In vitro effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of genes related to sperm motility and energy metabolism and intracytoplasmic sperm injection outcomes in obstructive azoospermic patients.

BACKGROUND: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. METHODS AND RESULTS: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). CONCLUSIONS: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes.

Birth prevalence of genital anomalies among males conceived by intracytoplasmic sperm injection cycles: A cross-sectional study.

Background: Several studies have been conducted worldwide to evaluate the prevalence and relative risks of congenital anomalies associated with assisted reproductive technology cycles; however, there is limited data in Iran. Objective: To investigate male genital anomalies among live births from assisted reproductive technology. Materials and Methods: This cross-sectional study was conducted on children born after intracytoplasmic sperm injection (ICSI) at Royan Institute, Tehran, Iran from April 2013-December 2015. The prevalence of male genitalia disorders that included hypospadias, epispadias, cryptorchidism, micropenis, and vanishing testis were reported. The relationship between the cause of infertility and type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and birth weight with these male genitalia anomalies were evaluated. Results: In total, 4409 pregnant women were followed after their ICSI cycles to evaluate genitalia anomalies in their children. Out of 5608 live births, 2614 (46.61%) newborns were male, of which 14 cases (0.54%) had genital anomalies. The prevalence of various anomalies were cryptorchidism (0.34%), hypospadias (0.038%), micropenis (0.038%), vanishing testis (0.038%), and epispadias (0.077%). No relationship was found between the cause of infertility, type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and male genital malformation (p = 0.33, p = 0.66, and p = 0.62, respectively). Conclusion: The prevalence of each male genital anomaly after the ICSI cycle was rare and less than 0.5%; however, no significant infertility-related factor was observed with these anomalies.

Evaluation of polyglycolic acid as an animal-free biomaterial for three-dimensional culture of human endometrial cells.

OBJECTIVE: Animal-free scaffolds have emerged as a potential foundation for consistent, chemically defined, and low-cost materials. Because of its good potential for high biocompatibility with reproductive tissues and well-characterized scaffold design, we investigated whether polyglycolic acid (PGA) could be used as an animal-free scaffold instead of natural fibrin-agarose, which has been used successfully for three-dimensional human endometrial cell culture. METHODS: Isolated primary endometrial cells was cultured on fibrin-agarose and PGA polymers and evaluated various design parameters, such as scaffold porosity and mean fiber diameter. Cytotoxicity, scanning electron microscopy (SEM), and immunostaining experiments were conducted to examine cell activity on fabricated scaffolds. RESULTS: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and SEM results showed that endometrial cells grew and proliferated on both scaffolds. Immunostaining showed cytokeratin and vimentin expression in seeded cells after 7 days of culture. On both scaffolds, an epithelial arrangement of cultured cells was found on the top layer and stromal arrangement matrix on the bottom layer of the scaffolds. Therefore, fibrin-agarose and PGA scaffolds successfully mimicked the human endometrium in a way suitable for in vitro analysis. CONCLUSION: Both fibrin-agarose and PGA scaffolds could be used to simulate endometrial structures. However, because of environmental and ethical concerns and the low cost of synthetic polymers, we recommend using PGA as a synthetic polymer for scaffolding in research instead of natural biomaterials.

Multivariate Gaussian Copula Mutual Information to Estimate Functional Connectivity with Less Random Architecture.

Recognition of a brain region's interaction is an important field in neuroscience. Most studies use the Pearson correlation to find the interaction between the regions. According to the experimental evidence, there is a nonlinear dependence between the activities of different brain regions that is ignored by Pearson correlation as a linear measure. Typically, the average activity of each region is used as input because it is a univariate measure. This dimensional reduction, i.e., averaging, leads to a loss of spatial information across voxels within the region. In this study, we propose using an information-theoretic measure, multivariate mutual information (mvMI), as a nonlinear dependence to find the interaction between regions. This measure, which has been recently proposed, simplifies the mutual information calculation complexity using the Gaussian copula. Using simulated data, we show that the using this measure overcomes the mentioned limitations. Additionally using the real resting-state fMRI data, we compare the level of significance and randomness of graphs constructed using different methods. Our results indicate that the proposed method estimates the functional connectivity more significantly and leads to a smaller number of random connections than the common measure, Pearson correlation. Moreover, we find that the similarity of the estimated functional networks of the individuals is higher when the proposed method is used.

GM-CSF (granulocyte-macrophage colony-stimulating factor) treatment improves sperm parameters in men with oligoasthenoteratospermia via PI3K/AKT pathway.

Poor sperm quality in oligoasthenoteratospermia patients negatively affects assisted reproductive technology outcomes. Therefore, the development of sperm media is necessary to improve sperm parameters. This study investigated the effect of GM-CSF via PI3K/AKT pathway on sperm quality in OAT patients. Semen samples were collected from 20 OAT patients, and each sample was divided into two groups: Experiment and Control. In the experimental group, the samples were incubated with medium containing GM-CSF, and control samples were incubated without GM-CSF. Sperm parameters, mitochondrial membrane potential, acrosome reaction and DFI were studied; in addition, gene expression of PI3KR1, PI3KCA, GLUT1, GLUT3 and AKT1 was analysed, evaluation of PAKT/TAKT, and expression of GLUT 1, 3 was examined; subsequent fertilization rate and embryo quality were assessed. Our data showed that GM-CSF supplementation could significantly increase motility, mitochondrial activity, gene expression of PI3KCA, AKT1, the protein level of PAKT/TAKT and expression of GLUT 1, 3 while it decreases DNA fragmentation. The fertilization rate and embryo quality significantly improved in the treatment group. LY294002 had adverse effects on sperm motility and the PAKT/TAKT ratio. GM-CSF can improve in vitro sperm quality and could be a suitable supplement to sperm media for OAT patients.

Does prevalence of sexual dysfunction differ among the most common causes of infertility? A cross-sectional study.

BACKGROUND: Sexuality as a fundamental component of women's health, can be affected by infertility. The current study aimed at comparing the prevalence of sexual dysfunction among women with the most common causes of infertility. METHODS: The current cross-sectional study was conducted on 240 infertile females with infertility due to polycystic ovary syndrome (PCOS, n = 80), endometriosis (n = 80) and male factor (n = 80) at Royan Institute for Reproductive Biomedicine (Tehran, Iran) and 160 fertile women at health care centers, between May 2016 and June 2017. Sexual function was assessed by Female Sexual Function Index (FSFI). Data were analyzed using SPSS (version 25.00) and differences were regarded statistically significant at p < 0. 05. RESULTS: The prevalence of female sexual dysfunction was 98.8% in women with PCOS, 100.0% in those with endometriosis, and 80.0% in those with male factor infertility. Overall, 36.2% of the enrolled fertile women were suffering from sexual dysfunction. CONCLUSIONS: There was an association between the prevalence of female sexual dysfunction or individual domain scores of the FSFI, and infertility etiologies. Therefore, infertility care providers are required to take this into consideration and develop preventive strategies in this regard. Infertility as a major health care problem affects an estimated 8-12% of couples of reproductive age globally and sexuality as an important part of women's health, can be affected by infertility. In this study, the prevalence of sexual dysfunction among women with the most common causes of infertility has been evaluated. The present study was conducted on 240 infertile females with infertility due to polycystic ovary syndrome (PCOS, n = 80), endometriosis (n = 80) and male factor (n = 80) at Royan Institute (Tehran, Iran) and 160 fertile women at health care centers, between May 2016 and June 2017. Sexual function was assessed by Female Sexual Function Index (FSFI); a brief self-report measure of sexual functioning. Results highlight that the prevalence of sexual dysfunction in women with endometriosis and PCOS was higher than in other groups. As, the prevalence of female sexual dysfunction was 98.8% in women with PCOS, 100.0% in those with endometriosis, and 80.0% in those with male factor infertility. In total, 36.2% of the enrolled fertile women were suffering from sexual dysfunction. The results point to an association between the prevalence of female sexual dysfunction and causes of infertility. Therefore, infertility care providers are required to take this into consideration and develop preventive strategies in this regard.

The boosting effects of melatonin on the expression of related genes to oocyte maturation and antioxidant pathways: a polycystic ovary syndrome- mouse model.

BACKGROUND: Melatonin, as a free radical scavenger exhibiting genomic actions, regulates the antioxidant genes expression and apoptosis mechanisms. In polycystic ovary syndrome (PCOS) patients, an imbalance between free radicals and antioxidants in follicular fluid leads to oxidative stress, aberrant folliculogenesis, and intrinsic defects in PCOS oocytes. In this experimental mouse model study, oocytes of PCOS and the control groups were cultured in different melatonin concentrations (10- 5, 10- 6, and 10- 7 M) to investigate the expression of oocyte maturation-related genes (Gdf9/Bmp15), antioxidant-related genes (Gpx1/Sod1), apoptotic biomarkers (Bcl2/Bax) and total intracellular ROS levels. RESULTS: Gdf9 and Bmp15, Gpx1 and Sod1 were up-regulated in PCOS and control oocytes cultured in all melatonin concentrations compared to those cultured in IVM basal medium (P < 0.05). A significant decrease in the total ROS level was observed in all groups cultured in the supplemented cultures. Melatonin increased Bcl2 and decreased Bax gene expression in PCOS and control oocytes compared to non-treated oocytes. CONCLUSIONS: Melatonin increased antioxidant gene expression and regulated the apoptosis pathway, effectively reducing the adverse effects of culture conditions on PCOS oocytes. Furthermore, it influenced the expression of oocyte maturation-related genes in PCOS, providing valuable support during the IVM process.

Differential expression of innate/adaptive immunity genes induced by endometrial scratching as a hopeful approach for implantation boosting in unexplained, repeated implantation failure: An RCT.

BACKGROUND: Endometrial scratching (ES) has been proposed as a potential treatment for implantation improvement in unexplained repeated implantation failure (uRIF) patients, however, little is known about its exact molecular mechanisms. OBJECTIVE: This randomized controlled trial (RCT) was conducted on twenty uRIF patients to investigate the expression of innate and adaptive immune signaling genes after ES. METHODS: Ten uRIF patients in the intervention (twice endometrial sampling in follicular and luteal phases) and 10 uRIF patients in the control group (only luteal phase sampling) were randomly enrolled. Gene expression analysis with innate and adaptive immune response PCR-array kit between intervention and control groups were performed. RESULTS: Among innate immune-associated genes, a significant decrease was observed in the expression of APCS, CPR, CCL2, NLRP3, HLA-A, TLR3 and TLR4 in the intervention group. In adaptive immune-related genes, the expression level of CD80, CD86, CXCR3, IFNγ, IFNα1, IFNß, MBL2, CCR6, CCR8 and IL17A were decreased and CSF2, GATA3, and IL4 increased significantly in the intervention group (P < 0.05). Of 14 uRIF patients, five live birth (35.71 %) was achieved. CONCLUSION: ES in uRIF patients may exert positive effects on the endometrial preparation which increases its receptivity for embryo implantation by modulating the expression of an array of immune signaling pathway genes.

Effect of parental depressive symptoms on offspring's brain structure and function: A systematic review of neuroimaging studies.

Perinatal Depression (PND) is a severe mental disorder that appears during pregnancy or in the post-partum. Although PND has been associated with behavioral problems in the offspring, its effects on brain development are unclear. With this review we aimed at summarizing the existing literature on the effects of perinatal depressive symptoms on children's brains. A search on PubMed and Embase of structural, functional Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) studies exploring the effect of PND on offspring's brain was conducted. We selected twenty-six studies, ten structural MRI, five DTI, six fMRI and five with combined techniques. Overall, the studies showed: a) gray matter alterations in amygdala and fronto-temporal lobes; b) microstructural alterations in amygdala, frontal lobe, cingulum, longitudinal fasciculus and fornix; and c) functional alterations between limbic and mesocortical networks. The small sample size and the heterogeneity in populations and methodologies limit this review. In conclusion, PND seems to influence structure and function of offspring, that may contribute to the risk of behavioral disturbances later in life.

Comparison of various aspects of women's lives between infertile and women with and without tubal ligation: a comparative cross-sectional study.

BACKGROUND: The aim of this study is to compare anxiety, depression, body image, self-esteem, sexual function, and quality of life (QoL) between infertile women and control fertile women undergoing tubal ligation (TL) and using condom. METHODS: This cross-sectional study was conducted on 600 women in three groups of infertile and control fertile women with or without TL (200 women in each group), who met the inclusion criteria. They were selected from Royan Institute and a number of health care centers in Tehran (Iran) from May 2017 to February 2019. The subjects were asked to fill out the Short Form Health Survey (SF-12), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), Body Image Concern Inventory (BICI), and Rosenberg' Self-Esteem Scale (RSES). One-way ANOVA was used to identify the possible statistical differences between the three groups of participants. RESULTS: The mean scores of all FSFI domains were lower in the control TL women, and the differences between the three groups in all dimensions were statistically significant. In addition, the TL group had more female sexual dysfunction (FSD) comparing to the infertile and condom group (22.43 ± 5.30, 24.79 ± 4.74, and 28.03 ± 3.29, respectively P < 0.001). There was a significant difference between the three groups in SF-12 scores (76.59 ± 13.14, 68.49 ± 14.47, and 78.87 ± 12.62, respectively P < 0.001). Also there was a significant difference between the three groups in anxiety, depression, and total scores of HADS (P < 0.001). Furthermore, infertile women had lower body image (P < 0.05) and the TL group had lower self-esteem comparing to the two other groups (P < 0.05). CONCLUSIONS: The findings revealed the adverse effects of using TL on the anxiety, depression, sexual life, body image, and QoL of women. It is recommended that health-care professionals should increase their awareness and knowledge regarding the side-effects of using TL on women's lives and share this information with the patients.

Linking Brain Biology to Intellectual Endowment: A Review on the Associations of Human Intelligence With Neuroimaging Data.

Human intelligence has always been a fascinating subject for scientists. Since the inception of Spearman's general intelligence in the early 1900s, there has been significant progress towards characterizing different aspects of intelligence and its relationship with structural and functional features of the brain. In recent years, the invention of sophisticated brain imaging devices using Diffusion-Weighted Imaging (DWI) and functional Magnetic Resonance Imaging (fMRI) has allowed researchers to test hypotheses about neural correlates of intelligence in humans.This review summarizes recent findings on the associations of human intelligence with neuroimaging data. To this end, first, we review the literature that has related brain morphometry to intelligence. Next, we elaborate on the applications of DWI and restingstate fMRI on the investigation of intelligence. Then, we provide a survey of literature that has used multimodal DWI-fMRI to shed light on intelligence. Finally, we discuss the state-of-the-art of individualized prediction of intelligence from neuroimaging data and point out future strategies. Future studies hold promising outcomes for machine learning-based predictive frameworks using neuroimaging features to estimate human intelligence.

The role of sperm in inducing genomic changes in the implantation: An experimental study.

Endometrial receptivity and implantation are important topics in reproductive sciences. No evidence was found to support sperm involvement in endometrial receptivity and its associated factors. This study aimed to explore the effect of the normal human spermatozoa-endometrium cell interaction in regulating genes in the endometrial receptivity pathway. Semen samples were collected from a healthy and fertile man; then, they were incubated with endometrial cells for 24 hr and considered as the sperm group. A group was cultured without spermatozoa and considered as a control group. About 24 hr later, cells were collected from the bottom of the culture dish. The expressions of the VEGF, FGF2, HBEGF, LIFR, EGF, LIF, MUC1, HOXA10, CSF and PGR genes were evaluated in the two groups. Statistical analysis was performed using an independent sample test. Compared with the control group, in the sperm group, the mRNA levels of PGR (p = .0451), VEGF (p = .0101), HBEGF (p = .0163), EFG (p = .0339), FGF2 (p = .012), LIF (p = .0324), LIFR (p = .0321) and HOXA10 (p = .0098) were significantly upregulated. The results showed that there is a need for the interaction between spermatozoa and endometrium for implantation and can be used for preparing uterine in in vitro fertilisation cycles.

Anti-Müllerian Hormone Predictive Levels to Determine The Likelihood of Ovarian Hyper-Response in Infertile Women with Polycystic Ovarian Morphology.

BACKGROUND: The objective of this study was to investigate serum levels of anti-Müllerian hormone (AMH) in normal-ovulatory infertile women with polycystic ovarian morphology (PCOM) and their association with ovarian hyper-response. MATERIALS AND METHODS: This prospective cohort study was carried out on 100 infertile women with PCOM who were treated with an antagonist/agonist triggered stimulation protocol at Shahid Akbar-Abadi Hospital IVF Centre, Tehran, Iran. Serum AMH levels were measured before starting the assisted reproductive technology (ART) cycle and the ovarian hyper-response was evaluated by retrieved oocyte numbers, ooestradiol levels on the triggering day, and the incidence of ovarian hyper-stimulation syndrome (OHSS) clinical signs and symptoms. Logistic regression and the area under the curve (AUC) were used to estimate the effects of AMH and the accuracy of the test. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that AMH could significantly predict ovarian hyper-response in PCOM patients (AUC=0.73). The estimated threshold value was 4.95 ng/ml, with a specificity of 74.58% (95% confidence interval [CI]: 50.85, 93.22) and sensitivity of 73.17% (95% CI: 48.78, 92.68). Logistic regression results showed a significant interaction between AMH and body mass index (BMI, P=0.008), which indicated that BMI had a moderation effect. CONCLUSION: Individualized stimulation protocols for patients with isolated PCOM and AMH greater than 4.95 ng/ml may significantly reduce the chances of developing OHSS. However, the AMH cut-off values to predict ovarian hyperresponse differ for different BMI categories among PCOM patients; thus, it becomes a more precise predictive marker with increasing BMI.

Relationship between sperm parameters and clinical outcomes of Intra Uterine Insemination (IUI).

BACKGROUND: Intrauterine insemination (IUI) is a widely utilized method for treating the infertile couples. The aim of the present study was to determine the pregnancy and abortion rates after IUI and to examine the relationship of sperm parameters with these rates. METHODS: This retrospective study was performed on 911 infertile couples undergoing IUI treatment in Shahid Akbarabadi IVF Centre from May 2017 to May 2019. To evaluate the correlation of sperm parameters with the clinical pregnancy and abortion rates, odds ratio (OR) with 95% confidence intervals (CI) was calculated. RESULTS: In this study, the pregnancy rate following IUI was 15.7% (143/911), and among women who achieved pregnancy, the abortion rate was 42.0% (60/143). According to the multiple logistic regression analysis, none of the sperm parameters was associated with the pregnancy rate. Couples with either male or female factor infertility etiologies were more likely to get pregnant than those with unexplained infertility. Regarding the abortion rate, multiple logistic regression analysis revealed that normal sperm count was related to a lower abortion rate (adjusted OR=0.25, 95% CI=0.07-0.91). CONCLUSION: The present study did not reveal a significant relationship between none of the sperm parameters and pregnancy rate after IUI treatment. However, among women who got pregnant, continuation of the pregnancy was associated with the normal sperm count. Furthermore, analysis of all semen parameters together in comparison to one parameter alone might be more accurate to predict pregnancy or abortion. Further prospective cohort studies with a large number of couples are required.

Detailed Investigation of Downstream TLR Signaling in the Follicular Cells of Women with Endometriosis.

BACKGROUND: Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses. METHODS: Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p<0.05 was considered statistically significant. RESULTS: Quantitative-PCR analysis suggested that TLR1, 5, 6, 7, 8, 10, MYD88, NF-ĸB, IL-10 and TGF-ß genes expression significantly increased in patients compared to the control group (p<0.05). TLR3, 9, INF-ß genes expression was significantly lower in endometriosis than control group (p<0.05). There was no significant difference in the expression of TLR2, TLR4, TIRAP, TRIF, TRAM, and IRF3 between two groups. Also, significant increase in the levels of IL-6, IL-8 and MIF protein in FF of endometriosis group was detected in comparison with normal women (p<0.05). CONCLUSION: The expression of TLR downstream signaling in the follicular cells can initiate inflammatory responses and changes in the FF cytokine profile which in turn may induce endometriosis and infertility disorder.

The Effect of Preincubation Time and Myo-inositol Supplementation on the Quality of Mouse MII Oocytes.

BACKGROUND: It is demonstrated that optimal preincubation time improves oocyte quality, fertilization potential and developmental rate. This study aimed to evaluate the effect of preincubation time in the simple and myo-inositol supplemented medium on the oocyte quality regarding oxidative stress and mitochondrial alteration. METHODS: Cumulus oocyte complexes (COCs) retrieved from superovulated NMRI mice were divided in groups of 0, 4 and 8 hr preincubation time in the simple and 20 mmol/L myo-inositol supplemented media. Intracellular reactive oxygen species (H2O2), glutathione (GSH), mitochondrial membrane potential (MMP), ATP content, and mitochondrial amount were measured and analyzed in experimental groups. One-way ANOVA and Kruskal-Wallis were respectively used for parametric and nonparametric variables. Statistical significance was defined as p<0.05. RESULTS: In comparison to control group, variables including ROS, GSH, mitochondrial amount, fertilization and developmental rates were significantly changed after 4 hr of preincubation in the simple medium, while MMP decreased following 8 hr of preincubation in the simple medium (p˂0.001). Preincubation of oocytes up to 8 hr in the simple medium could not decrease ATP content. For both 4 and 8 hr preincubation times, myo-inositole could decrease H2O2 and increase GSH and MMP levels and consequently could improve fertilization rate compared to oocytes preincubated in the simple culture. CONCLUSION: It seems that 4 hr or more preincubation time can decrease the oocyte quality and lead to reduced oocyte fertilization and developmental potential. Howevere, myo-inositol may prevent oocyte quality reduction and improve fertilization potential in comparision to the equivalent simple groups.

Diet and The Risk of Endometriosis in Iranian Women: A Case-Control Study.

BACKGROUND: Endometriosis is one of the most common pelvic diseases associated with dyspareunia, pelvic pain, and infertility. The primary aim of this study is to evaluate the role of diet on the risk of endometriosis among Iranian women. MATERIALS AND METHODS: This case-control study was conducted in two health research centres between 2015 and 2016. There were 207 women with endometriosis (case) and 206 women without endometriosis (control) who were evaluated by laparoscopy. The women were asked about their frequency of consumption per week of portions of selected dietary items in the Iranian diet in the year before the interview. RESULTS: The results indicated that intake of green vegetables (odds ratio [OR]=0.39, 95% confidence interval [CI]=0.21-0.74, Ptrend=0.004), red meat (OR=0.61, 95% CI=0.41-0.91, Ptrend=0.015) and dairy products (milk [OR=0.65, 95% CI=0.47-0.92, Ptrend=0.014], cheese [OR=0.53, 95% CI=0.37-0.76, Ptrend<0.001]), fresh fruit (OR=0.68, 95% CI=0.50-0.93, Ptrend=0.015) and grain legumes (OR=0.59, 95% CI=0.47-0.77; Ptrend<0.001) had a significant association with lower risk of endometriosis. Consumption of carrots, green tea, fish, eggs and oil was not significantly related to the risk of endometriosis. CONCLUSION: This study suggests that certain types of dietary components may be related to the risk of endometriosis.

Proteome analysis of endometrial tissue from patients with PCOS reveals proteins predicted to impact the disease.

Polycystic ovary syndrome (PCOS) is a complex disease that causes an ovulatory infertility in approximately 10% of reproductive-age women. We searched for candidate proteins that might contribute to endometrial receptivity defects in PCOS patients, and result in adverse reproductive outcomes. Shotgun proteomics approach was used to investigate the proteome profile of the endometrium at the luteal phase in PCOS patients compared to healthy fertile individuals. Biological process and pathway analyses were conducted to categorize the proteins with differential expressions. Confirmation was performed for a number of proteins via immunoblotting in new samples. 150 proteins with higher abundance, and 46 proteins with lower abundance were identified in the endometrial tissue from PCOS patients compared to healthy fertile individuals. The proteins with higher abundance were enriched in protein degradation, cell cycle, and signaling cascades. Proteins with lower abundance in PCOS patients were enriched in extracellular matrix (ECM) composition and function, as well as the salvage pathway of purine biosynthesis. Metabolism was the most affected biological process with over 100 up-regulated, and approximately 30 down-regulated proteins. Our results indicate significant imbalances in metabolism, proteasome, cell cycle, ECM related proteins, and signaling cascades in endometrial tissue of PCOS, which may contribute to poor reproductive outcomes in these patients. We postulate that the endometria in PCOS patients may not be well-differentiated and synchronized for implantation. Possible roles of the above-mentioned pathways that underlie implantation failure in PCOS will be discussed. Our findings need to be confirmed in larger populations.

Restoration of estrous cycles by co-transplantation of mouse ovarian tissue with MSCs.

This study investigates the effect of bone marrow (BM-MSCs) and visceral peritoneum (VP-MSCs)-derived mesenchymal stem cells on the transplanted ovary. VP-MSCs and BM-MSCs were obtained from green fluorescent protein-expressing mice (GFP+). Six- to eight-week-old female NMRI mice were divided into four experimental groups, autograft ovarian tissue fragments (AO), autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel (AO-H), autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel containing BM-MSCs (AO-HB) and autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel containing VP-MSCs (AO-HP). Intact ovary (IO) was the control group. The estrous cycles resumption time was monitored and at the third estrous cycle, the blood samples and grafted ovaries were evaluated using hormonal, histological and gene expression analysis. Onset of estrous cycles, especially at the second cycle, was earlier in AO-HB and AO-HP groups than in the AO-H group (P < 0.05). Moreover, E2 and FSH levels in AO-HB and AO-HP groups were returned to those of the intact group. However, folliculogenesis was still retarded as compared with the IO group. The gene expression of theca (Lhcgr, Cyp17a1, Gli2, Gli3 and Ptch1), granulosa (Amh and Fshr), oocyte (Zp3 and Gdf9), germ cells (Stella and Prdm1), angiogenesis (VEGF and bFGF) and apoptosis (Bax/Bcl2 and Caspase3) markers was similar in both AO-HB and AO-HP groups. Expression of Amh, Fshr, Gdf9 and VEGF increased only in the AO-HP group whereas expression of Ptch1 increased only in the AO-HB group, as compared with the AO group (P < 0.05). In conclusion, BM-MSCs or VP-MSCs can improve ovarian autotransplantation in mice with no superiority over each other.