  
Vol 56 (6) ◽  
pp. 1077-1083 ◽  
Author(s):  
Juan Balasch ◽  
Vicente Arroyo ◽  
Francisco Carmona ◽  
José Llach ◽  
Wladimiro Jiménez ◽  
...  

2016 ◽  
Vol 428 ◽  
pp. 161-169 ◽  
Author(s):  
Nozomi Takahashi ◽  
Miyuki Harada ◽  
Yasushi Hirota ◽  
Lin Zhao ◽  
Osamu Yoshino ◽  
...  

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.


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