Unexplained recurrent spontaneous abortion (RSA) might be caused by the mother's immunological rejection of the fetus. In this cross-sectional study, the percentage of T helper 17 (Th17), T regulatory (Treg) cells and their cytokines as the main players of immunomodulation in peripheral blood lymphocytes during the luteal phase of 20 women with unexplained RSA were compared with 20 normal non-pregnant women. The percentage of Treg cells in the former was significantly lower compared with controls. The percentage of Th17 cells in the former was higher than controls. Expression of IL-23, IL-17, IL-6 cytokines in the former was significantly higher than controls, but the higher expression of IL-21 was not significant. The gene expression of TGF-β and FoxP3 in the former was lower than controls. Significant positive correlations were found between the percentage of Th17 cells with IL-23, IL-6 and IL-17 and between expression of IL-23 and IL-6 and IL-17. IL-6 gene expression showed a significant positive correlation with IL-17. Therefore, imbalance of Th17-Treg cells and the consequent changes in cytokine expression might be implicated in the pathogenesis of unexplained RSA and may provide new insight into the immunoregulatory events at the maternal-fetal interface.

We intraperitoneally injected 28 adult male Sprague-Dawley rats (200-250 g) with either 0, 10 mg/kg of MDMA, or 10 mg/kg of MDMA plus 100 mg/kg of NAC. Spatial memory was assessed with a Morris Water Maze (MWM). At the end of the study, rats' brains were removed to study the structure and ultrastructure of CA1, and measure Bcl-2 and Bax expressions in the hippocampus. In the MWM, NAC treatment significantly attenuated the MDMA-induced increase in distance traveled (p < 0.05) and escape latency (p < 0.001). The decreased time spent in the target quadrant in MDMA-treated animals was attenuated by NAC (p < 0.01). NAC significantly protected against MDMA-induced apoptosis and the up- and down-regulation of Bax and Bcl-2, respectively. These data have suggested that NAC could protect against behavioral changes and apoptosis in the hippocampus following administration of MDMA. NAC might be useful for the treatment of neurotoxicity in MDMA users.

Expression of CTLA-4 and GITR were significantly down-regulated in the URSAs compared to NNPs at the window of implantation, which shows the essential role of Treg cells in creating an immunological privileged site for fetus as an allograft at the maternal-fetal interface by high expression levels of CTLA-4 and GITR during a normal pregnancy.

Curcumin, the polyphenolic compound obtained from turmeric, has several pharmacological properties. These properties include antioxidant, antimicrobial, anti-angiogenic, anticarcinogenic, antiinflammatory, and immunomodulatory activities.Therefore, the clinical efficacy of this substance has been largely investigated for curing numerous disorders. Based on a growing body of literature, this review aimed to investigate curcumin's molecular and clinical effects on reproduction and related disorders. Curcumin in the female reproductive system attenuates folliculogenesis, promotes apoptosis of oocytes and blastocyst, and decreases embryo implantation and survival. Curcumin at <100 mg concentration shows protective effects against testicular injury. The concentration of >250 mg of curcumin exhibits immobilizing action on sperms, and at 500 mg concentration completely blocks pregnancy. Curcumin inhibits vaginal infections, attenuates the severity of the premenstrual syndrome, ameliorates inflammatory conditions in polycystic ovary syndrome, improves preeclampsia, and prevents ectopic endometrial lesions. Taken together, curcumin, because of the numerous biological activities, low level of toxicity, and lower adverse effects compared to the synthetic drugs, could be considered as a protective agent for preserving the semen quality parameters, a contraceptive, and chemotherapeutic or chemopreventive agent, as well as an appropriate agent for the treatment of female reproductive disorders.

Background: Endometriosis is associated with abnormal immunologic responses and combined inflammatory and anti-inflammatory conditions. Objective: This study aims to investigate follicular fluid (FF) concentration of interleukin (IL)-3, IL-5, and IL-6 in women with and without endometriosis. Materials and Methods: In this cross-sectional study 68 women who were referred to the in vitro fertilization center of Imam Reza hospital in Mashhad during 2018 were selected randomly. Leaves of cytokines in the FF samples were evaluated in the endometriosis and the control group (n = 34/each). The diagnostic accuracy of cytokines and clinical characteristics were evaluated. Results: IL-3 and IL-6 were significantly changed in the FF of the women with endometriosis compared with the control group (p = 0.04, and p < 0.01, respectively), and the mean concentration of IL-5 in the endometriosis group was lower than in the control group (p = 0.5), but this was not significant. There were significant differences in the menstrual cycle, dyspareunia, and dysmenorrhea between the groups (p < 0.01, p = 0.04, and p = 0.02, respectively). The diagnostic accuracy of IL-3 and IL-6 in the FF was low, with the area under the curve of 0.614 and 0.645, respectively. Conclusion: Although none of the cytokines had a predictive value for endometriosis, the decreased levels of IL-3 and increased levels of IL-6 in the FF samples of women with endometriosis, and risk factors, including irregular menstrual cycle, dyspareunia, and dysmenorrhea, could be associated with the pathogenesis of this painful disease. Key words: Interleukin-3, Interleukin-5, Interleukin-6, Follicular fluid, Endometriosis.

Background:Women with polycystic ovary syndrome have lower pregnancy rates, possibly due to the decreased uterine receptivity. Successful implantation depends on protein networks that are essential for cross-talk between the embryo and endometrium. Apolipoprotein A1 has been proposed as a putative anti-implantation factor. In this study, we evaluated apolipoprotein A1 expression in human endometrial tissues.Materials and Methods:Endometrial apolipoprotein A1 messenger RNA (mRNA) and protein expression were investigated using quantitative real-time polymerase chain reaction (PCR) and Western blot. The distribution of apolipoprotein A1 was also detected by immunostaining. Samples were obtained from 10 patients with polycystic ovary syndrome and 15 healthy fertile women in the proliferative (on day 2 or day 3 before ovulation, n = 7) and secretory (on days 3-5 after ovulation, n = 8) phases.Results:Endometrial apolipoprotein A1 expression was upregulated in patients with polycystic ovary syndrome compared to normal subjects. However, apolipoprotein A1 expression in the proliferative phase was significantly higher than in the luteal phase (P value < 0.05).Conclusion:It seems that differentially expressed apolipoprotein A1 negatively affects endometrial receptivity in patients with polycystic ovary syndrome. The results showed that apolipoprotein A1 level significantly changes in the human endometrium during the menstrual cycle with minimum expression in the secretory phase, coincident with the receptive phase (window of implantation). Further studies are required to clarify the clinical application of this protein.

IntroductionPolycystic ovary syndrome (PCOS) is a multifaceted syndrome correlated to hyperandrogenism and increased renin-angiotensin system activity (1,2). In other words, PCOS is a heterogeneous disease which results from interactions between genetic, epigenetic, and lifestyle factors (1). This complex endocrine disease can be observed in 5-10% of women who are in their reproductive age throughout the world (1,2).Hyperandrogenism, polycystic ovaries, and chronic anovulation based on Rotterdam criteria are the major diagnostic criteria of PCOS women (3). Further, these patients usually suffer from obesity, insulin resistance, metabolic syndrome, and cardiovascular diseases (4).Recent research recognized PCOS as a chronic lowgrade pro-inflammatory disorder associated with different metabolic and reproductive abnormalities (5). Many circulating inflammatory markers are found to mediate PCOS in response to a stimulus, including pro-inflammatory cytokines and chemokines, as well as different endothelial inflammation markers and oxidative stress and chronic inflammation markers (6).Cytokines involve in the regulation of ovarian function through controlling paracrine or autocrine ovarian processes (7). Furthermore, they control folliculogenesis and ovulation through providing an environment which supports follicle selection and growth. Regarding the folliculogenesis, cytokines regulate the proliferation or differentiation of cells, the survival or atresia of follicles, and oocyte maturation (8). Moreover, an impaired balance between cytokines with inflammatory and anti-inflammatory activities seems to involve in the development of PCOS (9).T helper cell type 2 (Th2) cytokines such as interleukin (IL-3) and IL-5 contribute to inflammatory reactions and immune responses. Additionally, IL-3 secreted from helper lymphocytes, eosinophils, and natural lethal cells affects blood progesterone and mast cells (10,11).Similarly, IL-3 concentration enhances before delivery during normal pregnancy and progesterone regulates the production of this cytokine via the induction of a specific protein designated as a progesterone-induced blocking factor (12).Likewise, IL-3 and IL-5 regulate the growth, differentiation, and activation of eosinophils under normal physiological conditions. Previous research indicated that the overexpression of IL-5 in the transgenic mice is associated with the increased number of eosinophils in Abstract Objectives: Cytokines regulate ovarian activity through controlling internal ovarian processes as paracrine or autocrine regulators. In the current study, the follicular fluid (FF) concentration of some cytokines including interleukin (IL-3), IL-5, and IL-6 were investigated and compared between 39 patients diagnosed with polycystic ovary syndrome (PCOS) and 34 healthy normal women with male factor infertility as the control group. Materials and Methods: To this end, FF samples were collected by following gonadotropin-releasing hormone antagonist protocol. Then, the FF concentration of the studied cytokines...

Objective: Vitamin D deficiency has been shown to be associated with pregnancy complications due to the effect on implantation. However, the effect of vitamin D on the clinical outcomes of IVF in women with recurrent implantation failure is unclear. Present study aimed to investigate the effect of vitamin D status in recurrent implantation failure (RIF) patients undergoing in vitro fertilization (IVF) cycles. Methods: A cross-sectional study was carried out on 52 women with RIF undergoing IVF treatments from 2018 to 2019. Blood samples were collected from participant after 2 weeks of embryo transfer and then serum 25-OH vitamin D levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Clinical pregnancy and patients’ characteristics were evaluated. Results: The incidence of vitamin D deficiency, insufficiency and sufficiency among the studied population were 7.7%, 73.1% and 19.2%, respectively. Vitamin D levels were significantly associated with clinical pregnancy in patients with ≥30 years old, being overweight, duration of marriage and infertility duration ≥5 years and having history of abortion. By adjusting confounding factors in the multivariate analysis, we found a significant association between vitamin D levels and clinical pregnancy in RIF patients (p=0.007). Conclusion: There is a significant correlation between vitamin D levels and clinical pregnancy rate in RIF woman undergoing IVF. However, more randomized, controlled trials are suggested.