Effect of dietary approaches to stop hypertension, and standard diets with and without curcumin on interleukin-1 alpha, 5-alpha reductase gene expressions, and androgenic and glycemic profile in polycystic ovary syndrome women undergoing in vitro fertilization treatment: A study protocol.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases with major reproductive and metabolic complications with an impact on public health. Hyperandrogenism and chronic inflammation have been suggested as the leading cause of pathophysiology and clinical manifestations associated with PCOS. It seems that the altered expression of genes involved in the synthesis of pro-inflammatory cytokine and androgens contribute to the promotion of PCOS. Objective: This trial aims to determine the effects of dietary approaches to stop hypertension (DASH) and standard diets with and without curcumin supplementation on the gene expression of interleukin -1 alpha(IL1α), 5α reductase and androgenic and glycemic profile among PCOS patients, who are candidates for in vitro fertilization. Materials and Methods: 96 infertile women with PCOS, aged 18-40 yr, will participate in this randomized, placebo-controlled clinical trial. Based on treatment conditions and body mass index, the participants will be randomly divided into 4 equal groups using a randomized block design. They will receive a DASH or standard diet containing 52% carbohydrate, 18% protein, and 30% total fat, with the same prescribed sodium, plus 500 mg twice daily curcumin or placebo for 12 wk. The mRNA expression of IL-1α, 5α reductase, and androgenic and glycemic profiles will be measured at baseline and at the end of the study. Conclusion: Concomitant administration of DASH diet and curcumin supplementation may reduce IL-1α, 5α reductase gene expressions, and improve glycemic and androgenic profiles.

Is sperm telomere length altered in teratozoospermia specimens? A case-control study.

Background: Male factor infertility is a multifactorial defect, and many of its etiologies are unknown. Teratozoospermia is determined by the existence of over 85% morphologically abnormal spermatozoa in semen which are almost incompetent in fertilization function. One of the most novel issues in genetic alterations studies is the variation of sperm telomere lengths (STL) and its collaboration with male infertility. The present study has been focused on STL alterations in teratozoospermia. Objective: Investigation of differences in telomere length of teratozoospermia specimens and sperms with normal parameters. Materials and Methods: In this case-control study, 60 men referred to Arak Fertility Clinic, Markazi province, Iran from November 2017 to February 2018 were categorized into teratozoospermia and normozoospermic groups. Sperm genomic DNA extraction was conducted, and STL were evaluated using quantitative polymerase chain reaction. Results: Statistical evaluation of relative telomere length was calculated by the ratio of telomere to single-copy gene for teratozoospermia and normal specimens. Results significantly demonstrated that relative telomere length in teratozoospermia samples is nearly 3 times shorter than in normal samples (p > 0.001). Conclusion: Our results represent the reduction of telomeres length in teratozoospermia and suggest that this alteration might be one of the factors contributing to the sperm fertility potential of this kind of specimen. However, defining relevant molecular processes requires further detailed investigations.

Possible Harmful Effects of Smoking Hookah on Sperm DNA Fragmentation Index and Protamine Genes Expression in Normozoospermic Men.

Objectives: In recent years, smoking water pipes or hookah has increased among adolescents in most countries. Although there is evidence in support of the negative effects of this type of smoking on human health, such as the increased risk of lung disease, little is known about the potential effects of hookah smoking on the male reproductive system, especially on the molecular aspects of sperm. Patients and methods: This cross-sectional study examined sperm DNA fragmentation index, protamine 1 and 2 (PRM1 and PRM2) genes expression, and oxidant status in normozoospermic hookah smokers in comparison with non-smoker controls. Results: Our results showed significantly higher rates of DNA fragmentation, protamine deficiency, and abnormal chromatin condensation in the spermatozoa of hookah smokers (P < .0001). Also, protamine gene expression showed a remarkable decrease in hookah smokers (1.55 ± 2.54 and 0.33 ± 0.54) compared to the controls (3.49 ± 5.41 and 1.22 ± 1.96), although the reduction was not statistically significant (P = .155 and P = .066, respectively). Moreover, a significantly higher level of semen MDA was observed in the case group compared to the controls (0.39 ± 1.04 vs 0.15 ± 0.21; P = .013). Conclusion: According to our study, although hookah smoking does not have a significant effect on sperm parameters, it may have deleterious effects on DNA integrity, oxidative status, and nuclear protein levels of spermatozoa.

Evaluation of CAG repeat length in the androgen receptor gene and polycystic ovary syndrome risk in Iranian women: A case-control study.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, which affects about 15-20% of women of reproductive age. The most important etiopathogenesis factor in its incidence is hyperandrogenism; over 70 candidate genes are known to be associated with this syndrome, such as the androgen receptor (AR) gene which encodes a steroid receptor and is located on the Xq11-12 chromosome. The N-terminus of exon 1 of AR contains a polymorphic trinucleotide repeat (CAG)n region that encodes glutamine tract. There are some studies showing that shorter AR CAG repeats are significantly related to enhanced AR sensitivity. Objective: This study investigated the frequency of the polymorphic expansion of the trinucleotide CAG repeats of AR in PCOS. Materials and Methods: 160 Iranian women aged 17-40 yr participated in this case-control study: 80 women as PCOS patients and 80 women as healthy controls according to the Rotterdam criteria. Other similar phenotype factors such as hyperandrogenism were not considered as PCOS. The frequency of polymorphic expansion of CAG trinucleotide repeats in PCOS patients was compared with the frequency in non-PCOS controls in using two primer sets for nested polymerase chain reaction. The polymerase chain reaction products were visualized on polyacrylamide gel and then were confirmed by a sequencing process. Results: The results did not show a significant correlation between the frequency of CAG repeats in AR and PCOS incidence. Conclusion: In contrast to some previous reports, the present data showed that the CAG length in PCOS cases did not significantly differ from that of controls. So, the AR (CAG)n does not appear to be a major factor for PCOS in Iranian women.

Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development.

Receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein taken in diverse chronic inflammatory conditions. RAGE behaves as a pattern recognition receptor, which binds and is engaged in the cellular response to a variety of damage-associated molecular pattern molecules, as well as HMGB1, S100 proteins, and AGEs (advanced glycation end-products). The RAGE activation turns out to a formation of numerous intracellular signaling mechanisms, resulting in the progression and prolongation of colorectal carcinoma (CRC). The RAGE expression correlates well with the survival of colon cancer cells. RAGE is involved in the tumorigenesis, which increases and develops well in the stressed tumor microenvironment. In this review, we summarized downstream signaling cascade activated by the multiligand activation of RAGE, as well as RAGE ligands and their sources, clinical studies, and tumor markers related to RAGE particularly in the inflammatory tumor microenvironment in CRC. Furthermore, the role of RAGE signaling pathway in CRC patients with diabetic mellitus is investigated. RAGE has been reported to drive assorted signaling pathways, including activator protein 1, nuclear factor-κB, signal transducer and activator of transcription 3, SMAD family member 4 (Smad4), mitogen-activated protein kinases, mammalian target of rapamycin, phosphoinositide 3-kinases, reticular activating system, Wnt/ß-catenin pathway, and Glycogen synthase kinase 3ß, and even microRNAs.

Investigating the rate of different ovarian response in in vitro fertilization cycles based on estrogen receptor beta +1730 polymorphism: A cross-sectional study.

BACKGROUND: The response to ovarian stimulation is different among women referring for assisted reproductive techniques. This difference could be due to different genotypes in genes related to reproduction such as estrogen receptor beta (ERß or ESR2) gene. OBJECTIVE: In the present study, we explored the rate of ESR2 gene polymorphism in infertile women undergoing IVF treatment with different ovarian response to ovulation induction. MATERIALS AND METHODS: A cross-sectional study was performed among 91 infertile women. The relationship between genotype distribution of the +1730 G/A polymorphism in the ESR2 gene (rs4986938) and the mean number of follicles and oocytes, their mean ratio, mean number of embryos, mean size of the follicles and pregnancy rates were measured. The ESR2 gene +1730 G/A polymorphism were identified by the amplification-refractory mutation system-polymerase chain reaction. RESULTS: Genotypes GG, GA, and AA of the ESR2 gene presented frequencies of 27.5%, 67%, and 5.5%, respectively, in the infertile women. The results of the study showed that the mean number of follicles and oocytes, their mean ratio, mean number of embryos, mean size of the follicles, and pregnancy rates are not related to different genotypes. CONCLUSION: According to the endocrine and paracrine factors which are involved in the ovulation induction and maturation of oocytes, more studies with higher number of participants are required to confirm the results of the present study; in addition, further studies are required to find out other gene polymorphisms affecting estrogen receptor efficacy in the infertile women.

Expression levels of circulatory mir-185-5p, vascular endothelial growth factor, and platelet-derived growth factor target genes in endometriosis.

BACKGROUND: Using blood-based biomarkers such as microRNAs (miRNAs) may allow particularly effective and minimally invasive diagnosis and treatment of endometriosis. Objective: We evaluated the differential expression of circulating miRNA-185-5p (miR-185-5p), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) target genes between endometriosis and healthy women. MATERIALS AND METHODS: 25 women with a history of endometriosis (grad III-IV) diagnosed by laparoscopy as the case group and 25 women without endometriosis underwent laparoscopy for ovarian cysts or pelvic pain as the control group were enrolled in this case-control study. Blood samples were obtained, and total RNA was used for high-throughput small RNA sequencing, and this was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: miRNA expression profiling using non-coding RNA sequencing revealed that one miRNA including miR-185-5p was significantly down-regulated in the case group compared with the controls. The qRT-PCR results showed significant downregulation of the expression level of miR-185-5p (p < 0.01) in the plasma of the case group. Receiver operating characteristic (ROC) curve analysis showed the area of miR-185-5p under the ROC curve for endometriosis diagnosis was 0.919 (p < 0.001). The RT-PCR results demonstrated that there was no significant difference in the expression of VEGF and PDGF mRNA of blood samples in the cases compared to the control group (PDGF, p = 0.09 and VEGF, p = 0.36). CONCLUSION: The low expression of miR-185-5p in the plasma of women with endometriosis could be employed as an important non-invasive biomarker for early detection and screening of endometriosis by blood samples.