scholarly journals Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester

2020 ◽  
Author(s):  
AMIN NAMDARI ◽  
FARIDEH MOHAMMADIAN ◽  
Fatemeh KHAJEH ◽  
SOUDABEH KAVOUSIPOUR ◽  
behnoosh miladpour
Keyword(s):  
Protective Effect ◽  
Caffeic Acid ◽  
Stromal Cells ◽  
Reproductive System ◽  
Quantitative Polymerase Chain Reaction ◽  
Protective Effects ◽  
Uterine Receptivity ◽  
Endometrial Stromal Cells ◽  
Genes Expression ◽  
Endometrium Receptivity

Abstract Background nicotine adversely affects the female reproductive system and changes the methylation pattern of some genes in the placenta. In contrast, caffeic acid phenylethyl ester) CAPE (, as a potent antioxidant, has protective effects against the harmful effects of oxygen free radical molecules, methotrexate, and pesticides on the reproductive system. To find the effect of nicotine on the endometrium, we investigated three markers of endometrium receptivity including fibroblast growth factor 2, vascular endothelial growth factors A, and C-X-C motif chemokine ligand 12 and also changes in methylation levels of CXCL-12 gene promoter. In addition, we evaluated the protective effect of CAPE against nicotine. Methods the appropriate treatment dose was selected based on the literature, the endometrial stromal cells were divided into 4 groups, including control, treated with nicotine, CAPE, and nicotine followed by CAPE. Finally, the quantitative polymerase chain reaction and Methylation-Specific PCR were carried out. Results The results showed that treatment of endometrial stromal cells with nicotine (10− 6 µM) for 24 h significantly reduced expression of CXCL-12, FGF, and VEGFA genes. However, a decrease in CXCL-12 expression was not associated with increased methylation levels in the studied promoter region. In contrast, endometrial stromal cells treated with CAPE (4 µg/ml) for 24 h adverse significantly nicotine-induced reduction of CXCL-12, FGF, and VEGFA genes expression. Conclusion Exposure to nicotine has negative effects on uterine receptivity, implantation, and fertility, via reducing the expression of VEGFA, CXCL-12, and FGF2 genes. In contrast, CAPE has a protective effects and improves these genes expression.

scholarly journals Kefir as a Prevention of Arsenic-mediated Toxicity in Uterine Female Rats

2021 ◽  
Vol 4 (4) ◽  
Author(s):  
Sabatina Windyaningrum ◽  
◽  
Tri Yudani Mardining Raras ◽  
Bambang Rahardjo ◽  
Rose Khasana Dewi
Keyword(s):  
Protective Effect ◽  
Arsenic Trioxide ◽  
Stromal Cells ◽  
Wistar Rats ◽  
Endometrial Thickness ◽  
Normal Diet ◽  
Female Rats ◽  
Tissue Preparation ◽  
Endometrial Stromal Cells ◽  
Female Wistar Rats

Background: kefir is a fermented milk product that demonstrates numerous health benefits including antioxidant and immunomodulatory. Aim: to study the protective effect kefir on the expression of estrogen receptor alpha (ERα) in endometrial stromal cells and endometrial thickness on female rats that were exposed to arsenic. Methods: twenty-five female Wistar rats (Rattus norvegicus) were divided into five groups (CRL, As, T1, T2, T3). Control group (given a normal diet), As group (given the normal diet and exposed to arsenic trioxide 2 mg/kgBW/day). The T1; T2; T3 were exposed to arsenic trioxide 2 mg/kgBW/day and treated with different doses of kefir (1.25; 2.5; and 5 mL/kgBW/day, respectively) for 35 days. The rats of group As treated with arsenic trioxide only and group CRL served as control with normal feed in water. Cytological samples were taken after 35 days of treatment and examined every day to see the rat oestrus phase, and the proestrus phase of the oestrous cycle was chosen for termination. Uterine tissue fixed in 10% neutral buffered formalin for tissue preparation. ERα expression in endometrial stromal cells was analized using immunohistochemistry method, endometrial thickness was observed using histopathological methods. Results: significant reduction of ERα expression in endometrial stromal cells and endometrial thickness in female rats exposed to arsenic were observed in groups on treated rats (p ≤ 0.000; 0.009, respectively). Conclusion: the administration of kefir in female Wistar rats exposed to arsenic had shown significantly differences on ERα expressions and endometrial thickness. The smallest dose of kefir (1.25 mL/kgBW/day) could increase ERα expression and endometrial thickness in female Wistar rats with arsenic exposure. Therefore kefir has protective effect related to female reproductive system.

scholarly journals Hoxa-10 and Cyclin D3 Overexpression in the Decidual Reaction in a Superovulation Protocol in Young Adult C57BL/6J Mice

2016 ◽  
Vol 54 (2) ◽  
pp. 328-335 ◽  
Author(s):  
T. Garcia Robles ◽  
R. A. García Fernández ◽  
P. García-Palencia ◽  
M. D. Arrabal ◽  
B. Sánchez Maldonado ◽  
...  
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cyclin D3 ◽  
Proliferation Index ◽  
Control Group ◽  
Ki 67 ◽  
Endometrial Stromal Cells ◽  
Decidual Cells ◽  
Decidual Reaction

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction.

scholarly journals Quantitative Analysis of Glucose Transporter mRNAs in Endometrial Stromal Cells Reveals Critical Role of GLUT1 in Uterine Receptivity

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 2123-2128 ◽  
Author(s):  
Antonina I. Frolova ◽  
Kelle H. Moley
Keyword(s):  
Stromal Cells ◽  
Glucose Transporter ◽  
Critical Role ◽  
Early Embryo ◽  
Absolute Amount ◽  
Uterine Receptivity ◽  
Endometrial Stromal Cells ◽  
Decidual Cells ◽  
Before And After ◽  
Glut1 Mrna

Recurrent miscarriages affect about 1–2% of couples trying to conceive; however, mechanisms leading to this complication are largely unknown. Most studies focus on the early embryo, but proper development and implantation of the blastocyst are also dependent on optimal endometrial progression into a receptive state. One of the key steps in the uterine preparation for embryo receptivity, known as decidualization, is the differentiation of endometrial stromal cells (ESCs) into decidual cells. During this transition, the ESCs undergo a drastic change in glucose metabolism. The efficiency of glucose uptake is determined by a family of facilitative glucose transporters (GLUTs), and many have been identified in the stroma. The primary focus of this work was to quantify the absolute amount of GLUT mRNAs in this cell type before and after decidualization. We used primary ESCs isolated from murine and human uteri. We developed and validated cDNA-based calibration curves for each GLUT and used these primers to arrive at absolute mRNA copy numbers. Here, we report all the GLUT mRNAs that are present in the ESCs and their abundance under both conditions, control and decidualized. GLUT1 mRNA is the most abundant and critical transporter in ESCs of both species, because knocking down this GLUT with sort hairpin RNA leads to dramatically reduced decidualization. These findings suggest that GLUT1 mRNA expression is essential for decidualization and we are the first to determine a possible mechanism to explain how maternal conditions of abnormal glucose utilization may impair implantation at the level of the ESCs.

scholarly journals Functional Differentiation of Uterine Stromal Cells Involves Cross-Regulation between Bone Morphogenetic Protein 2 and Krüppel-Like Factor (KLF) Family Members KLF9 and KLF13

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3396-3406 ◽  
Author(s):  
John Mark P. Pabona ◽  
Zhaoyang Zeng ◽  
Frank A. Simmen ◽  
Rosalia C. M. Simmen
Keyword(s):  
Bone Morphogenetic Protein ◽  
Stromal Cells ◽  
Functional Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Mrna Levels ◽  
Uterine Receptivity ◽  
Endometrial Stromal Cells ◽  
Interacting Protein ◽  
Morphogenetic Protein ◽  
Implantation Success

The inability of the uterine epithelium to enter a state of receptivity for the embryo to implant is a significant underlying cause of early pregnancy loss. We previously showed that mice null for the progesterone receptor (PGR)-interacting protein Krüppel-like factor (KLF) 9 are subfertile and exhibit reduced uterine progesterone sensitivity. KLF9 expression is high in predecidual stroma, undetectable in decidua, and enhanced in uteri of mice with conditional ablation of bone morphogenetic protein 2 (BMP2). Given the individual importance of KLF9 and BMP2 for implantation success, we hypothesized that the establishment of uterine receptivity involves KLF9 and BMP2 functional cross-regulation. To address this, we used early pregnant wild-type and Klf9 null mice and KLF9 small interfering RNA-transfected human endometrial stromal cells (HESCs) induced to differentiate under standard conditions. Loss of KLF9 in mice and HESCs enhanced BMP2 expression, whereas recombinant BMP2 treatment of HESCs attenuated KLF9 mRNA levels. IGFBP1 and KLF9-related KLF13 expression were positively associated with BMP2 and inversely associated with KLF9. Prolonged, but not short-term, knockdown of KLF9 in HESCs reduced IGFBP1 expression. Mouse uterine Igfbp1 expression was similarly reduced with Klf9 ablation. PGR-A and PGR-B expression were positively associated with KLF9 in predecidual HESCs but not decidualizing HESCs. KLF13 knockdown attenuated BMP2 and PGR-B and abrogated BMP2-mediated inhibition of KLF9 expression. Results support cross-regulation among BMP2, KLF9, and KLF13 to maintain progesterone sensitivity in stromal cells undergoing differentiation and suggest that loss of this regulatory network compromises establishment of uterine receptivity and implantation success.

scholarly journals The autophagy protein, FIP200 (RB1CC1) mediates progesterone responses governing uterine receptivity and decidualization†

2020 ◽  
Vol 102 (4) ◽  
pp. 843-851 ◽  
Author(s):  
Arin K Oestreich ◽  
Sangappa B Chadchan ◽  
Alexandra Medvedeva ◽  
John P Lydon ◽  
Emily S Jungheim ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Conditional Knockout ◽  
Trophoblast Invasion ◽  
Uterine Receptivity ◽  
Human Escs ◽  
Embryo Survival ◽  
Endometrial Stromal Cells ◽  
Cellular Changes ◽  
Decidual Cells

Abstract Successful establishment of pregnancy depends on steroid hormone-driven cellular changes in the uterus during the peri-implantation period. To become receptive to embryo implantation, uterine endometrial stromal cells (ESCs) must transdifferentiate into decidual cells that secrete factors necessary for embryo survival and trophoblast invasion. Autophagy is a key homeostatic process vital for cellular homeostasis. Although the uterus undergoes major cellular changes during early pregnancy, the precise role of autophagy in uterine function is unknown. Here, we report that conditional knockout of the autophagy protein FIP200 in the reproductive tract of female mice results in reduced fecundity due to an implantation defect. In the absence of FIP200, aberrant progesterone signaling results in sustained uterine epithelial proliferation and failure of stromal cells to decidualize. Additionally, loss of FIP200 impairs decidualization of human ESCs. We conclude that the autophagy protein FIP200 plays a crucial role in uterine receptivity, decidualization, and fertility. These data establish autophagy as a major cellular pathway required for uterine receptivity and decidualization in both mice and human ESCs.

scholarly journals Kefir as a Prevention of Arsenic-mediated Toxicity in Uterine Female Rats

2021 ◽  
Author(s):  
Sabatina Windyaningrum ◽  
Tri Yudani Mardining Raras ◽  
Bambang Rahardjo ◽  
Rose Khasana Dewi
Keyword(s):  
Protective Effect ◽  
Arsenic Trioxide ◽  
Stromal Cells ◽  
Wistar Rats ◽  
Endometrial Thickness ◽  
Normal Diet ◽  
Female Rats ◽  
Tissue Preparation ◽  
Endometrial Stromal Cells ◽  
Female Wistar Rats

Background: kefir is a fermented milk product that demonstrates numerous health benefits including antioxidant and immunomodulatory. Aim: to study the protective effect kefir on the expression of estrogen receptor alpha (ERα) in endometrial stromal cells and endometrial thickness on female rats that were exposed to arsenic. Methods: twenty-five female Wistar rats (Rattus norvegicus) were divided into five groups (CRL, As, T1, T2, T3). Control group (given a normal diet), As group (given the normal diet and exposed to arsenic trioxide 2 mg/kgBW/day). The T1; T2; T3 were exposed to arsenic trioxide 2 mg/kgBW/day and treated with different doses of kefir (1.25; 2.5; and 5 mL/kgBW/day, respectively) for 35 days. The rats of group As treated with arsenic trioxide only and group CRL served as control with normal feed in water. Cytological samples were taken after 35 days of treatment and examined every day to see the rat oestrus phase, and the proestrus phase of the oestrous cycle was chosen for termination. Uterine tissue fixed in 10% neutral buffered formalin for tissue preparation. ERα expression in endometrial stromal cells was analized using immunohistochemistry method, endometrial thickness was observed using histopathological methods. Results: significant reduction of ERα expression in endometrial stromal cells and endometrial thickness in female rats exposed to arsenic were observed in groups on treated rats (p ≤ 0.000; 0.009, respectively). Conclusion: the administration of kefir in female Wistar rats exposed to arsenic had shown significantly differences on ERα expressions and endometrial thickness. The smallest dose of kefir (1.25 mL/kgBW/day) could increase ERα expression and endometrial thickness in female Wistar rats with arsenic exposure. Therefore kefir has protective effect related to female reproductive system.

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