PTEN promoter methylation and expression in endometrial cancer tissues.

Introduction: Some gene expression regulation in cancers can be controlled by epigenetic change like methylation. PTEN promoter methylation and expression were evaluated in endometrial cancer. Methods: The study was run on 39 tumor tissues of endometrial cancer patients and 41 normal endometrial tissues. After total RNA extraction, cDNA synthesis was done by reverse transcription of the total (real-time PCR) using SYBER Green master mix. DNA extraction and bisulfite treatment were conducted and methylation was semiquantified by the methylation-sensitive high-resolution melting method. Finally, promoter methylation quantification of the total number of 25 tumors and 22 non-neoplastic tissues was done. Results: PTEN gene expression showed a significant decrease in endometrial cancer tissues. Promoter methylation was significantly lower in the non-neoplastic group (7.2; p < 0.001). In addition, PTEN promoter methylation was observed in 52.0% of tumor tissues compared with 13.6% in the non-neoplastic group (p = 0.06). There were no significant correlations between PTEN expression and methylation and clinicopathological features in endometrial cancer patients (p > 0.05). Conclusion: PTEN gene expression in endometrial cancer tissues decreased because of its promoter hypermethylation.

Quality of Life in Breast Cancer Patients: A Systematic Review of the Qualitative Studies.

OBJECTIVE: Quality of life (QoL) in breast cancer patients is still an important topic. Despite numerous quantitative scales, qualitative studies can help to in-depth understand the QoL of breast cancer patients. The purpose of this systematic review was to integrate qualitative studies on the QoL of women with breast cancer. METHODS: A literature search was performed in electronic databases including PubMed, Scopus, and Web of Science from January 1, 2010 until June 28, 2022 to find out qualitative studies assessing breast cancer patient's QoL. Two authors independently evaluated methodological quality according to the consolidated criteria for reporting qualitative research (COREQ) checklist. Data were extracted and reported by themes for cancer-free women and patients with metastatic cancer separately. RESULTS: In all, 1565 citations were retrieved. After removing 1387 duplicate and irrelevant papers, the full texts of 27 articles were reviewed and finally, 9 were eligible for evaluation. In quality checking of the citations, all articles gained the required quality score. After examining and merging similar topics, nine major themes were extracted. Physical, spiritual, and psychological aspects of QoL were the common issues in cancer-free women (before and after the COVID-19 pandemic) and patients with metastatic cancer. Perception of cancer and social life were the other main concerns in cancer-free women, whereas, in metastatic patients' overall survival and planning for the future and their children's life was the focus of interest. Women with metastatic disease showed more vulnerability in coping compared to cancer-free women. CONCLUSION: This review provides an opportunity to have a closer look into the several domains of QoL in women with breast cancer. In-depth information provided by this review might help to develop interventions for patients and their families to support women to cope much better with their life challenges.

Reproductive health of women with endometriosis: an improving educational intervention based on the planned behavior theory.

Background: Endometriosis is a chronic deliberating disease with devastating effects on reproductive health. The present study aimed to investigate the impact of education based on the theory of planned behavior (TPB) on the reproductive health of women with endometriosis. This research was a randomized controlled trial performed on 71 women with endometriosis (35 intervention and 36 control groups) referred to the infertility clinic of Imam Khomeini Hospital in Tehran, Iran. The educational intervention based on the structures of the TPB was performed in the intervention group in 4 sessions, weekly for 90-120 min. The demographic questionnaire, model constructs questionnaire, and endometriosis reproductive health questionnaire (ERHQ) in both groups were completed in 3 stages (before intervention, 4, and 8 weeks after the intervention). Data were analyzed using SPSS software version 24. Results: After the educational intervention, TPB values and overall reproductive health of women with endometriosis improved significantly in the intervention group (p < 0.05), while changes were not significant in the control group. Conclusion: The study results showed that education based on the TPB had positive effects on the reproductive health of patients. Trial registration: IRCT20120414009463N64. Registered 21 Jun 2021 - Retrospectively registered, http://www.irct.ir/trial/53341. Supplementary Information: The online version contains supplementary material available at 10.1186/s43043-023-00129-7.

The impact of letrozole on oocyte quality in assisted reproductive technology (ART); a randomized double-blind clinical trial.

OBJECTIVE: To examine the effect of letrozole on oocyte quality and pregnancy outcome in assisted reproductive technology (ART). METHODS: This double blind placebo controlled clinical trial was conducted in Vali-Asr Infertility Center. Infertile women candidate for IVF that underwent antagonist protocol were selected. Eligible women randomly allocated into treatment (letrozole/Let group) and control (placebo) group. Participants received letrozole 5 mg/day or placebo at the time of gonadotropin start until trigger day in the same manner. Number of oocyte retrieved, metaphase II oocyte number, high grade oocyte number (G1), high quality embryo, Chemical and clinical pregnancy rate and OHSS (ovarian hyperstimulation syndrome) rate was recorded. 216 infertile women (104 in letrozole and 112 in the control group) were evaluated. RESULTS: In the Let group estradiol level was significantly lower (p_value < .001) and testosterone significantly higher than in the control group (p_value = .02). The number of retrieved oocytes, MII oocytes, G1 oocytes, and 2PN was significantly lower in the Let group (p < .05). No significant difference was found in the day of stimulation, total gonadotropin dose, OHSS rate, and clinical pregnancy rate between the two groups (p > 0.05). CONCLUSIONS: According to the results, letrozole may reduce oocyte quality and cause poor IVF outcomes as well.

The Effect of COVID-19 Pandemic on Outcome of Assisted Reproductive Technology: A Report from a Single Infertility Center.

Objective: COVID-19 pandemic has affected all aspects of human life including social, economic, healthy behaviors and even individual relationships. This study aimed to investigate the effect of corona virus outbreak on assisted reproductive technology (ART) outcome. Materials and methods: In this retrospective and prospective cohort, 260 ART cycles of ovum pick up (OPU), fresh embryo transfer (ET) and frozen embryo transfer (FET) were evaluated in 223 women (from December 2019 to February 2020) and during COVID-19 outbreak (February and July 2020) in an infertility center. Primary and secondary outcomes of ART cycles including chemical and clinical pregnancy rate were evaluated. Results: The mean±SD (standard deviation) age of women was 34.17±6.56 years. Chemical and clinical pregnancy rates were 23.91% (33/138) per embryo transfer and 75.8% (25/33) per positive pregnancy test, respectively while ongoing pregnancy was seen only in 69.7% (23/33) of those with positive pregnancy test. Spontaneous abortion rate was 15.15% (5/33) per laboratory pregnancy. COVID-19 symptoms were reported in 2.83% and 15.38% of women during and after ART cycles, respectively. Conclusion: It seems that COVID-19 pandemic has not negative effect on outcome of ART cycles except for cancelation rate due to COVID-19 that increased at the beginning of COVID-19 outbreak as it was unknown at that time and awareness was limited.

Maternal and neonatal outcomes of pregnancies of infertile women during the COVID-19 pandemic: a real world evidence.

OBJECTIVE: The COVID-19 pandemic began in Dec. 2019 and its effects on pregnancy outcomes are still unknown. This study aimed to evaluate the pregnancy outcomes of infertile women who conceived during the COVID-19 pandemic. METHODS: This cross-sectional study included infertile women who conceived during the COVID-19 pandemic. Infertile women referred to the infertility center at the Vali-e-Asr hospital who conceived spontaneously or with the aid of ART (IUI, ICSI) were included and followed until delivery or pregnancy termination. RESULTS: A total of 38 pregnant women (34 conceiving after ART and four spontaneously) were included. Seventeen (44.74%) of the 38 pregnant women developed COVID-19 symptoms. No significant difference was detected in maternal and neonatal outcomes, including miscarriage, PROM, low birth weight, or premature birth between pregnancies with and without COVID-19 symptoms. A significant difference was found between the two groups in delivery route. CONCLUSIONS: No associations were found with maternal and neonatal morbidity in women conceiving during the COVID-19 pandemic and in pregnant women with and without COVID-19 symptoms.

Maternal and Neonatal Complications, Outcomes and Possibility of Vertical Transmission in Iranian Women with COVID-19.

BACKGROUND: The emergence and fast spread of coronavirus disease 2019 (COVID-19) threatens the world as a new public health crisis. Little is known about its effects during pregnancy. This study aimed to investigate the clinical manifestations of COVID-19 on maternal and neonatal outcomes. METHODS: In this systematic review, PubMed, Scopus, Web of Science, and Google Scholar databases were searched focusing on pregnancy and perinatal outcomes of COVID-19. RESULTS: The initial search yielded 1236 articles, from which finally 21 unique studies, involving 151 pregnant women and 17 neonates, met the criteria. Mean ± SD age of included mothers and mean ± SD gestational age at admission were 30.6 ± 6.2 years and 30.8 ± 8.9 weeks, respectively. The common symptoms were fever, cough, fatigue, dyspnea and myalgia. The mortality rates of pregnant women and neonates were 28 out of 151 (18.5%) and 4 out of 17 (23.5%), respectively. Most of the neonates were preterm at the time of delivery. Three neonates had positive RT-PCR test on the first day after birth and three others on day two. On the average, neonate's PCR became positive on day 4 for the first time. CONCLUSION: Early diagnosis of COVID-19 is crucial due to the possibility of the prenatal complications. Strict prevention strategies may reduce the risk of mother to infant transmission.

Clinical and Molecular Effects of GnRH Agonist and Antagonist on The Cumulus Cells in The In Vitro Fertilization Cycle.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) analogues have been extensively utilized in the ovarian stimulation cycle for suppression of endogenous rapid enhancement of luteinizing hormone (LH surge). Exclusive properties and functional mechanisms of GnRH analogues in in vitro fertilization (IVF) cycles are clearly described. This study was performed to evaluate clinical and molecular impacts of the GnRH agonist and antagonist protocols in IVF cycles. For this purpose, gene expression of cumulus cells (CCs) as well as clinical and embryological parameters were evaluated and compared between two groups (GnRH agonist and antagonist) during the IVF cycle. MATERIALS AND METHODS: Twenty-one infertile individuals were enrolled in this study. Subjects were randomly allocated into two groups of GnRH agonist (n=10) treated patients and GnRH antagonist (n=11) treated individuals. The defined clinical embryological parameters were compared between the two groups. Expression of BAX, BCL-2, SURVIVIN, ALCAM, and VCAN genes were assessed in the CCs of the participants using the real-time polymerase chain reaction (PCR) technique. RESULTS: The mean number of cumulus oocyte complex (COC), percentage of metaphase II (MII) oocytes, grade A embryo and clinical parameters did not show noticeable differences between the two groups. BAX gene expression in the CCs of the group treated with GnRH agonist was remarkably higher than those received GnRH antagonist treatment (P<0.001). The mRNA expression of BCL-2 and ALCM genes were considerably greater in the CCs of patients who underwent antagonist protocol in comparison to the group that received agonist protocol (P<0.001). CONCLUSION: Despite no considerable difference in the oocyte quality, embryo development, and clinical outcomes between the group treated with GnRH agonist and the one treated with antagonist protocol, the GnRH antagonist protocol was slightly more favorable. However, further clinical studies using molecular assessments are required to elucidate this controversial subject.

Investigation of the FSHR, CYP11, and INSR Mutations and Polymorphisms in Iranian Infertile Women with Polycystic Ovary Syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of ovarian dysfunction associated with infertility, Oligomenorrhea or amenorrhea, hirsutism, acne, and obesity. A large body of evidence unraveled, three major groups of genes play critical roles in underlying PCOS molecular mechanism. The aim of this study is to investigate critical exonic variant of FSHR, CYP11, and INSR and determine the functionality of these mutations in Iranian patients with PCOS. METHODS: In this case-control study, 130 patients with PCOS who referred to the Vali-e-Asr Hospital with infertility were included. DNA extracted from three ml of peripheral blood of the participants for DNA extraction. The PCR was conducted for each gene and the PCR product was genotyped by sequencing. RESULTS: The data showed that there were two polymorphisms in INSR genes which did not change the protein sequences; these alterations can also be considered as a single nucleotide polymorphism (SNP). Moreover, any exonic variant has not been detected in CYP11B1. Whereas, two missense mutation have been detected in FSHR gene including p.Ala307Thr and p.Asn680Ser. It has been shown that the polymorphisms of the FSHR gene affect the hormone response in the ovaries. Our data demonstrated that the FSHR mutations frequencies were higher in the patients with PCOS rather than control people significantly. CONCLUSION: These data showed that the polymorphisms of FSHR were significantly associated with PCOS in Iranian infertile women. Further studies with larger sample sizes are needed to be performed for explore the strength of the association.

Comparing a biosimilar follitropin alfa (Cinnal-fⓇ) with Gonal-fⓇ in women undergoing ovarian stimulation: An RCT.

BACKGROUND: Advances in recombinant DNA technology led to the development of recombinant follitropin alfa. Recombinant human follicle-stimulating hormone products are used to stimulate follicular maturation. OBJECTIVE: To compare the efficacy and safety of a biosimilar-candidate recombinant human follicle-stimulating hormone (Cinnal-fⓇ; CinnaGen, Iran) with the reference product (Gonal-fⓇ; Merck Serono, Germany) in women undergoing ovarian stimulation for intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: In this randomized controlled trial, a total sample size of 200 women (age < 35 yr, candidate for ICSI) was calculated. Participants began a pituitary downregulation protocol with buserelin. They received 150 IU daily of either Cinnal-fⓇ or Gonal-fⓇ from the second day of their cycle. The primary outcome of the study was the percentage of metaphase II (MII) oocytes. The secondary outcomes included the number and quality of oocytes retrieved, duration of stimulation, fertilization rate, embryo quality, the number of clinical and ongoing pregnancies, and the incidence of ovarian hyperstimulation syndrome (as an important safety marker). RESULTS: A total of 208 women were enrolled, of whom, 200 completed the study period. Ovarian stimulation with Cinnal-fⓇ resulted in a comparable percentage of MII oocytes as with Gonal-fⓇ (78.64% vs 80.02%, respectively; p = 0.81). No statistically significant difference was seen in the secondary outcomes between the groups. CONCLUSION: Cinnal-fⓇ proved non-inferior to Gonal-fⓇ, based on the percentage of MII oocytes in women aged < 35 yr undergoing ICSI. Our findings confirm that the efficacy and safety profiles of Cinnal-fⓇ and Gonal-fⓇ are similar.

Infertility policy analysis: a comparative study of selected lower middle- middle- and high-income countries.

BACKGROUND: Infertility has recently become a salient but neglected global issue. Policies to address the sexual and reproductive health and rights (SRHR) are vital, especially in lower middle and middle-income countries (LMICs). Hence, the aim of this study was to compare the national infertility policies in the selected countries (LMICs comparing with high-income) to determine gaps or to confirm desirable policies in the given health systems. METHODS: This study has executed a comparative policy analysis of infertility services using the universal health coverage framework (financial protection, population coverage, and service features) in three scopes (prevention, treatment, and supportive care). Seven countries that had infertility programs in their health sectors were selected. RESULTS: The results showed that financial protection was good in high and middle-income countries, but in a lower middle income, and in one high-income country was poor. The findings also showed that health systems in the same countries had no infertility services for men. Preventive and supportive care services were neglected in LMICs by governments. CONCLUSION: The findings indicate that income is not the only factor that fulfills universal health coverage for infertility care services. Perhaps to achieve equity in infertility care services, it should be seen as a universal human right to accomplish the right to have a child and to have a life with physical and mental health for all men and women.

Comparison of Dydrogesterone and GnRH Antagonists for Prevention of Premature LH Surge in IVF/ICSI Cycles: A Randomized Controlled Trial.

Objective: To compare the effect of dydrogesterone and Gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge and pregnancy outcomes in infertile women undergoing Invitro fertilization/ Intra cytoplasmic sperm injection (IVF/ICSI). Materials and methods: In a Randomized controlled trial (RCT), two-hundred eligible women undergoing in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) treatment were randomly assigned into two groups. Human menopausal gonadotropin (HMG) was administered for controlled ovarian stimulation (COS) in both groups. Intervention group (group 1) received 20 mg dydrogesterone from day 2 of menstrual cycle till trigger day and control group (group2) received GnRH antagonist from the day that leading follicle reached 13 mm in diameter till trigger day. Serum levels of LH, estradiol and progesterone were measured on the trigger day. The primary outcome measure was the incidence of a premature LH surge, and the secondary outcomes investigated were the chemical and clinical pregnancy rates in the first FET cycles. Results: There were no significant differences in patients' age, BMI, AMH levels, previous IVF cycle, and cause of infertility between the two groups. None of the patients in two groups experienced a premature luteinizing hormone surge. The numbers of retrieved oocytes, the MII oocytes and good quality embryos, were significantly higher in the intervention group than antagonist group (p < 0.05). The overall chemical pregnancy rate in intervention group (43/91: 46.2%) and control group (45/91: 49.5%) (p = 0.820) was similar. Meanwhile, the clinical pregnancy rate was similar between groups too. Conclusion: Regarding the cost, efficacy and easy usage of dydrogestrone, it may be reasonable to use it as an alternative to GnRH antagonist for the prevention of premature LH surge.

Effects of Selenium Supplementation on Asymmetric Dimethylarginine and Cardiometabolic Risk Factors in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is characterized by various reproductive and cardiometabolic disorders. Asymmetric dimethylarginine (ADMA) is associated with cardiovascular, metabolic, and hormonal status. Selenium, a micronutrient with antioxidant properties, could affect multiple physiological pathways. This study aimed to investigate the effect of selenium supplementation on ADMA, cardiometabolic risk factors, and hormonal status in women with PCOS. In this randomized, double-blind, placebo-controlled clinical trial, 66 women with PCOS, aged 18-45 years, were randomly assigned to receive either 200 µg/day selenium or placebo, for 12 weeks. Circulating concentrations of ADMA, testosterone, sex hormone-binding globulin (SHBG), lipid profiles, and glycemic parameters were assessed at baseline and following supplementation. ADMA concentration decreased significantly compared to baseline values (85.14 ± 75 to 56.4 ± 38.64 ng/l, p = 0.02) in the selenium group. This change was marginally significant compared with the placebo group (28.74 ± 68.63 vs. - 1.77 ± 52.88 ng/l, p = 0.056). Serum testosterone levels declined significantly in the intervention compared to the placebo group (0.01 ± 0.17 vs. - 0.08 ± 0.18 ng/ml, p = 0.038). Pre- to post-Apo-B100/Apo-A1 ratio declined considerably in the intervention group (0.72 ± 0.16 to 0.65 ± 0.16, p = 0.003). No further differences were observed in SHBG, lipid profiles, Apo-A1, Apo-B100, Apo-B100/Apo-A1 ratio, and glycemic control between the two groups at the end of the study. Selenium supplementation for 12 weeks had beneficial effects on reduction of circulating ADMA and total testosterone levels in women with PCOS. No significant improvements were seen in other cardiometabolic risk factors. The effects of selenium supplementation on hormonal, reproductive, and cardiometabolic disorders, considering the potential mediating role of ADMA, should be further investigated.

Luteinizing hormone changes in gonadotropin-releasing hormone antagonist protocol in in vitro fertilization cycles: A cross-sectional study.

BACKGROUND: Because of the unexpected and often dramatic inhibition of luteinizing hormone (LH) secretion related with the usage of gonadotropin-releasing hormone (GnRH)-antagonist, there has been a probable need for exogenous LH supplementation. There is a basic and clinical evidences that show late development of follicle needs an LH but there is a threshold for LH requirements during folliculogenesis. OBJECTIVE: The purpose of this study was to evaluate the changes in serum LH and the identification of patients who benefit from the addition of LH. MATERIALS AND METHODS: Seventy volunteers for antagonist protocol in IVF cycle were enrolled in this prospective cross-sectional study. The study was carried out in Reproductive Health Research Center, University of Medical Sciences between July 2016 and February 2016. Serum LH level was estimated 24 h before and after the first (GnRH) antagonist injection. The primary outcome was the serum level of LH and its change in the three groups and the secondary outcome was Egg and Embryo quality. RESULTS: LH changes above or below 50% had no effect on the number of follicle, the number of oocyte, Germinal vesicle oocyte, metaphase 1 oocyte, metaphase 2 oocyte, endometrial thickness, and chemical and clinical pregnancy. CONCLUSION: We evaluated the changes of serum LH in the patients who were entered in the antagonist protocol. Our study showed no significant difference in LH levels 24 h before and after the injection of the antagonist between the three groups, and LH changes did not affect the outcome of pregnancy.

The sequential embryo transfer compared to blastocyst embryo transfer in in vitro fertilization (IVF) cycle in patients with the three repeated consecutive IVF. A randomized controlled trial.

The purpose of this study was to determine the pregnancy rate in the double sequential transfer of embryos on both day 3 and day 5 compared to day 5 alone, in in vitro fertilization-embryo transfer (IVF/ET) in patients with the three repeated consecutive IVF failures. In this controlled trial, women scheduled for IVF/ET with the three repeated consecutive IVF failures were randomized to either sequential transfer of embryos on day 2 and on day 5 after ovum pick-up (group 1, n = 60) or blastocyst ET on day 5 (group 2, n = 60) as a control group. The primary outcome measures were the chemical and clinical pregnancy rate. Baseline and cycle characteristics were comparable in both groups. Chemical and clinical pregnancy rate was similar in the sequential ET group (40%) compared to the day 5 of ET group (38.3%) (p value = .85). It seems that the double ET does not increase the chance of pregnancy rate compared to blastocyst ET on day 5 in the patients with the three repeated IVF-ET failures.

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case-control study.

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) - 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the - 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that - 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis.

The Association Analysis of Vascular Endothelial Growth Factor -2549 Insertion/ Deletion Variant and Endometriosis Risk.

Endometriosis is a debilitating disorder, defined as the presence of endometrial gland and stroma outside of the uterus. It may affect angiogenesis and vascular endothelial growth factor (VEGF) is one of the angiogenic factors that plays an important role in both physiological and pathological angiogenesis. The present study aimed to evaluate the association of VEGF -2549 insertion/deletion (I/D) polymorphism with endometriosis. This case-control study enrolled 244 (100 cases and 144 controls) women who were admitted for laparoscopy or laparotomy for gynecological procedures. Genomic DNA was separated from peripheral blood leukocytes and polymerase chain reaction (PCR) amplification was performed for genotyping of the VEGF gene Insertion/Deletion (I/D) polymorphism. The frequency of the II, ID, and DD genotype was 14%, 52% and 34% in patients versus 18.8%, 47.8% and 34% in controls. The results did not provide any evidence supporting the endometriosis risk related to the VEGF polymorphism in a group of Iranian women population.

Gonadotropin Regulation of Retinoic Acid Activity in the Testis.

Initiation of spermatogenesis in primates is triggered at puberty by an increase in gonadotropins; i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prior to puberty, testis of the monkey contains only undifferentiated germ cells. However, sermatogonial differentiation and spermatogenesis may be initiated prior to puberty after stimulation with exogenous LH and FSH. Retinoic acid (RA) signaling is considered to be a major component that drives spermatogonial differentiation. We were interested in evaluating the relative role of LH and FSH, either alone or in combination, in regulating the retinoic acid signaling in monkey testis. Sixteen juvenile male rhesus monkeys (Macaca mulatta) were infused with intermittent recombinant single chain human LH (schLH) or recombinant human FSH (rhFSH) or a combination of both for 11 days. We then analyzed the expression of the several putative RA signaling pathway related genes; i.e. RDH10, RDH11, ALDH1A1, ALDH1A2, CYP26B1, CRABP1, CRABP2, STRA6, STRA8 in the testis after 11 days of stimulation with vehicle, LH, FSH and combination LH/FSH using quantitative real-time PCR (qPCR). The qPCR results analysis showed that administration of gonadotropins affected a significant change in expression of some RA signaling related genes in the monkey testis. The gonadotropins, either alone or in combination dramatically increased expression of CRABP2 (p≤0.001), whereas there was a decrease in ALDH1A2 expression (p≤0.001). Moreover, combined gonadotropin treatment led to the significant decrease in CRABP1 expression (p≤0.05). These findings are the first evidence that the activity of retinoic acid signaling in the monkey testis is regulated through gonadotropins (LH/FSH) levels.

Comparing reactive oxygen species and DNA fragmentation in semen samples of unexplained infertile and healthy fertile men.

BACKGROUND: Male factor infertility has increased to more than 40% during the last decade. About 30% of these couples are diagnosed with unexplained infertility. In fact, reactive oxygen species (ROS), especially superoxide anion (O2-·) and hydrogen peroxide (H2O2), play a crucial role in regulation of physiological and pathological processes in spermatozoa. Moreover, since the diagnosis of unexplained infertility just through semen analysis is a matter of much controversy; we aimed to evaluate the levels of ROS and sperm DNA fragmentation in the semen samples of unexplained infertile and fertile control couples. METHODS: The semen samples of 28 unexplained infertile couples and 30 fertile control couples were analyzed according to WHO criteria. The intracellular levels of H2O2 and O2-· were detected by flow cytometry with 2',7'-Dichlorodihydrofluorescin diacetate and Dihydroethidium, respectively, and DNA fragmentation was evaluated by sperm chromatin dispersion test. RESULTS: In unexplained infertile group, sperm motility and normal morphology were significantly lower than the control. The levels of sperm H2O2, O2-·, and DNA fragmentation were significantly higher in unexplained infertile men compared to fertile. Moreover, a positive correlation was found between the level of H2O2 and sperm DNA fragmentation in the unexplained infertile group. Besides, reduced sperm motility in the unexplained infertile group was significantly correlated with elevated levels of ROS. CONCLUSIONS: The higher levels of intracellular ROS and DNA fragmentation in the semen samples of unexplained infertile couples and their causes might be considered as an important factor related to diagnosis and treatment of the unexplained infertile couples.