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The 24th and 19th International Congresses on Reproduction and Stem Cell Biology in the Islamic Republic of Iran brought together experts and researchers worldwide to explore the latest advancements in these fields. Different topics were discussed, including such as reproductive health, infertility treatments, stem cell research, and regenerative medicine. This report provides a summary of the congress's key findings by emphasizing pioneer research and technologies that can influence the future of reproduction and stem cell biology programs. The presence of keynote speakers such as Professor Nicolas Rivron, Mohammad Ebrahim Parsanezhad, Ashraf Moini, Abbas Aflatoonian, Hadi Shafiee, Anna Brini, Omid Camron Farokhzad, and Jeffrey Schweitzer added value to the event, which had over 1100 participants from around the world. While foreign speakers were from various countries Iranian speakers mainly came from Tabriz, Isfahan, Shiraz, Babol, and Tehran that all discussed cutting-edge science and successful disease treatments. To ensure a more comprehensive representation, it is suggested that a wider geographic distribution of national and foreign speakers should be considered in future plan.
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OBJECTIVE: Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblastic invasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Altered placental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this process while the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placenta and uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expression pattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE. MATERIALS AND METHODS: In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternal blood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparison with the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32 weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14 or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR) was done to determine the expression levels of TIMP1, 2, 3 and 4 genes. RESULTS: Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic women in comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPs expression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the second control group. CONCLUSION: An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vascular defect and may be used as a determinant of complicated pregnancies with severe preeclampsia.
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OBJECTIVE: To examine the association between apolipoprotein E (APOE) gene polymorphisms and incidence of recurrent implantation failure (RIF). METHODS: In a case-control study, 100 women with RIF were compared with 100 women with at least one live child. DNA was extracted from the peripheral blood and APOE genotyping was performed through polymerase chain reaction, followed by restriction fragment length polymorphism. Statistical analysis was performed using Pearson's χ2 test. RESULTS: Our data revealed a significantly higher frequency for the E3/E4 genotype and E4 allele in the RIF group compared with controls. Significant differences in frequencies of the E4 allele (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.131-4.185; P = 0.026) and E3/E4 genotype (OR 2.203; 95% CI 1.092-4.443; P = 0.038) were observed between the groups. CONCLUSION: The E4 polymorphism is correlated with RIF occurrence in women undergoing assisted reproductive treatment and potentially can be considered as a risk factor to the human implantation process.
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Apolipoproteínas E/genética , Polimorfismo Genético , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Fatores de RiscoRESUMO
Identifying causal genes of spermatogenic failure on the male-specific region of Y chromosome (MSY) has been a challenging process. Due to the nonrecombining nature of MSY, haplotype-based approaches have recently been shown to be promising in identifying associated MSY haplogroups. We conducted an MSY analysis of nonobstructive azoospermia (NOA) patients in a case-control setting (N = 278 and 105 respectively) to identify modal haplogroups strongly associated with NOA. Patients with AZF deletions (AZF+) and no AZF deletions (AZF-) were compared with the control group. Given the larger sample set of AZF- NOA patients, we further investigated the association based on histopathological severity, namely Sertoli cell-only syndrome and maturation arrest subtypes. We observed no significant enrichment of MSY haplogroups in AZF- azoospermic patients (or its subtypes). However, we observed a strongly significant association between haplogroup J2a* and AZF+ patients (FDR-corrected p = .0056; OR = 7.02, 95%CI 1.89 to 39.20), a haplogroup which also showed significant enrichment for AZFa/b deletions (p = 4x10-4 ). We conclude that unlike AZF+ patients, AZF- NOA are less likely to have an MSY causative factor with large effect size, thus indicating that the aetiology of AZF- NOA, and to some extent AZFc NOA, is more likely to be based on non-MSY factors.
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Azoospermia , Infertilidade Masculina , Oligospermia , Azoospermia/genética , Estudos de Casos e Controles , Deleção Cromossômica , Cromossomos Humanos Y/genética , Haplótipos , Humanos , Infertilidade Masculina/genética , Masculino , Oligospermia/genéticaRESUMO
Recurrent hydatidiform mole is defined as episodes of two molar pregnancies in a female. Often, complete moles only derive androgenic nuclear genome. We described two cases with repeated molar pregnancies attempted to prevent future episodes by performing intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) to assess genetic disorders. The first patient had previously six complete molar pregnancies and advised to carry out ICSI with ovum donation to achieve a normal pregnancy. The second case had previously five molar pregnancies and no XY embryos from the ICSI/PGD process. We had to (at the insistence of the patient) transfer XX embryos in this patient which resulted in a complete hydatidiform mole (CHM). Hence, available data based on our patients and previous studies demonstrated that oocyte might play a critical role in the pathophysiology of recurrent hydatidiform mole, while it has not been often considered.
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OBJECTIVE: Nucleic acids released from the placenta into the mother's blood circulation system provide a valuable source of potential biomarkers for early detection of pregnancy complications such as preeclampsia (PE). PE affects nearly 5-10% of pregnancies worldwide and is a major contributor to the maternal and neonatal mortality and morbidity. It is known that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and ultimately lead to preeclampsia. The present study aimed to evaluate pattern of placental/fetal expression of the MMP family (MMP-2, MMP-9, MMP-14, MMP-15 and MMP-26) in preeclamptic women and compare it to normal pregnancies, using cell free fetal RNA (cff-RNA). METHODS: Blood samples were obtained from 20 pregnant women diagnosed with severe PE (28-32â¯weeks) and 40 control healthy pregnant women in two groups of either matched gestational age (Nâ¯=â¯20) or 14 and 28â¯weeks pregnancies (each 10). cff-RNA was extracted from plasma, followed by reverse transcription of cff-RNA. Expression of MMP genes was measured using quantitative reverse transcription PCR (qRT-PCR). RESULTS: The expression levels of MMP-2, MMP-9 and MMP-15 were significantly increased, while MMP-14 expression level was significantly reduced and the expression of MMP-26 showed a relative increase in PE pregnancies compared to the control group. Additionally, increased level of MMPs expression was observed by comparing 14 and 28â¯weeks gestation age in normal pregnancy. CONCLUSION: Using cff-RNA, circulatory expression level of MMP-2, MMP-9, MMP-14 and MMP-15 were significantly altered in preeclampsia compared to normal pregnancies.
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Ácidos Nucleicos Livres/sangue , Metaloproteinases da Matriz/genética , Pré-Eclâmpsia/diagnóstico , Diagnóstico Pré-Natal , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Feto/metabolismo , Regulação da Expressão Gênica , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Segundo Trimestre da Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
BACKGROUND: Microdeletions of the Yq chromosome are among the most frequent genetic etiological factor of male infertility which spans the azoospermia factor regions (AZFa, AZFb and AZFc). Microdeletions are mostly seen in the AZFc region and usually cover genes actively involved in spermatogenesis. Partial AZFc microdeletions may also occur with various spans, namely gr/gr, b2/b3 and b1/b3. It is known that the outcome of microtesticular sperm extraction (TESE), the surgical process for sperm retrieval from the testis in infertile azoospermic men, may be predicted based on the type of AZF microdeletion. We therefore aimed to evaluate the correlation between partial AZFc microdeletions and microTESE results. MATERIALS AND METHODS: In this cross-sectional study, 200 infertile azoospermic men referred to the Royan Institute were examined for the presence of partial AZFc microdeletions before undergoing microTESE. Partial AZFc microdeletions were detected by multiplex polymerase chain reaction (PCR) of seven different sequence-tagged site (STS) markers. The data were analyzed with the Chi-square test. RESULTS: Among the 90 patients (45%) with a positive microTESE outcome, 9 (10%) showed a partial microdeletion in AZFc region. Of the 110 (55%) patients with a negative microTESE outcome, 7 (6.3%) had an AZFc partial microdeletion. With respect to the span of the microdeletions, among the 200 patients, 11 (5.5%) were gr/gr and 5 (2.5%) were b2/b3. Statistical analysis showed no significant difference between the patients with and without partial AZFc microdeletions with respect to microTESE outcome. CONCLUSION: Partial AZFc microdeletions is not a predictor of microTESE outcome in azoospermic men.
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To evaluate the success rate in sperm retrieval (SR) through microdissection testicular sperm extraction (micro-TESE) in infertile azoospermia factor c (AZFc)-deleted men and determining their reproductive outcomes following ICSI, medical records of couples with AZFc-deleted male partners were reviewed on patient's age, serum hormone levels, karyotype, testicular pathology and pregnancy outcomes. A comparison on age and serum hormone level was conducted between groups with positive and negative sperm retrieval in both azoospermic and oligozoospermic AZFc-deleted men. Of 225 who had AZFc deletion, 195 cases followed clinical treatments. From 195 cases, 116 were azoospermic, 79 were oligozoospermic. Pathology profile was available in 103 of 195 subjects which the predominant trait was SCOS and was seen in 66.9% of cases (69 of 103). Success rate of sperm retrieval in azoospermic patients who underwent micro-TESE was 36.3% (28/77). Forty-three oligozoospermic and 17 azoospermic patients started ART cycle. Pregnancy rate in oligozoospermic group was 35.4% (17 cases), whilst there was no clinical pregnancy in azoospermic group. In conclusion, the pregnancy and delivery in oligozoospermic patients with AZFc deletion are comparable with other studies, but despite of sperm retrieval in azoospermic patients with AZFc deletion, the chance of pregnancy or delivery in these patients was very low.
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Azoospermia/terapia , Cromossomos Humanos Y/genética , Oligospermia/terapia , Recuperação Espermática , Adulto , Idoso , Azoospermia/genética , Feminino , Humanos , Irã (Geográfico) , Masculino , Microdissecção , Pessoa de Meia-Idade , Oligospermia/genética , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Testículo/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Microdeletions of the Y chromosome long arm are the most common molecular genetic causes of severe infertility in men. They affect three regions including azoospermia factors (AZFa, AZFb and AZFc), which contain various genes involved in spermatogenesis. The aim of the present study was to reveal the patterns of Y chromosome microdeletions in Iranian infertile men referred to Royan Institute with azoospermia/ severe oligospermia. MATERIALS AND METHODS: Through a cross-sectional study, 1885 infertile men referred to Royan Institute with azoospermia/severe oligospermia were examined for Y chromosome microdeletions from March 2012 to March 2014. We determined microdeletions of the Y chromosome in the AZFa, AZFb and AZFc regions using multiplex Polymerase chain reaction and six different Sequence-Tagged Site (STS) markers. RESULTS: Among the 1885 infertile men, we determined 99 cases of Y chromosome microdeletions (5.2%). Among 99 cases, AZFc microdeletions were found in 70 cases (70.7%); AZFb microdeletions in 5 cases (5%); and AZFa microdeletions in only 3 cases (3%). AZFbc microdeletions were detected in 18 cases (18.1%) and AZFabc microdeletions in 3 cases (3%). CONCLUSION: Based on these data, our results are in agreement with similar studies from other regions of the world as well as two other recent studies from Iran which have mostly reported a frequency of less than 10% for Y chromosome microdeletions.
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BACKGROUND: The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion. METHODS: Two-dimensional gel protein electrophoresis and MALDI-TOF were utilized in the analysis of fresh-frozen invasive intra-ductal carcinoma specimens. Calreticulin-associated expression was analyzed using immunohistochemistry of FFPE non-malignant/malignant breast specimens. A CRT-knockdown model of MCF7 cell line was developed using siRNA and the CRT genotype/phenotype correlations based on migration and trans-well invasion assays were determined. Finally, microarray-based global gene expression profiling was conducted to elucidate the possible calreticulin pro-invasive regulatory pathways. RESULTS: Two-dimensional gel protein electrophoresis and MALDI-TOF analysis showed upregulation of calreticulin expression in tumor tissues as compared to the normal adjacent tissues. Meta-analysis of the immunohistochemical results confirmed significantly higher expression of calreticulin (p < 0.05) in the stromal compartments of malignant tissues as compared to non-malignant tissues. Migration and transwell invasion assays showed significant loss in the migratory and invasive potential of CRT-knockdown cells (p < 0.05). Global gene expression profiling successfully identified various putative gene networks such as p53 and MAPK pathways that are involved in calreticulin breast cancer signaling. CONCLUSION: Besides confirming calreticulin overexpression in invasive breast cancer tissues, this study reveals a calreticulin-dependent pro-invasive potential and suggests possible contributing pathways. Defining the mechanistic role of invasion and characterizing the possible calreticulin-dependent molecular targets will be the focus of future work.
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Calreticulin (CRT) as a multi-functional endoplasmic reticulum protein is involved in a spectrum of cellular processes which ranges from calcium homeostasis and chaperoning to cell adhesion and finally malignant formation and progression. Previous studies have shown a contributing role for CRT in a range of different cancers. This present review will focus on the possible roles of CRT in the progression of malignant proliferation and the mechanisms involved in its contribution to cancer invasion.