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With the increase of the world population, the worries and concerns for food supply increase too. Wheat, as one of the most important agricultural products, which is widely consumed all over the world, has a very important role in people's nutrition, particularly among Iranians, the diet of whom is highly dependent on bread. Product forecasting is critical for any country so that decisions about storage, import or export, etc. can be planned. In this paper, several univariate time series models and the Artificial Neural Network (ANN) model are used to forecast wheat production in Iran. Annual wheat production, total annual precipitation, total applied fertilizer, population, and wheat cultivated area data were used in the period between 1961-1962 to 2018-2019. With the minimum values of 1.45894, 1.00329, 1.0448, and 1.09742 obtained for RMSE, AIC, HQC, and SIBC criteria, respectively, Autoregressive Integrated Moving Average (ARIMA) (1,1,1) was selected as the best univariate model. In testing the ANN models, total annual precipitation, total applied fertilizer, population, and wheat cultivated, area as input variables, and wheat production, as output variable, were used. Among several NN models, the Multilayer Perceptron Neural Network (MLP-NN) model with five hidden layers had the lowest MSE= 0.153 and was chosen in this study. Comparison between the ANN model and the ARIMA (1,1,1) model showed that RMSE= 0.391, MSE= 0.153, and MAPE= 0.4231 in the ANN model were much lower than that of the ARIMA (1,1,1) model. The results showed the power of ANN models to predict wheat production using efficient parameters, as compared to the ARIMA model. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D in combination with its receptors can be involved in implantation by regulating gene expression, endometrium immune response and stimulation of endometrium decidualization. So, it seems that the amount of vitamin D in follicular fluids (FF) may has an association with ART success. Materials and Methods: In a prospective study, 80 infertile female candidates for IVFV ICSI were enrolled. Blood samples (on the day of human chorionic gonadotropin) and follicular fluids were taken, and then levels of serum estradiol and follicular fluids 25-OH vitamin D were measured. Also clinical characteristics of patients (duration of infertility, causes of infertility, and menstrual status), number and quality of oocytes, number of fertilized oocytes, estradiol levels, and clinical pregnancy were evaluated. Results: Concentration of FF 25-OH vitamin D in pregnant women was significantly higher than nonpregnant women (p=0.007) but there were no significant differences in age, body mass index (BMI), duration of infertility, menstrual status, number of oocytes, oocytes quality, number of fertilized oocytes and serum estradiol levels between the two groups (p>0.05). Statistically positive correlation was found between 25-OH vitamin D levels with patient age and implantation rate (r=0.264, p=0.018 and r=0.301, p=0.007 respectively). Conclusion: The obtained results suggest that vitamin D without affecting the number and quality of oocytes can independently improve implantation rate and IVF outcome. [ABSTRACT FROM AUTHOR]

Introduction: Paraoxonasel (PON1) is a glycoprotein associated with high density lipoprotein and has antioxidant activity. The impact of PON1 in various stages of spermatogenesis has also been suggested. Materials and Methods: Q192R variants of PONl were determined in 150 fertile and 150 infertile men using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Plasma arylesterase and paraoxonase activities were detected by spectrophotometry and malondialdehyde (MDA) level was measured using thiobarbituric acid. Results: Our results showed no significant difference in the distribution of PONl genotypes and alleles between fertile and infertile groups. However morphology and motility of sperm were associated with various genotypes of PONl. The number of fertile males with the BB phenotype (high activity) was significantly higher than that of infertile males, whereas the number of individuals with the AB phenotype (moderate activity) was statistically higher in infertile men compared with the fertile group. Additionally, MDA and arylesterase activity levels were significantly higher in infertile subjects compared with fertile men. Conclusion: We speculate that the low activity of PON 1 can be a risk factor for male infertility probably due to a decrease in antioxidant activity of PON 1 and increase in lipid peroxidation. [ABSTRACT FROM AUTHOR]

This study conducts an in-depth review of the correlation between testis tissue changes and circulating microRNAs (miRNA) in diabetes-induced male reproductive complications, drawing upon both animal and clinical studies. The original articles published in English that specifically investigate miRNAs linked to male infertility in humans or animals with either type I or ΙΙ diabetes mellitus were included. The relevant articles were gathered from the PubMed, Google Scholar, Cochrane Library, and ScienceDirect databases. The quality of study was assessed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Prevalence Studies. We collected an overall number of 1989 citations relating to our research subject. Following the elimination of articles based on the criteria, a total of 20 papers were included in the study. Aberrant expression profiles of 25 miRNAs were identified in diabetes associated with male reproductive issues, with 15 miRNAs exhibiting increased expression and 10 miRNAs showing decreased expression. Among the chosen publications, eighteen were identified as low-risk and two were classed as moderate quality. The dysregulated miRNAs were linked to testicular injury, disrupted steroid production, decreased sperm development and quality, and erectile dysfunction. The results demonstrate that the miRNA-mRNA network is linked to the pathological progression of diabetic testicular damage or erectile dysfunction. From a therapeutic perspective, the identification of circulating miRNAs could be beneficial in the timely identification and prevention of diabetes problems, such as diabetes-induced male infertility. Among all signaling pathways influenced by modified miRNAs, the Bax-caspase-3, MAPK, PI3K-Akt, and eNOS-cGMP-PKC were the main deregulated pathways., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent to publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Polycystic ovary syndrome (PCOS) is a primary endocrinological disorder in women of reproductive age that is characterized by androgen excess and ovulatory irregularities. This syndrome is associated with adipose tissue dysfunction, an elevated risk of insulin resistance, hyperinsulinemia, obesity, and type 2 diabetes. Adipocyte dysfunction affects the secretion of adipokines and pro-inflammatory cytokines. Nevertheless, adipose tissue is not an exclusive source of adipokines as it can also be produced locally by reproductive tissues. Although adipokines have been recognized in the development of PCOS, the role of oncostatin M (OSM), a multifaceted adipokine, remains unclear. Current evidence suggests that this cytokine is associated with key aspects of the syndrome, including obesity, insulin resistance, hyperandrogenism, and inflammation. However, the data are often contradictory, likely due to variations in study designs, methodologies, and species differences. By investigating the link between OSM and PCOS-associated issues, this review identified the potential role of this adipokine in PCOS pathogenesis. This underscores the need for further research to clarify its predominant effects and assess its relevance as a therapeutic target.

The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer., (© 2024. The Author(s).)

It is essential to focus on the variables that can empower mothers of single-parent students. The present study aimed to investigate the effects of self-healing training on perfectionism and frustration tolerance in mothers of single-parent students. The statistical population included all divorced mothers of elementary school students within the 2020-21 academic year. Sampling was performed in two stages, the first of which was multistage cluster sampling, whereas the second stage was purposive sampling based on inclusion and exclusion criteria. The study sample (n = 40) was divided into two groups of 20 (control and experimental). This quasi-experimental research adopted a pretest-posttest control group design with follow-up. The experimental group was trained in the self-healing protocol for fourteen weekly 90-minute sessions. The repeated measures ANOVA in SPSS-26 was then used for data analysis. The mean ± SD of perfectionism in the self-healing and control groups in the posttest was 67.75 ± 11.84 and 106.05 ± 22.01. Moreover, in the posttest stage, the mean ± SD of frustration tolerance in the intervention and control groups was 78.60 ± 7.93 and 99.45 ± 9.36, respectively. According to findings, self-healing training significantly affected the components of perfectionism including personal standards, concern over mistakes, and parental criticism. It also had significant effects on the components of frustration tolerance including discomfort intolerance, emotional intolerance, and achievement made by single mothers of students. The results were stable over time. However, self-healing training had no significant effects on perfectionism entitlement and subscales of frustration tolerance including discipline and organization, doubt about actions, and parental expectations.

Aim: This study examined the levels of VitD, VitD binding protein (DBP), and free VitD in leiomyomas patients and their association with the quantity, dimensions, and site of fibroid growths. Additionally, we evaluated the potentiality of employing these factors as a biomarker tool for the diagnosis and assessment of uterine fibroid progression., Methods: This study involved the participation of 55 women with leiomyomas and 50 healthy women. We utilized commercial ELISA kits to measure the levels of total VitD and DBP in their serum. Additionally, we calculated the levels of free VitD and the ratio of VitD to DBP. Moreover, we determined the number, size, and location of the leiomyomas in the patients., Results: There were no significant differences in the levels of total VitD between the groups. However, patients had significantly lower levels of free VitD and higher levels of DBP compared to the control group. The size of the largest leiomyomas showed a negative relationship with free VitD and a positive relationship with DBP. Receiver operating characteristic analyses, showed that the cut-off value for free VitD was 4.47 pg/mL, with a sensitivity of 75.6% and a specificity of 74.4%. The cut-off value for DBP was 256.2 μg/mL, with a sensitivity of 86% and a specificity of 70.3%., Conclusions: Free VitD and DBP potentially contribute to the development of leiomyomas and are linked to the size of these tumors. The measurement of serum levels of these factors could serve as additional biomarkers for the diagnosis of leiomyomas., (© 2024 Japan Society of Obstetrics and Gynecology.)

A novel edible coating containing basil seed gum (0.1, 0.3, and 0.5%), Salvia macrosiphon seed gum (0.25, 0.5, and 0.75%), and Arabic gum (10%) at normal pH and pH 5/6 has been used as a postharvest treatment to maintain tomato quality and safety. In this study, the physicochemical properties of tomatoes were investigated during 35 days of storage at 4°C. During storage, coated fruit showed increases in vitamin C retention, reduced weight loss, color changes, and accelerated softening. However, treatment of tomatoes with gum significantly delayed onset of parameters related to loss of postharvest quality, and storability was extended. All the coated samples had increased vitamin C retention compared with controls, with highest contents observed for tomatoes coated in basil seed gum 0.1% and Arabic gum at pH 5.6. In conclusion, basil seed gum 0.1%, S. macrosiphon seed gum 0.25 and 0.5%, and Arabic gum at normal pH were the best treatments for maintaining postharvest quality of tomatoes., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2021 by The Korean Society of Food Science and Nutrition.)

In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Endometrial exosomes carry bioactive agents to uterine epithelial cells and trophectoderm to promote implantation. On the other hand, intrauterine administration of human chorionic gonadotropin (hCG) could improve endometrial receptivity. Therefore, we investigated the delivery of hCG to the endometrial cells by uterine exosomes to increase endometrial receptivity., Main Methods: Exosomes were isolated from uterine fluid and characterized by dynamic light scattering, transmission electron microscopy, and western blotting. The freeze-thaw cycle and sonication methods were used to load hCG into the exosomes. The drug release pattern and uptake of exosomes into the endometrial cells were evaluated. Finally, the influence of hCG loaded-exosomes on the expression of several endometrial receptivity markers was evaluated., Key Findings: The isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8 nm and zeta potential of -9.75 mV. The average loading capacity of exosomes for hCG was 710.05 ± 73.74 and 245.06 ± 95.66 IU/mg using the sonication and freeze-thaw cycle methods, respectively. The effect of hCG loaded-exosomes on the endometrial receptivity was greater than the hCG or exosomes alone. We found that hCG upregulated LIF and Trophinin and downregulated Muc-16 and IGFBP1 genes. Interestingly, the effect of hCG on the expression of LIF and Muc-16 was significantly intensified when used in the form of hCG loaded-exosomes., Significance: These findings strengthen our hope in using uterine fluid-derived exosome as an effective carrier for proteins or other therapeutic agents to effective delivery into endometrial cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Administration of platelet-rich plasma (PRP) is one of the well-recommended strategies for the treatment of endometrium- and ovary-associated infertility. Due to the autologous source of PRP, minimal risks for disease transmission and immunogenic and allergic responses are expected in this method. Despite the extensive use of PRP in medicine, its precise mechanism of action in endometrial and ovarian tissues is still unknown. Nevertheless, the induction of cell proliferation, chemotaxis, regeneration, extracellular matrix synthesis, remodeling, angiogenesis, and epithelialization are the main pathways for PRP to affect female reproductive organs. Given the promising results of previous studies, it is necessary to standardize PRP preparation protocols for different therapeutic purposes and also clearly determine appropriate inclusion and exclusion criteria for recruiting patients. In the current review, we presented a summary of studies on PRP therapy for endometrium- and ovary-associated infertility with a focus on the possible mechanisms by which PRP enhances endometrial receptivity and regenerates ovarian function. Abbreviations : PRP: platelet-rich plasma; ART: assisted reproductive technology; POF: premature ovarian failure; TGF: transforming growth factors; PDGF: platelet-derived growth factors; IGF-I: insulin-like growth factor-1; HGF: hepatocyte growth factor; EGF: epidermal growth factor; FGF: fibroblast growth factor; VEGF: vascular endothelial growth factor; ADP: adenosine diphosphate, ATP: adenosine triphosphate; PDGF: platelet-derived growth factor; COX2: cyclooxygenase-2; TP53: tumor protein 53; ER-α: estrogen receptors alpha; ER-β: estrogen receptors beta; PR: progesterone receptor; RIF: recurrent implantation failure; G-CSF: granulocyte colony-stimulating factor; iNOS: inducible nitric oxide synthase; NF-kβ: nuclear factor kappa beta; MMPs: matrix metalloproteinases; Col1a1: collagen type I alpha 1; IL: interleukin; FSH: follicle-stimulating hormone; AMH: anti-Mullerian hormone; GDF-9: growth differentiation factor 9.

Objectives: This study aimed to investigate the effectiveness of self-healing (the healing codes) intervention on quality of life (QoL) and mother-child interaction among female breadwinners., Methods: The study population comprised all female breadwinners who referred to the welfare centers of Isfahan in 2020; using convenience sampling, we selected 30 women and divided them into experimental and control groups (n = 15 per group). The experimental group underwent fourteen sessions (90-min sessions per week) of self-healing training., Results: The mean ± SD of QoL and mother-child interaction for experimental and control groups in the post-test stage were 84.33 ± 3.92 and 160.86 ± 8.74 respectively. Self-healing intervention had significant effects on QoL and mother-child interaction among female breadwinners. The intervention program improved the components of QoL and mother-child interaction among female breadwinners (p < 0.01)., Conclusions: Self-healing training can be used as a novel approach to enhance QoL and mother-child interaction in this group of women., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite performing certain morphological assessments for selecting the best embryo for transfer, the results have not been satisfactory. Given the global tendency for performing quick and noninvasive tests for embryo selection, great efforts have been made to discover the predictive biomarkers of embryo implantation potential. In recent years, many factors have been detected in embryo culture media as a major source of embryo secretions. Previous studies have evaluated cytokines, miRNAs, extracellular vesicles, and other factors such as leukemia inhibitory factor, colony-stimulating factor, reactive oxygen species, soluble human leukocyte antigen G, amino acids, and apolipoproteins in these media. Given the key role of cytokines in embryo implantation, these factors can be considered promising molecules for predicting the implantation success of assisted reproductive technology (ART). The present study was conducted to review embryo-secreted molecules as potential biomarkers for embryo selection in ART., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aim: Transforming growth factor β (TGF-β) and leucine-rich α-2-glycoprotein 1 (LRG1) play significant roles in the pathogenicity of uterine leiomyomas (ULMs). The current study aimed to assess the diagnostic values of serum TGF-β and LRG1 in terms of the presence and severity of ULMs., Methods: Premenopausal women with ULMs (n=44) together with age-adjusted ULM-free individuals (n=41) were incorporated into the study. ULMs were detected and evaluated using transvaginal ultrasonography. Serum levels of TGF-β and LRG1 were quantified by enzyme-linked immunosorbent assay., Results: Mean concentrations of serum TGF-β and LRG1 were significantly higher in the group of patients with ULMs compared to the control group (p<0.05). The volume of the largest leiomyoma was positively correlated with the levels of TGF-β (r = 0.414, p= 0.005) and LRG1 (r = 0.341, p= 0.023). The receiver-operating characteristics analysis demonstrated moderate and robust values of area under the curve for TGF-β (0.755) and LRG1 (0.90), respectively., Conclusion: Increases in serum levels of TGF-β and LRG1 is associated with the incidence and severity of ULMs. LRG1 in particular but also TGF-β may be able to serve as reliable biomarkers for the diagnosis and monitoring of ULMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Bacterial infection can negatively affect different parts of the male genital tract and subsequently cause impaired spermatogenesis and male fertility. However, most of the previous studies have focused on the infected organs of the male genital tract and there are not many studies that investigated the direct effect of bacteria on sperm and their mechanism of action. Interestingly, bacteria can induce different damages on sperm cells such as DNA fragmentation, cell membrane peroxidation, and acrosome impairment. Such negative effects can be mediated by bacteria-secreted toxins and metabolites or by direct attachment of bacteria on the sperm cells and subsequent activation of signaling pathways related to oxidative stress, apoptosis, and inflammation. These bacteria-induced changes can impair semen parameters and subsequently cause infertility. Given the significant destructive effect of some bacteria on sperm function and male fertility, in this study, we reviewed the impact of male urogenital bacteria on spermatogenesis and sperm functions as well as the underlying mechanisms by which the bacteria can damage sperm., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: The present study aimed to investigate the effect of self-healing training on self-compassion, body image concern, and recovery process in patients with skin cancer., Materials and Methods: The sample consisted of 34 volunteers who were purposefully selected and then randomly divided into experimental (n = 16) and control (n = 18) groups. The research instrument included the Self-Compassion Scale and Body Image Concern Inventory. The self-healing training intervention was then performed on the experimental group for twelve 90-min sessions. Finally, both groups underwent the post-test. Follow-up was performed two and four months after the post-test., Results: Self-healing training significantly increased self-compassion, including self-kindness, self-judgment, and sense of common humanity (p < 0.01), and decreased the level of body image concern, isolation, and over-identification (p < 0.05)., Conclusion: The self-healing is an appropriate intervention method to increase self-compassion and reduce body image concern and thus accelerate the process of skin cancer recovery., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Objectives: Stuttering is one of the most common speech disorders with many negative effects on children and their parents. The parents play a very important role in the treatment and management of children's stuttering. The parents' reactions to children's stuttering are pivotal in the exacerbation or improvement of stuttering. The present study aimed to investigate the parents' reactions to their children's stuttering using the Persian version of Reaction to Speech Disfluency Scale (RSDS)., Methods: The present study was conducted in two stages; phase 1: translation and cultural adaptation of RSDS into Persian and phase 2: investigation of the reaction of parents to children's stuttering using the RSDS. The first phase of the study included the following steps, forward translation, backward translation, content validity, face validity, and reliability of the scale using internal consistency and test-retest reliability. The second phase of the study was to examine the reactions of 110 parents of 3-6-year-old children who stutter by using the RSDS. Data were analyzed using SPSS software., Results: The results of translation and cultural adaptation of the RSDS showed that the Persian version of RSDS has suitable validity. The internal consistency (Cronbach's alpha = 0.94) and the test-retest reliability (ICC = 0.98) were also appropriate for this scale. The most reactions of parents to children's stuttering were cognitive, emotional, and behavioral, respectively. The results of evaluating the maternal and paternal reactions separately indicated that the highest value of paternal reaction score was cognitive, behavioral and emotional reactions, respectively, while the highest value of maternal reaction score was cognitive, emotional and behavioral reactions, respectively. Differences between fathers and mothers were statistically significant only in emotional reaction subscale (P < 0.001). The mean overall score of the RSDS for all parents was 29, as well as 27.72 and 30.27 in fathers and mothers groups, respectively, but this differences between groups not statistically significant (P = 0.12). Comparing the scores between parents of boys and girls who stutter showed that the mean overall scores of cognitive, emotional, and behavioral subscales, and overall scores in the parents of girls who stutter was higher than in the parents of boys who stutter, and this difference was statistically significant in the emotional subscale and the overall score between the two groups (P < 0.05)., Conclusion: The parental cognitive and behavioral reactions to children's stuttering had the maximum and minimum frequency, respectively. The paternal reactions to their children's stuttering were different from maternal reactions. The parents of girls who stutter in all subscales had a greater reaction compared to the parents of boys who stutter. Given the importance of the reactions of parents to their children's stuttering, the results of the present study can help to complete the information of therapists and researchers in this field., Competing Interests: Declaration of competing interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Exosomes, as lipid nanostructure, are secreted by approximately all cell types within the body and actively involved in either short or long distances cell-cell communication in an autocrine and paracrine manner. Recently, exosomes are widely used as a nanocarrier for delivery of various nucleotide- or protein passed molecules including miRNA, and drugs into various cells, as a therapeutic strategy in a broad range of diseases including osteoarthritis. Osteoarthritis is one of the most common debilitating chronic musculoskeletal disorders with a multifaceted condition and an increasing impact on the quality of life. Therefore, this review aims to focus on the current knowledge of the exosomal miRNAs in the osteoarthritis to address their potential therapeutic application.

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Paradoxical convergence movements on attempted side gaze have been rarely reported in horizontal gaze palsy. The authors report the clinical manifestation of right-sided facial colliculus syndrome in a 9-year-old girl who manifested convergence, miosis, and myopic shift on attempting right gaze that was treated with strabismus surgery, and provide a comprehensive literature review. [J Pediatr Ophthalmol Strabismus. 2020;57:e15-e18.]., (Copyright 2020, SLACK Incorporated.)

Introduction: Nowadays, mesenchymal stem cells are touted as suitable cell supply for the restoration of injured bone tissue. The existence of osteogenic differentiation makes these cells capable of replenishing damaged cells in the least possible time. It has been shown that epigenetic modifications, especially DNA methylation, contribute to the regulation of various transcription factors during phenotype acquisition. Hence, we concentrated on the correlation between the promoter methylation and the expression of genes DLX3, ATF4 , and FRA1 during osteoblastic differentiation of adipose-derived mesenchymal stem cells in vitro after 21 days. Methods: Adipose-derived mesenchymal stem cells were cultured in osteogenesis differentiation medium supplemented with 0.1 µM dexamethasone, 10 mM β-glycerol phosphate, and 50 µM ascorbate-2-phosphate for 21 days. RNA and DNA extraction was done on days 0, 7, 14, and 21. Promoter methylation and expression levels of genes DLX3 , ATF4 , and FRA1 were analyzed by methylation-specific quantitative PCR and real-time PCR assays, respectively. Results: We found an upward expression trend with the increasing time for genes DLX3, ATF4, and FRA1 in stem cells committed to osteoblast-like lineage compared to the control group ( P <0.05). On the contrary, methylation-specific quantitative PCR displayed decreased methylation rates of DLX3 and ATF4 genes, but not FRA1 , over time compared to the non-treated control cells ( P <0.05). Bright-field images exhibited red-colored calcified deposits around Alizarin Red S-stained cells after 21 days compared to the control group. Statistical analysis showed a strong correlation between the transcription of genes DLX3 and ATF4 and methylation rate ( P <0.05). Conclusion: In particular, osteoblastic differentiation of adipose-derived mesenchymal stem cells enhances DLX3 and ATF4 transcriptions by reducing methylation rate for 21 days., (© 2020 The Author(s).)

It is well known that embryo implantation is a critical process in which embryo should be able to reach and attach to endometrium. Until now, various types of factors are involved in the regulation of this process. S100 proteins are calcium-binding proteins, which have vital roles in embryo implantation and have been considered as possible candidate markers for endometrial receptivity. However, studies regarding mode of actions of these proteins are scarce and more mechanistic insights are needed to clarify exact roles of each one of the S100 protein family. Understanding of function of these proteins in different compartments, stages, and phases of endometrium, could pave the way for conducting studies regarding the therapeutic significance of these proteins in some disorders such as recurrent implantation failure. In this review, we outlined roles and possible underlying mechanisms of S100 protein family in embryo implantation., (© 2019 Wiley Periodicals, Inc.)

To evaluate the concentration of tumor necrosis factor α (TNF-α) and its soluble receptors (sTNFR I and II) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of TNF-α and its receptors by luteinized granulosa cells (GCs). In a cross-sectional study and through an in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) program, 81 women undergoing oocyte retrieval were recruited. Serum and FF were obtained from 81 women. GCs were pooled from 20 patients (from six different days of oocyte retrievals, 5-16 follicles per patient). TNF-α and its soluble receptors concentration were determined by enzyme-linked immunosorbent assay and also their expression by immune cytochemistry and reverse-transcription polymerase chain reaction analysis. The median TNF-α concentration in serum was 4.06 pg/ml (interquartile range [IQR], 3.71-6.14) and significantly higher than that in FF with 3.50 pg/ml (IQR, 3.05-5.01), p < 0.001. The sTNFR I and II levels in serum were lower and higher than FF, respectively. The TNF-α levels in serum and FF of good responders were higher than low responders (p = 0.017 and 0.021, respectively). TNF-α cut-off level for low responders versus good responders was 4.174 pg/ml in serum with a pregnancy rate of 25.8% and 40% for below and above of this level, respectively (p = 0.19). For FF, the cut-off value was 3.89 pg/ml. TNF-α and its receptors were expressed by GCs. The presence of TNF-α and its soluble receptors in serum and FF and their expression by GCs suggest an important role for this cytokine in ovarian function., (© 2019 Wiley Periodicals, Inc.)

Different strategies are applied for cellular cross-talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30-100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome-based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology., (© 2019 Wiley Periodicals, Inc.)

As a critical stage of pregnancy, the implantation of blastocysts into the endometrium is a progressive, excessively regulated local tissue remodeling step involving a complex sequence of genetic and cellular interplay executed within an optimal time frame. For better understanding the causes of infertility and, more importantly, for developing powerful strategies for successful implantations and combating infertility, an increasing number of recent studies have been focused on the identification and study of newly described substances in the reproductive tree. The endothelins (ET), a 21-aminoacidic family of genes, have been reported to be responsible for the contraction of vascular and nonvascular smooth muscles, including the smooth muscles of the uterus. Therefore, this review aims to comprehensively discuss the physiological role of endothelins and signaling through their receptors, as well as their probable involvement in the implantation process., (© 2019 Wiley Periodicals, Inc.)

Purpose: No comprehensive information is available about uterus fatty acid (FA) change during implantation period and possible effects of the seminal vesicle secretion on it., Materials and Methods: In this study, we evaluated FA composition of uterus phospholipids during the implantation period in intact and seminal vesicle-excised (SVX) mated female mice. Forty NMRI female mice were divided into control (mated with intact male) and seminal vesicle excised (SVX)-mated (mated with SVX-male) groups. The phospholipid fatty acids composition was monitored during the fi rst fi ve days of pregnancy using gas chromatography and also implantation rate was evaluated on fi fth day of pregnancy., Results: We found that levels of linoleic acid (LNA) and arachidonic acid (ARA) showed a decreasing trend from the fi rst to the third day of pregnancy and then started to increase on the fourth day and peaked on the fi fth day. In contrast, the level of saturated FA (SFA) increased on the second and third day of pregnancy compared to the fi rst (p<0.05) and then decreased on the fourth and fi fth. We also found that the seminal vesicle secretion could affect the levels of LNA, ARA, SFA, and PUFA in uterine phospholipids especially on second and third day. Moreover, there was a positive correlation between ARA level and implantation rate in control but not SVX-mated groups., Conclusions: It can be concluded that several uterus FA that have important roles in early pregnancy could be affected by seminal vesicle secretion., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

TGF-β signaling in the endometrium is active during the implantation period and has a pivotal role in regulating endometrial receptivity and embryo implantation. During embryo implantation, both apoptosis and proliferation of endometrial cells happen at the same time and it seems TGF-β is the factor that controls both of these processes. As shown in cancer cells, in special conditions this cytokine can have a dual effect and switch the action from apoptosis to proliferation. Owing to the similarity between embryo implantation and cancer development and also unusual pattern of proliferation and remodeling in the uterus, in this review we suggest the existence of such a switching in endometrium during the early pregnancy. Moreover, we address some potential mechanisms that could regulate the switching. A better understanding of the molecular mechanisms regulating TGF-β action and signaling during the implantation period could pave the way for introducing novel therapeutic strategies in order to solve implantation-associated issues such as repeated implantation failure., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high-density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein-coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target., (© 2018 Wiley Periodicals, Inc.)

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and - 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%. Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.

The recent investigations have extensively focused on the importance of sirtuins, as a highly conserved family of gene products, particularly SIRT3 in various biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent deacetylase has been demonstrated to target a broad range of proteins involved in the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. The critical function of SIRT3 in myocardial infarction (MI), which is one of the complex phenotype of coronary artery disease and a result of interaction between various genetic and environmental factors, as well as in cardiac repair and remodeling post-MI have attracted more attention in the recent years. Therefore, in this review, we will summarize important literature about the involvement of SIRT3 in cardiac remodeling/repair following MI and its potential underlying mechanisms., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The application of mineral fertilizers which have contaminants of trace elements may impose concern regarding the entry and toxic accumulation of these elements in agro-ecosystems. In this study, 57 mineral fertilizers (nitrogen, potassium, phosphate, and compound fertilizers) distributed in Iran were analyzed for their contents of Cd, Co, Cr, Cu, Mn, Ni, Pb, Zn, and Fe. The results revealed that the contents of these trace elements varied considerably depending on the type of the element and the fertilizer. Among these elements, Fe displayed the highest average content, whereas Cd showed the lowest. Generally, the trace element contents in P-containing fertilizers were higher than those in nitrogen and potassium fertilizers. The mean values of trace elements (mg kg -1 ) in P-containing fertilizers were 4.0 (Cd), 5.5 (Co), 35.7 (Cr), 24.4 (Cu), 272 (Mn), 14.3 (Ni), 6.0 (Pb), 226 (Zn), and 2532 (Fe). Comparing trace element contents to limit values set by the German Fertilizer Ordinance showed that the mean contents of potentially toxic trace elements, such as Cd and Pb, were lower than their limit values in all groups of fertilizers. On the other hand, while a number of fertilizers contained a high content of some essential trace elements, particularly Fe, they were not labeled as such.

Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N-methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1-methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti-inflammatory and anti-thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions., (© 2018 Wiley Periodicals, Inc.)

Considering possible effects of poly-unsaturated fatty acids (PUFA) on embryo implantation more likely through PGs, we investigated effects of dietary omega-3 and -6 PUFA on prostaglandin E2 (PGE2) signaling in mice uterus during pre-implantation period. The mRNA expressions of microsomal- and cytosolic- PGE synthase (mPGES and cPGES) and protein expressions of PGE receptor 2 and 4 (EP2 and EP4) were evaluated in uterus tissues of control as well as omega 3 and omega 6 received mice at days 1-5 of pregnancy. Expression of cPGES gene was not significantly different between groups but the mPGES expression on days 4 and 5 of pregnancy in supplemented groups was higher than controls. Omega-3 significantly decreased EP2 levels on days 3 and 4, while omega-6 caused an increase on days 3-5 of pregnancy. The levels of EP4 were significantly higher in the omega-6 group than other groups on days 4 and 5 of pregnancy. Also the implantation rate was higher in omega -6 compared to omega-3 group (p = 0.006). Moreover, there were significant correlations between implantation rate with expression levels of mPGES and EP2. Our results showed negative and positive effects of respectively dietary omega-3 and -6 PUFA on PGE2 signaling and implantation rate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi-allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti-paternal cytotoxic antibodies (APCA), progesterone-induced blocking factor (PIBF), anti-idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR-Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

During embryo implantation, crosstalk between the endometrial epithelium and the blastocyst, especially the trophoblasts, is a prerequisite for successful implantation. During this crosstalk, various molecular and functional changes occur to promote synchrony between the embryo and the endometrium as well as the uterine cavity microenvironment. In the past few years, growing evidence has shown that endometrium-derived exosomes play pivotal roles in the embryonic-maternal crosstalk during implantation, although the exact mechanism of this crosstalk has yet to be determined. The presence of metalloproteinases has been reported in endometrium-derived exosomes, implying the importance of these enzymes in exosome-based crosstalk. Thus, in this review, we describe the potential roles of the metalloproteinases of endometrium-derived exosomes in promoting embryo attachment and implantation. This study could provide a better understanding of the potential roles of exosomal metalloproteinases in embryo implantation and pave the way for developing novel exosome-based regulatory agents to support early pregnancy., (© 2017 Wiley Periodicals, Inc.)

Introduction: The importance of seminal vesicle secretion and uterine Wnt signaling for uterus preparation and embryo implantation has been described., Materials and Methods: In this study, we evaluated the gene expression of Wnt ligands (Wnt4 and Wnt5a) and their corresponding receptors (Fzd2 and Fzd6) using qRT-PCR and active β-catenin protein levels using western blotting in the uterine tissue of female mice mated with intact and seminal vesicle-excised (SVX) males during the pre-implantation window. We evaluated the association between these factors and implantation rates and embryo spacing., Results: mRNA expression of Wnt4 and Wnt5a and active β-catenin protein levels decreased from Day 1 to Day 4, but reached a peak on the fifth day of pregnancy. Fzd2 also reached its highest level on Day 5. Fzd6 expression showed a decreasing trend towards the day of implantation. Lack of seminal vesicle secretion decreased Wnt4 and Wnt5a expression on Days 1 and 5 and β-catenin levels on Day 5. There were almost no significant differences in expression levels of the Fzd2 and Fzd6 receptors between groups. There were positive and negative correlations, respectively, between implantation rates and embryo spacing and Wnt4, Wnt5a and active β-catenin in the control group, but such correlations were not observed in the SVX-mated mice., Conclusions: Significant changes occurred in the expression of several Wnt signaling members and there was a significant association between Wnt signaling and embryo implantation. Seminal vesicle secretion affects Wnt signaling in mice and consequently also affects murine embryo implantation.

Prostaglandin E 2 (PGE 2 ) has been introduced as an important factor for embryo implantation. So the present study was carried out to evaluate the effect of seminal fluid (SF) on PGE 2 pathway in uterus tissues of mice during window of preimplantation. The messenger RNA (mRNA) expressions of microsomal PGE synthase (mPGES) and cytosolic PGE synthase (cPGES) as well as protein expression of PGE receptor 2 and 4 (EP2 and EP4) were determined in uterine tissue of control and seminal vesicle-excised (SVX)-mated female mice during days 1 to 5 of pregnancy using real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. We found that mRNA expression of mPGES at day 1 and 2 of pregnancy was significantly higher in the control group than the SVX-mated group ( P < .05), but such result was not obtained for cPGES expression. The protein levels of EP2 at day 1 to 4 of pregnancy were significantly higher in the control group compared with the SVX-mated group ( P < .05), also the EP4 levels were significantly different between the control and SVX-mated groups at the first day of pregnancy ( P < .05). Implantation rate was higher in the control group and also there were positive correlations between mPGES and EP2 expressions in the fifth day of pregnancy with implantation rate. Our results demonstrated significant effect of SF on uterine expressions of the evaluated factors, especially mPGES and EP2. Regarding the correlations between levels of these factors and implantation rate, we suggest that possibly one of the important mechanisms of SF in affecting female pregnancy is through mPGES and EP2.

Sulfur mustard (SM) is an alkylating agent that causes severe damages to the skin, eyes, and the respiratory system. DNA alkylation is one of the most critical lesions that could lead to monoadducts and cross-links, as well as DNA strand breaks. In response to these adducts, cells initiate a series of reactions to recruit specific DNA repair pathways. The main DNA repair pathways in human cells, which could be involved in the DNA SM-induced DNA damages, are base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). There is, thus, a need for a short review to clarify which damage caused by SM is repaired by which repair pathway. Increasing our knowledge about different DNA repair mechanisms following SM exposure would lay the first step for developing new therapeutic agents to treat people exposed to SM. In this review, we describe the major DNA repair pathways, according to the DNA adducts that can be caused by SM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Since fatty acid composition of uterus phospholipids is likely to influence embryo implantation, this study was conducted to investigate the effects of dietary omega-3 and -6 fatty acids on implantation rate as well as uterine phospholipid fatty acids composition during mice pre-implantation period. Sixty female mice were randomly distributed into:1) control (standard pellet), 2) omega-3 (standard pellet + 10% w/w of omega-3 fatty acids) and 3) omega-6 (standard pellet + 10% w/w of omega-6 fatty acids). Uterine phospholipid fatty acid composition during the pre-implantation window (days 1-5 of pregnancy) was analyzed using gas-chromatography. The implantation rate on the fifth day of pregnancy was also determined. Our results showed that on days 1, 2 and 3 of pregnancy, the levels of arachidonic acid (ARA) as well as total omega-6 fatty acids were significantly higher and the levels of linolenic acid and total omega-3 fatty acids were statistically lower in the omega-6 group compared to the omega-3 group (p < 0.05). On the fourth day of pregnancy, only the ARA, total omega-6 fatty acids, and poly-unsaturated fatty acids levels were significantly different between the two dietary supplemented groups (p < 0.05). There were positive correlations between the levels of omega-6 fatty acids, especially ARA, with the implantation rate. The present study showed that diets rich in omega-3 and -6 fatty acids could differently modify uterine phospholipid fatty acid composition and uterine levels of phospholipid ARA, and that the total omega-6 fatty acids had a positive association with the implantation rate., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Seminal plasma (SP) is considered as a vehicle to carry sperm into female reproductive tract, of which functions have not been completely understood. This study aimed to identify the function of seminal exosomes on porcine endometrium. Exosomes were isolated from the sperm-rich fraction of boar semen and were confirmed by the expression of exosome marker HSP70 and size distribution using nano-sight tracking analysis. Porcine endometrial epithelial cells (EECs) were then treated with seminal exosomes, and RNA extracted were subjected to global expression analysis. Transcripts related to "immune response", "inflammatory response" and their associated signaling pathways were up-regulated in EECs treated with seminal exosome, whereas those associated with "steroid biosynthesis", "metabolic pathways" and "T cell differentiation" were down-regulated. The decrease in PMVK, SC5D, INSIG1, HSD17B7, NSDHL, HMGCR, SQLE and FDFT1, and increase in CCL20, TNFSF15, AMCFII, CXCL2 and CXCL8 were also found in the endometrium from the naturally mated pigs. Moreover, changes in exosome-induced CYP24A1, EBP, CCL20, AMCFII and IL1A expression were not regulated by the exosome removed SP. These observations indicated that exosomes present in SP are involved in the immune-related gene regulation in the uterus, which could pave the passage for sperm and possibly fertilized eggs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.

Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies have pointed out the possibility of stem cell-derived sperm production. Most studies that test this hypothesis have been conducted on rodents, with some promising results; however, studies on humans are progressing slowly, and have encountered technical and ethical hurdles. Established methods to differentiate stem cells-including embryoid bodies, co-culturing, and various feeder cells-may provide a niche that is similar to in vivo conditions and resolve epigenetic abnormalities, but a gonadal-like three-dimensional structure is still required to produce germ cells with the correct imprinting. In the last few years, sperm-like cells with fertilizing capacity were produced from mouse embryonic stem cells, and the resulting embryos from these cells yielded live offspring. Future research should move towards the use of adult stem cells, however, owing to the unavailability of embryonic cells in adults. More intensive research and techniques are required since in vitro spermatogenesis provides hope to individuals without mature sperm who cannot be treated, and may be a useful system to study the precise mechanism of spermatogenesis. In this review, we describe recent studies of in vitro spermatogenesis mechanisms and related techniques in mammals. We also discuss the possible cell surface markers and culture conditions that might improve in vitro spermatogenesis., (© 2017 Wiley Periodicals, Inc.)

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor ( P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower ( P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions.

Objective: To evaluate frequency distribution of adenosine deaminase 1 (ADA1) G22 A alleles and genotypes in fertile and infertile men., Methods: In this study we evaluate frequency distribution of ADA1 G22 A alleles and genotypes in 200 fertile and 200 infertile men. The polymerase chain reaction-restriction fragment length polymorphism technique was used for determining ADA1 G22 A variants. In addition, ADA isoenzymes activities (ADA1 and ADA2) were measured using colorimetric method., Results: The frequency of GG genotype was significantly higher and GA genotype was lower in infertile males compared with fertile men (P = .048 and P = .045, respectively). However, there was not any noticeable difference in allele distribution between groups (P >.05). Based on logistic regression analysis, the GA genotype has a protective role and can decrease the risk of male infertility 1.7 times (P = .046). There were significantly higher activities of ADAT and its isoenzymes in infertile males compared with fertile men (P <.05). Also, the ADA1 activity with GG genotype was higher than GA carriers in all population (P = .001)., Conclusion: Our results revealed that the activity of ADA isoenzymes and distribution of ADA1 G22 A genotypes were different among fertile and infertile men and more likely the GA genotype, which had lower ADA1 activity and was higher in fertile men is a protective factor against infertility., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Vitamin D in complex with its receptor by regulating gene expression, endometrium immune response and stimulation of endometrium decidualization can be involved in implantation. So, it seems that the amount of vitamin D in follicular fluids (FF) may have an association with ART success., Objective: First, we intended to investigate the possible association between levels of follicular fluids 25-OH vitamin D with assisted reproductive outcomes. Second, we examined relationship between 25-OH vitamin D levels with number and quality of oocytes., Materials and Methods: In a prospective study, 80 infertile female candidates for IVF/ICSI were enrolled. Blood samples (on the day of human chorionic gonadotropin administration) and follicular fluids were taken, and then levels of serum estradiol and follicular fluids 25-OH vitamin D were measured. Also clinical characteristics of patients (duration of infertility, causes of infertility, menstrual status), number and quality of oocytes, number of fertilized oocytes, estradiol levels, and clinical pregnancy were evaluated., Results: Concentration of FF 25-OH vitamin D in pregnant women was significantly higher than non-pregnant women (p=0.007) but there were no significant differences in age, body mass index (BMI), duration of infertility, menstrual status, number of oocytes, oocytes quality, number of fertilized oocytes, and serum estradiol levels between the two groups. Statistically positive correlation was found between 25-OH vitamin D levels with patient age and implantation rate (r=0.264, p=0.018 and r=0.301, p=0.007 respectively)., Conclusion: The obtained results suggest that vitamin D without affecting the number and quality of oocytes can independently improve implantation rate and IVF outcome.