Cell Journal (Yakhteh)
Volume:26 Issue: 4, Apr 2024

The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome(PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) geneshave been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to theoocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs ofPCOS, with or without insulin resistance. In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive(IS), and control (fertile women with male infertility history) groups. The expression of NCF2, TXNIP, UCP2,NDUFB6, ATP5H, COX7C, NDUFA3, SDHA, and SDHB was studied by real-time polymerase chain reaction (PCR),aand normalization was performed considering HPRT1 and CYC1 as reference genes. One-way ANOVA and Tukey testwere used for data analysis. The results showed that the expression of NCF2, TXNIP, UCP2, and ATP5H was significantly higher in theIR group than IS and control groups (P<0.01). NDUFB6 showed the highest expression in the IS group, which wassignificantly different from other groups (P<0.01). The other genes of interest, except COX7C, were observed with themost transcriptional levels in the IS group, although there was no significant difference for those genes. Altered expression of genes involved in mitochondrial function compared to the control group in CCsof both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to thepathophysiology of PCOS.

Endometriosis, as a common inflammatory chronic disease is characterized by endometrial tissue growthoutside the uterine cavity. It was reported that lipopolysaccharides (LPS) activate a transcription factor called LPSinduced tumor necrosis factor-alpha (LITAF) in macrophages, which induced transcription of cytokine genes suchas tumor necrosis factor alpha (TNF-α). B-cell lymphoma 6 protein (BCL6) is a transcription factor which expressionwas increased in endometrial tissues of infertile women with endometriosis. In addition, it was shown that mRNA andprotein of LITAF and BCL6 were inversely related in mature B lymphocytes and B-Cell lymphomas. Accordingly, weinvestigated gene expression of LITAF, BCL6 and TNF-α in eutopic and ectopic endometrial tissues of women withendometriosis compared to the controls. In this case-control study, 10 women with endometriosis (endometriosis group) and 10 women without endometriosis (control group) enrolled after diagnostic laparoscopy. Real-time polymerase chain reaction (PCR) technique was used to quantitatively analyze gene expression. One-Way ANOVA was used for data analysis. This study showed that LITAF gene expression was significantly higher in ectopic endometrial tissuescompared to the control samples. Expression level of BCL6 gene was significantly increased in the ectopic tissuesof women with endometriosis compared to the control and eutopic samples. Although TNF-ɑ gene expression wasincreased in the ectopic lesions compared to the eutopic and control endometrial samples, these differences were notsignificant. The results suggested that over-expression of these inflammatory genes in ectopic endometrial lesionscan be considered as a molecular scenario in pathophysiology of endometriosis by induction of inflammatory cascades and cellular proliferation.

Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in theRB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavityor in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predictedearly, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumorsseparately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separatingmiRNAs in blood serum from invasive and non-invasive RB patients. In this experimental study, selected three gene expression omnibus (GEO) datasets. Twowere related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression.Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidatemiRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma. Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373,and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. OnlyMiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomasincreased serum miR-20a and miR-191. Integrated and regular bioinformatics analyses found important miRNAs in patients’ and miR-20a, miR-191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur afteradministration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule withanti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model ofOHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictorproteins and ovarian histological changes in an experimental OHSS rat model. In this experimental study, 30 adult female rats (two months old) were randomly divided intosix groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days),iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascularendothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone(P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes. Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atreticfollicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of theVEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantlyattenuated all molecular and histological alterations observed in the OHSS animals. Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patientsby reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings aresimilar to CAB and can be a new avenue for future research on BET.

This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrationswith alterations in the expressions of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 genes and the number ofretrieved mature oocytes (MII oocyte) in the cumulus cells of infertile poor ovarian response stimulates women.In this prospective cohort study, 80 infertile unexpected poor ovarian response (POR) subjectswere selected on the basis of subgroup 1a of the POSEIDON classification. They were divided into two groups: group1 consisted of 40 women, each with a higher number of metaphase II (MII) oocytes (G1, 3-4 oocytes retrieved), whilegroup 2 comprised of 40 women, each with a lower number of MII oocytes (G2, ≤2 oocytes retrieved). The expressionsof the studied genes were evaluated by quantitative-real time polymerase chain reaction (PCR). The concentration ofBPA in follicular fluid was measured with HPLC. The expression levels of NOTCH1-3, HLA-G, and ICAM-1 genes were significantly lower in G2 than G1(P<0.05). Meanwhile, CASPASE 3/7 expression levels were higher in unexpected POR patients in G2 compared toG1 (P<0.05). There was a significant direct correlation between the levels of NOTCH1-3, HLA-G and ICAM-1 geneexpressions and there was also a significant inverse correlation (P<0.05) between the levels of CASPASE 3/7, with thenumber of MII oocytes and embryo development between the two groups. The concentration of BPA in the follicularfluids of G2 was higher compared to G1 (P<0.05). A higher concentration of BPA was associated with a lower number of mature oocytes and oocyte qualityin these patients. Also, alterations of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 transcript levels in unexpectedPOR women were associated with BPA concentration.

In this article published in Cell J, Vol 26, No 1, 2024, on pages 81-90, the authors found that the affiliation of authorsin address 1 and also the two corresponding authors had accidentally missed during the formatting of the paper.Therefore, we corrected them.The authors would like to apologize for any inconvenience.