Expression of apoptosis-related genes in the endometrium of polycystic ovary syndrome patients during the window of implantation

Ling, Yan; Wang, Aiming; Chen, Lei; Shang, Wei; Li, Min; Zhao, Yong

doi:10.1016/j.gene.2012.06.037

Cited by 28 publications

(26 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, in organismal system pathway, osteoclast differentiation and chemokine signaling (hsa04380 and hsa04062 respectively); apoptosis (hsa04210) under cellular processes; PI3K-Akt signaling pathway (hsa04151) under environment information processing; and protein-processing in endoplasmic reticulum (hsa04141) under genetic information processing class were highly enriched. The results are in line with the findings where involvement of cancer(Dumesic & Lobo, 2013), osteoclast differentiation(Krishnan & Muthusami, 2017), apoptosis(Yan et al, 2012) and PI3k -Akt signaling pathway(Li et al, 2017) are found to be in close relationship with PCOS. The anti-PCOS effects of T. purpurea can be directly linked to these proteins through the protein targeting capability of its DPCs.To elucidate the cellular, molecular and biological level effects of T. purpurea, protein targets of this plant were subjected to gene ontology enrichment analysis.…”

supporting

confidence: 91%

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Choudhary

Singh

2019

Preprint

View full text Add to dashboard Cite

Tephrosia purpurea (T. purpurea), a plant belonging to Fabaceae (pea) family, is a well-known Ayurvedic herb and is commonly known as Sarapunkha in traditional Indian medicinal system. Described as "Sarwa wranvishapaka", i.e. having capability to heal all types of wounds, it is particularly recognized for its usage in splenomegaly. Towards exploring the comprehensive effects of T. purpurea against polycystic ovarian syndrome (PCOS), its phytochemicals were extensively reviewed and their network pharmacology evaluation is carried out in this study. The complex regulatory potential of its 76 phytochemicals (PCs) against PCOS are enquired by developing and analyzing high confidence tripartite networks of protein targets of each phytochemical at both pathway and disease association scales. We also developed a highconfidence human PPI sub-network specific to PCOS, explored its modular architecture and probed the drug-like phytochemicals (DPCs) having multi-module regulatory potential. The proteins belonging to endocrine system were identified as major targets of the PCs. The study reports 30 DPCs based on ADMET and drug-like properties. Multi-targeting and synergistic capacities of the 12 DPCs against 10 protein targets were identified and evaluated using molecular docking and interaction analyses. The study concludes by highlighting a couple of DPCs as potential sources of PCOS regulators.

show abstract

supporting

confidence: 91%

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Choudhary

Singh

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…A number of CAD genes in this study (e.g. PHACTR1 , LPL , PDGFD , IL6R , CNNM2 ) are found differentially expressed in PCOS women [79–83], suggesting possible links between perturbed embryogenesis and angiogenesis. In males, this can be demonstrated with a mutation in SLC22A5 that causes both cardiomyopathy and male infertility due to altered ability to break down lipids [84, 85].…”

Section: Resultsmentioning

confidence: 79%

Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

et al. 2017

View full text Add to dashboard Cite

Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

show abstract

“…Furthermore, evidence has also revealed that locally regulated apoptosis is important for the receptivity and decidualization of the endometrium (Castro et al, ; Makker & Goel, ; Toyofuku et al, ). Clinical data revealed that the endometrial cell apoptotic rate of patients with polycystic ovary syndrome was significantly lower than that of normal individuals, which facilitated a thickened, complicated, or atypical hyperplasia endometrium and eventually led to poor receptivity and defective implantation (Villavicencio et al, ; Yan et al, ). Meanwhile, another study showed that a large number of apoptotic cells were present in the endometrial tissues of normal pregnant uteri, but the number of apoptotic cells was decreased in the uterine endometria treated with molsidomine, thus decreasing the pregnancy rate (Wei, Yuan, Jin, Hu, & Liu, ).…”

Section: Discussionmentioning

confidence: 99%

Benzo(a)pyrene inhibits endometrial cell apoptosis in early pregnant mice via the WNT5A pathway

Liu

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Benzo(a)pyrene (BaP) is an endocrine‐disrupting pollutant present in various aspects of daily life, and studies have demonstrated that BaP exerts reproductive toxicity. We previously showed that BaP damages endometrial morphology and decreases the number of implantation sites in early pregnant mice, but the mechanisms underlying these effects remain unclear. The endometrial function is crucial for implantation, which is associated with endometrial cell apoptosis. In this study, we focused on the effect of BaP on endometrial cell apoptosis and the role of WNT signaling during this process. Pregnant mice were gavaged with corn oil (control group) or 0.2 mg·kg−1·day −1 BaP (treatment group) from Days 1 to 6 of pregnancy. BaP impaired endometrial function by decreasing the expression of HOXA10 and BMP2, two markers of receptivity and decidualization. WNT5A and β‐catenin were activated in the BaP group. BaP affected the expression of apoptosis‐related proteins and inhibited the apoptosis of endometrial stromal cells. In vitro, human endometrial stromal cells (HESCs) were treated with different concentrations of BaP (dimethyl sulfoxide (DMSO); 5, 10 µM). WNT5A and β‐catenin were also upregulated in the BaP treatment group. HESC apoptosis was restrained by BaP. Inhibiting WNT5A by SFRP5 partially restored the effect of BaP on apoptosis. In summary, these results suggested that BaP exposure during early pregnancy activates WNT5A/β‐catenin signaling pathway, which inhibits the endometrial cell apoptosis and potentially destroys endometrial function.

show abstract

Expression of apoptosis-related genes in the endometrium of polycystic ovary syndrome patients during the window of implantation

Cited by 28 publications

References 26 publications

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Deciphering the multi-scale mechanisms ofTephrosia purpureaagainst polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: studies from network-pharmacological perspective

Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

Benzo(a)pyrene inhibits endometrial cell apoptosis in early pregnant mice via the WNT5A pathway

Contact Info

Product

Resources

About