International Journal of Reproductive BioMedicine
Year:2024 | Volume:22 | Issue:7|Papers Count:8

Background: Methadone is a substance widely used in the substitution treatment of opiate addiction in pregnancy. The placental transfer of methadone influences oxidative stress processes. Melatonin is a hormone with antioxidant activity. Objective: This study aimed to evaluate the protective effects of melatonin on oxidative stress induced by the transfer of transplacental methadone in mice. Materials and Methods: In this experimental study, 36 female mice (2 months old, 20 ± 2 gr) were divided into 6 groups (n = 6/each) of control, methadone (0.3 mg/kg intraperitoneal, single dose) and melatonin (2, 4, and 6 mg/kg/day gavage) were administered 30 min before methadone, and one group received melatonin alone (0.6 mg/kg with single injection). Administration for 10 consecutive days of the pregnancy period was done. After baby mice were born, all neonatal mice were killed by beheading or sacrificing after anesthesia. The liver tissues were extracted. The samples were then sent for studying oxidative stress markers such as lipid peroxidation, glutathione, and protein carbonyl contents. Also, we have used the immunohistochemistry method for apoptotic markers such as: BAX, Bcl2, and Caspase3 for assaying apoptosis. Results: This study has shown that methadone caused a significant decrease in glutathione concentration (p = 0.035). Also, we observed a significant increase in lipid peroxidation and protein carbonyl contents (p = 0.015, 0.025 respectively). However, melatonin treatment significantly inhibited oxidative stress markers (p = 0.025). Also, apoptosis assay has shown that melatonin could decrease BAX and Caspase 9 as apoptotic and increase Bcl2 as an antiapoptotic proteins (p = 0.015). Conclusion: Our findings have shown that melatonin has a protective effect against oxidative stress and apoptosis induced by the placental transfer of methadone via its antioxidant effects.

Background: Melatonin and L-carnitine are free radical scavengers with antiapoptotic and antioxidant properties that improve oocyte development. Objective: This study aimed to find the possible effect of combining 2 antioxidant agents of melatonin and L-carnitine on oocyte morphology, maturation, apoptosis, and expression of bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) genes in a mice model.  Materials and Methods: To overstimulation, 60 female NMRI mice were injected intraperitoneally using mare serum gonadotropin. On day 2 post-injection, 70 cumulus-oocyte complexes were collected from each mouse. The collected oocytes randomly were then divided into 4 groups including, the control, melatonin, L-carnitine, melatonin + L-carnitine groups. The morphology and maturation rate of the oocytes was evaluated using a light microscope. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and the expression of BMP-15 and growth and differentiation factor GDF-9 genes was also evaluated by real-time polymerase chain reaction. Results: Oocyte diameter significantly was increased in combination treatment of L-carnitine and melatonin compared to other groups (p < 0.05). L-carnitine group showed the highest mean percentage of oocyte cytoplasmic pattern. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling indicated that the lowest apoptosis rate belonged to the melatonin + L-carnitine group. Moreover, the combination groups showed the highest number of oocytes and maturation rate. The BMP-15 and GDF-9 genes were significantly upregulated in all treatment groups compared to the control group. Conclusion: Our results suggested a combination of melatonin + L-carnitine administration as a more effective choice for in vitro promotion of oocyte maturation.

Background: Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear. Objective: This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles. Materials and Methods: Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant. Results: Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage. Conclusion: The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Background: The toxicity of silver nanoparticles (AgNPs) has been proven in the female reproductive system. Thymoquinone (TQ) is a natural antioxidant and bioactive component of Nigella sativa. Objective: We evaluated the efficacy of TQ on ovarian tissue following toxicity induced by AgNPs in female mice. Materials and Methods: 24 female NMRI mice (5-6 wk, an average weight of 33 gr) were randomly divided into 4 groups (n = 6/each): control, AgNPs (500 mg/kg, gavage), TQ (2.5 mg/kg, intraperitoneal injection), and TQ+AgNPs. Mice were treated every day for 35 days. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), luteinizing hormone, and follicle-stimulating hormone were measured. The optical disector and stereological techniques were utilized to estimate the follicular count, their volume at different developmental stages, and the structure of ovarian tissue. Results: In the AgNPs group, the serum concentrations of TAC (p = 0.01), luteinizing hormone (p < 0.001), follicle-stimulating hormone, the volume of corpus luteum (p < 0.001), and the number of follicles decreased significantly compared to the control group. Nevertheless, AgNPs significantly increased the MDA level. In the TQ+AgNPs group compared to the AgNPs group, a significant decrease in MDA level (p < 0.001) and a significant improvement in TAC (p = 0.03), and hormonal levels, the number of primary, preantral, and antral follicles (p = 0.04), and the volume of corpus luteum (p = 0.01) were observed. Conclusion: TQ improved the number of follicles by reducing oxidative stress and lipid peroxidation in AgNPs-damaged ovarian tissue.

Background: The lack of improvement in some endometriotic people’s pain after surgery even while using hormone treatment may suggest an inappropriate response to routine hormonal therapies. Objective: This study aimed to determine a cut-off point for selecting the most appropriate treatment based on the hormone receptors of endometriotic lesions. Materials and Methods: In this cross-sectional study, by reviewing the medical records of participants and testing their archive samples and phone interviews (if needed), 86 symptomatic women after endometriosis surgery who were operated into governmental hospitals, Shahid Faghihi and Hazrate Zeinab Shiraz Iran were enrolled between March 2017 and March 2019. Women were divided into 2 groups: responsiveness (n = 73 for dysmenorrhea, n = 60 for dyspareunia) to medical treatment and surgery, and unresponsiveness (n = 13, n = 7). We examined the pathological slides of 86 women to determine the amount of hormone receptors and the relationship between the type of medical treatment and the level of hormone receptors on pain relief within 1 yr after surgery. Results: Based on the receiver operating characteristic curve, dysmenorrhea in the presence of tissue estrogen receptors > 60% (p = 0.1065), and dyspareunia in the presence of tissue progesterone receptors > 80% (p = 0.0001) responded well to medical treatment after surgery. In the presence of endometrioma-dysmenorrhea showed the best response to oral contraceptive pills (69.4%), while in deep infiltrative endometriosis-dyspareunia showed the best response to progesterone treatment (75%). Conclusion: Prescribing an appropriate hormone therapy based on a specific immunohistochemistry staining pattern can improve the life quality of postoperative endometriosis individuals.

Background: Opioid analgesics like morphine and methadone are widely used for managing severe pain; however, concerns over their potential misuse and adverse effects on the brain and reproductive system are significant. Objective: We aimed to investigate their impacts on spermatogenesis and cognitive function in male Norway rats. Materials and Methods: In this experimental study, 36 male Norway rats (250-300 gr, 6 months old) were divided into 6 groups: low-dose morphine, high-dose morphine, low-dose methadone, high-dose methadone, positive control (received normal saline at 5 mg/kg), and negative control (received no treatment). Morphine and methadone were administered intraperitoneally over 30 days at doses of 3 mg/kg and 7 mg/kg, respectively. Behavioral assessments evaluated anxiety, stress, and short- and long-term memory. Sperm parameters (viability, motility, morphology), hormonal analysis (testosterone, luteinizing hormone, follicle-stimulating hormone, estradiol), and gene expressions (Tp53, CatSper1) were assessed. Results: A significant reduction in rat weight was observed in the high-dose morphine group (p = 0.0045), while testicular weights remained unchanged. Sperm abnormalities were observed with high doses of methadone and morphine. High-dose methadone significantly reduced offspring count (p = 0.0004). Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol varied significantly across treatment groups. Gene expression was altered in response to treatments (p < 0.05). Conclusion: Prolonged exposure to methadone and morphine resulted in memory dysfunction, chronic stress, hormonal disturbances, altered gene expression, and fertility complications. These effects were more pronounced at higher doses, highlighting the importance of careful dosage management in opioid therapy.

Background: Natural killer (NK) cells play a critical role in the pathogenesis of endometriosis. Moreover, a normal vitamin D level is remarkably associated with an optimal immune response. So, there may be a probable relationship between these factors and the endometriotic women. Objective: This study aimed to evaluate the percentage of NK cells and their subsets and their relationship with serum levels of vitamin D and interferon gamma (IFN-γ) in women with endometriosis. Materials and Methods: In this case-control study, 29 women with stage III-IV endometriosis and 30 healthy controls were enrolled. The study was conducted in the Immunology Department of Isfahan University of Medical Sciences, Isfahan, Iran between November 2021 and June 2022. The percentage of NK cells and their subsets, including CD56dim CD16+, CD56bright CD16- and CD56bright CD16bright were measured in the peripheral blood samples using flow cytometry. Serum levels of vitamin D and IFN-γ were also measured using the enzyme-linked immunosorbent assay. Results: The mean percentage of NK cells in women with endometriosis increased significantly compared to the control group (p = 0.03). The percentage of CD56dim CD16+ (p = 0.007) and CD56bright CD16 bright (p = 0.043) increased significantly in women with endometriosis in comparison with the control group, but the percentage of CD56bright CD16- subset was not significantly different. No relationship was observed between NK cells and their subsets with vitamin D and IFN-γ in the studied groups. Conclusion: The study of NK cell subsets and their related factors can be useful in assessing and treating women suffering from endometriosis. However, more comprehensive studies are required to draw definitive conclusions about these observations.

Dear Editor, Recently, Elahi et al., published an article entitled above and concluded that the varicocele negatively affects sperm concentration, motility, morphology, sperm DNA fragmentation index, mitochondrial membrane potential level, and adenosine triphosphate (1). However, we believe that the conclusion is doubtful due to the following reasons: 1. Talking about any causality effect in the cross-sectional studies is forbidden, because exposure and outcome are assessed at the same time and may be susceptible to reverse causality (2).