فهرست مطالب fatemehsadat amjadi

A significant association between endometrial vascularity and pregnancy has been shown in previous research, while poor vascularization was attributed to repeated implantation failure (RIF). One possible approach to enhance angiogenesis for successful implantation is endometrial scratching (ES).

The purpose was to investigate endometrial responses to scratching by profiling angiogenesis-related gene expression in unexplained RIF participants.

In this randomized controlled trial study, 20 infertile women with unexplained RIF were assigned to 2 groups by the balanced block randomization method (n = 10/each group): the intervention group (group A) (who received ES in the follicular phase) and the control group (group B). Endometrial biopsy was performed in the secretory phase. Gene expression profiling was performed using a polymerase chain reaction-array kit for human-angiogenic growth factors. The implantation and clinical pregnancy rates were also assessed.

Among the angiogenesis-promoting genes, FGF1, FGF13, FGF2, TGFA, ANG, ANGPT1, and VEGFA were significantly upregulated (p < 0.05). IL12A (an angiogenesis-inhibiting cytokine) was significantly upregulated (p < 0.01). In contrast, 15 genes with angiogenesis-related functions, including CXCL11, CXCL13, CXCL3, CXCL5, CXCL6, EREG, FIGF, FST, IL10, LEP, PPBP, PROK1, RHOB, TNF, and TYMP, were downregulated after ES. No significant differences were observed between the intervention (group A) and control (group B) groups in terms of implantation (43.75% vs. 28.57%) or clinical pregnancy rates (75% vs. 57.1%).

ES induced significant alterations in the expression of angiogenesis-related genes, with notable up/downregulation of key angiogenic/antiangiogenic factors. These findings enhance our understanding of the molecular responses triggered by ES, underscoring the potential influence of ES on the complex processes of angiogenesis crucial for implantation.

 Seminal plasma exosomes are now recognized to play a complex role in the regulation of the female reproductive system infertility. The objective of this study was to assess the effect of exosomes derived from the sperm of men with oligoasthenoteratozoospermia on endometrial implantation-related genes.

To isolate the exosomes, we employed an ultracentrifugation method on samples derived from 10 fertile men with normal sperm parameters and 10 men with oligoasthenoteratozoospermia. The size distribution and ultrastructure of the exosomes were then characterized using transmission electron microscopy and dynamic light scattering. We detected an exosome marker using western blot analysis and confirmed the cytoplasmic localization of the exosomes by incubating them with DiI dye and visualizing them using fluorescence microscopy. After 6 hours of in vitro treatment of endometrial epithelial cells with 100 µg/ml seminal exosome, the endometrial receptivity genes were examined using qRT-PCR. To perform data analysis and quantification, we utilized Image J and Prism software. P< 0.05 were considered statistically significant.

After 6 hours of treatment, the mRNA levels of MUC1, LIF, G-CSF, CX3CL1, and VEGF were significantly downregulated in the endometrial epithelial cells treated with oligoasthenoteratozoospermia exosomes compared to the normal group. Although changes were observed in the mean mRNA levels of IL8 and TGF-ß genes in the oligoasthenoteratozoospermia group compared to the normal group, these differences did not reach statistical significance (p > 0.05).

Oligoasthenoteratozoospermia exosomes have a distinct effect on endometrial receptivity compared to normal exosomes, leading to reduced expression of implantation-related genes.

Ectopic pregnancy (EP) is defined as embryo implantation in a location other than the uterine cavity.

We aimed to evaluate the expression of several genes, which may play a role in EP, in the ampulla region of fallopian tubes and endometrial tissue of women with EP.

In this case-control study, 5 women who underwent salpingectomy due to EP, comprised the 5 pseudo-pregnant women as a control group. These participants referred to the Royan Institute, and Shariati, and Arash hospital, Tehran, Iran during 2019-2021. We evaluated the expressions of vascular endothelial growth factor A, mucin-1, colony-stimulating factor-1, heparin-binding epidermal growth factor-like growth factor (HBEGF), and fibroblast growth factor 2 genes in the fallopian tube and endometrium of EP cases by real-time polymerase chain reaction using specific primers.

The vascular endothelial growth factor expression was significantly higher in the ampulla region of the controls. However, no significant differences were observed in endometrial tissue. Assessments of colony-stimulating factor-1 and fibroblast growth factor 2 showed no significant differences between the case and control groups. HBEGF showed significantly higher expression in the ampulla region of EP cases, but no significant difference was observed in HBEGF expression in the endometrial tissues of the study groups. Mucin-1 expression was significantly higher in both study regions of the EP cases.

Our results have strongly suggested that these genes play important roles in proper implantation, and disruptions in their expression patterns could lead to EP. However, more studies are needed to confirm the current findings.

Toll-like receptors (TLRs) located in the fallopian tube epithelial cells play a crucial role in the immunological response to sperm and pathogens. The present study aimed to compare the function and response of TLR3, TLR4, and TLR5 receptors in the presence of sperm under both physiological and pathological conditions in vitro.

In this descriptive laboratory study, OE-E6/E7 cells were cultured with fresh sperm samples obtained from normozoospermic individuals (n=10) and specific ligands for TLR3, TLR4, and TLR5 receptors in three groups consisting of sperm, specific ligands, and sperm + specific ligands. A control group was also included without adding sperm or ligand. The concentrations of IL-6 and IL-8 secreted from OE-E6/E7 cells in all four groups were determined using the ELISA method.

Exposure of sperm and specific ligands to TLR3, TLR4, and TLR5 receptors in fallopian tube epithelial cells led to a significant increase in the concentration of IL-6 and IL-8 cytokines. There was no significant difference in the secretion of these cytokines from OE-E6/E7 cells between the two groups of ligand and ligand + sperm.

The response of fallopian tube epithelial cells to sperm exposure through TLRs leads to an increase in cytokine secretion. However, simultaneous exposure of sperm and TLR-specific ligands does not result in a cumulative increase in cytokine secretion. Therefore, it is plausible that the TLR signaling pathway may be regulated negatively by some other factors. Further studies are required to investigate this issue.

Hormonal imbalance is one of the important etiological factors for Oligoasthenoteratospermias (OAT).

This study aimed to evaluate the effects of hormonal changes including prolactin, TSH, testosterone, luteinizing hormone, follicle-stimulating hormone and anti-Mullerian hormone on sperm DNA fragmentation in normal men compared with OAT to design a clinical algorithm for the comprehensive study of male factor infertilities.

We consecutively selected 60 candidates referred to the infertility clinic to collect the semen and blood samples. Then, a terminal deoxynucleotidyl transferase dUTP nick end labeling test was performed to evaluate the sperm DNA fragmentation index (DFI). After semen analysis and DFI checking, they were classified into 4 groups consisting of normospermia and OAT men each with or without increased DFI. Hormone parameters were analyzed using enzyme-linked immunoassay.

Follicle-stimulating hormone and luteinizing hormone levels showed positive correlations with DFI in a significant way (p ≤ 0.01), while testosterone and thyroid-stimulating hormone were associated with sperm concentration. Prolactin and anti-Mullerian hormone levels significantly correlated (p ≤ 0.01) with sperm concentration and DFI value simultaneously.

Decreased and increased levels of serum hormones could adversely affect semen profile and sperm DNA integrity which lead to severe male infertility. Although we investigated the effects of the main hormones related to male infertility on DNA damage, the role of these hormones on the fertilization rate and embryo quality needs to be evaluated in further studies.

Context:

 The SARS-CoV-2 virus causes dysfunction of vital organs in the body. Concerns about the destructive effect of SARS-CoV-2 on human reproductive tissues and fertility have increased. Evaluation of the possible mechanisms by which SARS-CoV-2 causes infertility is essential for effective prevention and treatment. This review aims to assess the studies that have been conducted on SARS-CoV-2 impacts on the human reproductive system.

Evidence Acquisition:

 This review study investigated articles indexed in PubMed, Science-Direct, Scopus, and google scholar databases from 2019 to 2021. The Keywords SARS-CoV-2, COVID-19, human reproductive system, testis, and ovary were searched in the mentioned databases.

 The present study assessed the expression of SARS-CoV-2-specific receptors, the presence of the virus in the human reproductive system, and the mechanisms by which this virus can affect human fertility.

 SARS-CoV-2, like other viruses, may indirectly influence the male reproductive system through cytokine storms, inflammation-causing oxidative stress, and its possible complications. The direct effects of SARS-CoV-2 on the male reproductive system are also reported. The testis may be a potential target for the SARS-CoV-2 virus. The impact of the SARS-CoV-2 virus on women's reproductive performance is unknown and requires further investigation.

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.

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.

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).

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.

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.

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.

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.

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.

Many researchers consider implantation and endometrial receptivity as pertinent issues in reproductive science by. Although, several experiments have been performed and their results evaluated, yet there is no confirmed evidence about the related factors and the role of sperm in endometrial receptivity.

To investigate the effect of the sperm-endometrium interaction in regulating genes involved in the endometrial receptivity pathway.

In this experimental study, 10 male and 30 female NMRI mice were included, and half of the male cases were vasectomized. The subjects were divided into two groups as follows; group 1 (case) comprised of 15 females mated with 5 non-vasectomized male mice, while group 2 (control) consisted of 15 females mated with 5 vasectomized males. Cases were sacrificed and assessed after 36 hr and the endometrial tissue was extracted and kept at -80ºC until the next use. The expression of the endometrial receptivity pathway genes, including VEGF, HBEGF, FGF2, EGF, LIF, LIFR, HOXA10, MUC1, PGR, and CSF, was examined in both groups. For statistical analysis, an independent samples test (Mean ± SD) was used.

The mRNA levels of LIF (p = 0.045), LIFR (p = 0.040), MUC1 (p = 0.032), VEGF (p = 0.022), EFG (p = 0.035), and FGF2 (p = 0.040) were significantly upregulated in the case group compared with the control group.

Finally, seminal plasma was observed to be effective in expressing the involved genes in the successful implantation pathway, including LIF, LIFR, MUC1, VEGF, EGF, and FGF2.

Follicular fluid (FF) plays a key role in preparing a microenvironment for the development and fertilization of oocytes. Moreover, biochemical and hormonal changes in the FF surrounding the oocyte can affect its quality and successful fertilization. The present study was conducted to investigate the relationship of beta human chorionic gonadotropin (beta-HCG) and anti-mullerian hormone (AMH) levels of FF with oocyte maturation in in-vitro fertilization (IVF) cycles.

FF was monitored in 30 women under a controlled ovarian stimulation cycle. Oocyte maturation was examined by an embryologist. Beta-HCG and AMH levels were then investigated in the FF containing metaphase I (MI), metaphase II (MII) and germinal vesicle (GV) oocytes using ELISA. To evaluate clinical pregnancy, serum levels of beta-HCG were measured 14 days after transfering the embryo. Identifying fetal heart rate (FHR) was considered clinical pregnancy.

No significant differences were observed in the mean betal-HCG levels between the mature (53.73±21.081 IU/ml) and immature oocytes (52.90±21.000 IU/ml) (P=0.8). Beta-HCG levels of the FF containing the MII oocytes (64.73±14.49 IU/ml) were significantly related to clinical pregnancy (P=0.04). Oocyte maturation and clinical pregnancy were also found not to be significantly related to AMH levels of FF.

The present study found oocyte maturation not to be significantly associated with the beta-HCG and AMH levels of FF. Beta-HCG levels of FF were also found to be associated with clinical pregnancy. The other constituents of FF along with AMH and beta-HCG might have therefore affected the oocyte quality and maturation.

In about 40% of the couples, the cause of infertility problems is attributed to men because of low sperm production and disturbed motility of sperm. Pieces of evidence show that Myo-inositol has a potential role for the treatment of sperm morphology and male fertility.

This study aimed to determine the effect of Myo-inositol on the sperm parameters and fertility rate in patients with oligoasthenospermia treated by intrauterine insemination (IUI).

This study was a randomized clinical trial conducted on 37 patients with oligoasthenospermia treated by IUI during 2016-2017. In this study, the patients were randomly divided into two groups of oligoasthenospermia treated with (Case group) and without Myo-inositol (Control group). The case group received 0.5 ml of Myo-inositol with a concentration of 2 mg/ml and incubated at 37ºC incubator for 2 hr, but the control group had no interventions.

The results of this study showed that although there was no significant difference in sperm parameters including sperm motility and concentration before processing with Myo-inositol in the case group, but there was a significant increase in sperm motility during the treatment with Myo-inositol. The therapeutic effect of this method was confirmed on induction of pregnancy in 18% of the treated patients, in such a way that was about twice greater than those who did not receive the drug.

According to the results of this study, the use of Myo-inositol is efficient enough to change sperm parameters to increase the chance of fertility.

NOTCH signaling pathway is well known for its role in cell fate, cell survival, cell differentiation, and apoptosis. Some of the NOTCH signaling genes are critical for endometrial function and implantation in animals and appear to play a similar role in humans. The purpose of the current study was to investigate the potential roles of some main components of the NOTCH family in human endometrium during implantation period in common gynecological diseases. Endometrial NOTCH receptors NOTCH1, 3, 4 and ligand JAG1, 2 and survivin mRNA expression were investigated using the Q-PCR technique and the amount of the JAG1, 2 proteins was also determined by Western blot. Samples were obtained from 12 patients with endometriosis, 12 patients with repeated implantation failure (RIF), 12 patients with Polycystic Ovary Syndrome (PCOS) and 10 healthy fertile women as a control group. Data were analyzed using SPSS version 18. Group comparisons were performed by one-way ANOVA or Kruskal-Wallis. All patient groups failed to show the expected mid-luteal increase in NOTCH1, JAG 1, 2, and survivin expression as documented in the control group. Moreover, a significant rise in NOTCH3 expression levels was found only in PCOS women. There was a direct correlation between gene expression and protein level for JAG 1, 2. Aberrant NOTCH signaling molecules expression suggests that altered development of the endometrium at the molecular level may be associated with the impaired decidualization and implantation failure in gynecological disorders such as endometriosis, PCOS, and RIF.

Prenatal drug exposure, as a common public health concern, is associated with an increased risk of adverse effects on early embryo development.

To investigate the in vitro development of - embryo from experimentally Kerack-addicted mice.

Twenty-five female mice were studied in five groups: control, vehicle, and three experimental groups of Kerack-dependent mice (I, II, and III) which received different doses of Kerack for 14 days. After the establishment of addiction model (7 days), experimental groups I, II, and III were given Kerack intraperitoneally at the doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively. The vehicle group received normal saline and lemon juice whilst the control group just received water and food. Morulae were obtained through oviduct flashing. The survived embryos were cultured in T6 5mg/ml bovine serum albumin. The developmental rates up to hatched stage daily and embryo quality (differential staining and Tunnel staining) were also assessed.

The developmental potential of embryos obtained from the addicted mother was significantly decreased in comparison with control group. There was a significant reduction in the rate of blastocyst formation in the high dose Kerack dependent group. However, in addicted mice there was reduction in the total cell number (40.92% vs. 65.08% in control) and, inner cell mass percentage (17.17% vs. 26.15% in control) while apoptotic cells numbers were increased (7.17 vs. 1.46 in control) (p

The Kerack addiction during pregnancy retards preimplantation development and induces apoptosis.

Tumor development is angiogenesis dependent. There is evidence that leptin contributes to tumor growth. However, all the mechanisms by which leptin does this has not been clearly established. The objective of the present study was to test the hypothesis that leptin enhances melanoma tumor growth through inducing angiogenesis and cell proliferation.

We injected 2 × 106 B16F10 melanoma cells subcutaneously to 32 C57BL6 mice. The mice were randomly divided into four groups of eight animals, on day 8. Two groups received twice daily intraperitoneal (i.p.) injections of either phosphate buffered saline or recombinant murine leptin (1 μg/g initial body weight). Two groups received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/injection every 3 consecutive days. By the end of the 2nd week, the animals were euthanized and blood samples and tumors were analyzed. Angiogenesis and proliferation were assessed by immunohistochemical staining for CD31 and Ki-67 respectively.

Tumors size, capillary density, plasma levels of vascular endothelial growth factor, and the number of Ki-67-positive stained cells were significantly more in the leptin than 9F8 and both control groups (P < 0.05).

Taken together, our findings reinforce the idea that leptin acts as an angiogenic and mitogenic factor to promote melanoma growth

Toll like receptors (TLRs) are one of the main components of the innate immune system. It has been reported that expression of these receptors are altered in the female reproductive tract (FRT) during menstrual cycle. Here we used a fallopian tube epithelial cell line (OE-E6/E7) to evaluate the effect of two sex hormones in modulating TLR expression. In this experimental study, initially TLR gene expression in OEE6/ E7 cells was evaluated and compared with that of fallopian tube tissue using quantitative real time-polymerase chain reaction (qRT-PCR) and immunostaining. Thereafter, OE-E6/E7 cells were cultured with different concentrations of estradiol and progesterone, and combination of both. qRT-PCR was performed to reveal any changes in expression of TLR genes as a result of hormonal treatment. TLR1-10 genes were expressed in human fallopian tube tissue. TLR1-6 genes and their respective proteins were expressed in the OE-E6/E7 cell line. Although estradiol and progesterone separately had no significant effect on TLR expression, their combined treatment altered the expression of TLRs in this cell line. Also, the pattern of TLR expression in preovulation (P), mensturation (M) and window of implantation (W) were the same for all TLRs with no significant differences between P, M and W groups. These data show the significant involvement of the combination of estradiol and progesterone in modulation of TLR gene expression in this human fallopian tube cell line. Further experiments may reveal the regulatory mechanism and signalling pathway behind the effect of sex hormones in modulating TLRs in the human FRT.

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. 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. 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 signifi cantly higher than in the luteal phase (P value < 0.05). It seems that diff erentially expressed apolipoprotein A1 negatively aff ects endometrial receptivity in patients with polycystic ovary syndrome. The results showed that apolipoprotein A1 level signifi cantly 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.

The human female reproductive tract (FRT) is constantly deal with the invading pathogens. Recognition of these pathogens is attributed to the family of Toll like receptors (TLR) as a major part of the innate immune system. We and others have previously revealed that TLRs1-6 express in the female reproductive tract. However, more studies should be done to detect TLRs 7-10 in the female reproductive tract, especially in the fallopian tubes.

To examine the expression of TLRs7-10 in human fallopian tube tissue.

Using immunostaining techniques, distribution of TLR7-10 was studied in surgical sections from the uterine tubes, obtained from patients undergoing tubal ligation and hysterectomy for benign gynecological conditions. RT-PCR was used to show the existence of TLR7-10 genes in fallopian tube tissue.

TLR7-10 proteins were detected in the fallopian tube epithelium, although the intensity of staining was not equal in cases. TLR7-10 genes were expressed in human fallopian tube tissue.

This study indicates that TLR7-10 is expressed in fallopian tubes tissues, and may play an important role in microbial recognition, and in host defense against ascending infection.

Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Leptin is a peptide predominantly produced by adipocytes. Obesity increases the expression of leptin. On the other hand, several recent experiments have suggested that tumor growth to be dependent on endothelial progenitor cells (EPCs) which are effective in generation of new blood vessels. Our objectives in the present study were to examine the effects of leptin on melanoma growth and circulating EPCs number. Melanoma tumors were induced by subcutaneous injections of 2 × 106 B16F10 melanoma cells to 32 C57BL6 mice. The mice were randomly divided into 4 groups of 8 on the 8th day. The first two groups received intraperitoneal (IP) injections of either phosphate-buffered saline (PBS) or recombinant murine leptin (1 μg/g initial body weight) twice daily. The other two groups received IP injections of either 9F8 (an anti leptin receptor antibody) or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week, the animals were euthanized and blood samples were saved for computation with flow cytometry. The tumors were also analyzed. The EPC numbers in leptin, PBS, 9F8, and IgG groups were 222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26 per ml of blood, respectively. Moreover, the corresponding values for tumor weights were 3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2, 1.7 ± 0.3 g. Tumors weight and size, and circulating EPC numbers were significantly more in the leptin group than 9F8 and both control groups (P < 0.05). In conclusion, our observations indicated that leptin caused melanoma growth likely through increased circulating EPC numbers and consequently vasculogenesis.