Cigarette smoke inhibits endometrial epithelial cell proliferation through a nitric oxide–mediated pathway

Khorram, Omid; Han, Guang; Magee, Thomas R.

doi:10.1016/j.fertnstert.2008.09.074

Cited by 36 publications

(27 citation statements)

References 47 publications

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“…cAMP-induced differentiation of hMSCs is blocked when exposed to cigarette smoke extract. Previous studies have shown that cigarette-smoke conditioned medium reduced proliferation of endometrial cells (Shiverick et al 1999; 2005; Khorram et al 2010) Although not characterized in this study, we speculate that smoking may also affect the physiology of stem cells in many organs and this may be a novel mechanism underlying pathogenesis of multiple diseases associated with smoking. Future studies will investigate the molecular mechanism by which smoking blocks stem cell infiltration and differentiation.…”

Section: Discussionmentioning

confidence: 51%

Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus

Zhou

Gan

Taylor

2011

Reproductive Toxicology

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Cigarette smoking leads to female infertility and a decreased incidence of endometriosis. Bone marrow derived stem cells are recruited to uterine endometrium and endometriosis. The effect of cigarette smoking on stem cell recruitment to any organ is uncharacterized. We hypothesized that bone marrow-derived mesenchymal stem cell recruitment to the uterus and differentiation would be diminished by cigarette smoke. We used human mesenchymal stem cells (hMSC) in vitro and a mouse model of cigarette smoke exposure. After myeloablation female C57BL/6J received bone marrow cells from males. Mice were exposed to room air or smoke from unfiltered cigarettes. Immunofluorescence and Y-FISH was performed on uterine sections. In vitro hMSCs were treated with 8-Br-cAMP to induce endometrial cell differentiation with or without cigarette smoke extract (CSE) and decidualization assessed morphologically and by prolactin expression. After 4 weeks the total number of Y-chromosome cells in the uterus was reduced by 68% in the smoke exposed mice. Both leukocytes and bone marrow derived endometrial cells were reduced by 60% and 73%, respectively. Differentiation of bone marrow derived cell to endometrial epithelial cells was reduced by 84%. hMSC treated with CSE failed to show cytological characteristics of decidualization. mRNA levels of the decidualization marker prolactin were decreased by 90% in CSE treated cells. Smoking inhibits both recruitment of bone marrow derived stem cells to uterus and stem cell differentiation. Inhibition of stem cells recruitment may be a general mechanism by which smoking leads to long term organ damage through inability to repair or regenerate multiple tissues.

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Section: Discussionmentioning

confidence: 51%

Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus

Zhou

Gan

Taylor

2011

Reproductive Toxicology

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“…HES cells have been used as a model of benign endometrial epithelium to study mucosal immunity [82], implantation [83, 84], decidualization [85] and endometriosis [86], and have served as ‘normal’ controls for novel chemotherapeutics [87, 88] and analysis of signaling pathways in the endometrium [89–93]. Similarly, the telomerase immortalized endometrial epithelial cell line, hTERT-EEC [59], was an exact genotypic match to MCF-7 breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination

Korch

Spillman

Jackson

et al. 2012

Gynecologic Oncology

216

184

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Objectives Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Methods Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability. Results Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Conclusions Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models.

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“…Based on our data we propose that excess eNOS expression in luminal epithelium of patients with RM and UI can create local oxidative stress which could impair implantation, similar to other inflammatory gynecologic conditions such as endometriosis (Dong et al 2001; Khorram and Lessey 2002; Ota et al 1998; Wu et al 2003), adenomyosis (Ota et al 1998), and adhesions (Saed and Diamond 2004). Exogenous factors such as cigarette smoking which has been associated with recurrent miscarriages (Cramer and Wise 2000) can also induce nitrosative stress through direct endometrial cell stimulation of eNOS expression, an effect which can be blocked by anti-oxidants such as ascorbic acid (Khorram et al 2010). Similarly ascorbate has recently been shown to activate eNOS activity by rapid modulation of its phosphorylation status (Ladurner et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Altered endometrial expression of endothelial nitric oxide synthase in women with unexplained recurrent miscarriage and infertility

Najafi

Novin

Ghazi

et al. 2012

Reproductive BioMedicine Online

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Background Endothelial nitric oxide synthase (eNOS) has diverse roles in the female reproductive system including a role in blastocyst implantation. Aberrant expression of eNOS could therefore be significant in the pathogenesis of disorders of implantation Materials and Methods eNOS protein and mRNA levels in the endometrium of women with recurrent miscarriages, unexplained infertility, and a control group was determined by compartmental quantitative immunohistochemistry and real time RT-PCR Results eNOS was immunolocalized to all layers of the endometrium and the vascular endothelium. eNOS protein expression was higher in glandular epithelium (P=0.004) and luminal epithelium (P=0.002) but not vascular endothelium and stroma (P=0.14) in women with recurrent miscarriage. Similarly, in women with unexplained infertility eNOS expression was significantly higher (P<0.03) in luminal epithelium but not in any other compartments compared with the control group. The levels of mRNA expression as determined by real time RT-PCR confirmed the protein data demonstrating higher eNOS mRNA expression In the endometrium of women with recurrent miscarriage and unexplained infertility compared with controls Conclusion Increased expression of eNOS in glandular and luminal epithelium of the endometrium in women with recurrent miscarriages and unexplained infertility suggests a detrimental effect of excess nitric oxide in endometrial receptivity and implantation

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Cigarette smoke inhibits endometrial epithelial cell proliferation through a nitric oxide–mediated pathway

Cited by 36 publications

References 47 publications

Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus

Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination

Altered endometrial expression of endothelial nitric oxide synthase in women with unexplained recurrent miscarriage and infertility

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