Effects of coadministration of DHA and vitamin E on spermatogram, seminal oxidative stress, and sperm phospholipids in asthenozoospermic men: a randomized controlled trial.

BACKGROUND: It is unknown which compounds in spermatozoa or seminal plasma may be involved in the regulation of sperm motility. OBJECTIVES: The aim of this study was to investigate the effects of DHA (22:6n-3), vitamin E, and their probable interactions in men with asthenozoospermia. METHODS: A factorial, randomized, double-blind, placebo-controlled trial was conducted in infertility clinics in Tehran, Iran. The participants were idiopathic asthenozoospermic men aged 20-45 y, with normal endocrine function. Their concentration of spermatozoa and percentage of morphologically normal spermatozoa were equal to or above the lower reference limits, according to the fifth edition of the WHO guideline. Out of 717 men referred to the infertility clinics, 180 asthenozoospermic men were randomly assigned to 1 of 4 groups according to stratified blocked randomization by age and sperm concentration. Participants took daily 465 mg DHA plus 600 IU vitamin E (DE), 465 mg DHA plus placebo (DP), 600 IU vitamin E plus placebo (EP), or both placebo capsules (PP) for 12 wk. Sperm characteristics, oxidative stress of seminal plasma, serum and sperm membrane fatty acids, dietary intakes, anthropometric measurements, and physical activity were measured at baseline and after 12 wk. RESULTS: After the intervention, mean ± SD sperm progressive motility was greater in the DE group (27.9 ± 2.8) than in the DP (25.7 ± 3.4), EP (26.1 ± 2.8), and PP (25.8 ± 2.6) groups (P < 0.05). Sperm count (P = 0.001) and concentration (P = 0.044) increased significantly in the DE group compared with the other 3 groups, whereas other semen parameters were not significantly different between the groups after the intervention. Serum concentrations of n-3 PUFAs were significantly higher in the DE and DP groups than in the EP and PP groups. CONCLUSIONS: Combined DHA and vitamin E supplements led to increased sperm motility; however, no significant changes occurred in sperm morphology and vitality in asthenozoospermic men.This trial was registered at clinicaltrials.gov as NCT01846325.

Reactive oxygen species and male reproductive hormones.

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility.

The Effects of Exposure to Low Frequency Electromagnetic Fields on Male Fertility.

CONTEXT: People are increasingly exposed to low frequency (LF) electromagnetic fields (EMFs), mainly from electricity distribution networks and electronic devices. Critics of this widespread exposure believe that it can have detrimental effects on the human body. On the other hand, many in vivo and in vitro studies have claimed that low frequency electromagnetic therapy can function as a form of alternative medicine and that therapists can treat disease by applying electromagnetic radiation or pulsed EMFs to the body or cells. It is not yet entirely clear, however, whether LF-EMF is beneficial or harmful. OBJECTIVES: This study aimed to examine the effects of LF-EMFs on men's reproductive functions, according to the types of waveform and the frequency and duration of exposure. DESIGN: The study reviewed all available research, both human and animal, on the effects of LF-EMFs on male reproductive functions, covering the literature from January 1978 to June 2016. The documents were obtained from PubMed, Science Direct, and Google Scholar, and any article that was irrelevant or a duplicate was excluded. A total of 61 articles were found, and 27 articles were reviewed. SETTING: This project was performed at the Avicenna Research Center (Tehran, Iran). PARTICIPANTS: Literature included human and animal studies conducted on rabbits, mice, rats, and boars. INTERVENTION: Among these studies, any article that was irrelevant, a duplicate, or published with duplicate data was excluded. At the end, 27 articles were checked. OUTCOME MEASURES: Outcome measures included testing related to reproductive organ weights, reproductive endocrinal hormones, fetal development, and spermatogenesis as well as sperm motility, morphology, and vitality. RESULTS: The reviewed studies provided contradictory results that were highly dependent on the exposure parameters, such as the shape and frequency of wave, intensity, duration, and timing of the exposure. CONCLUSIONS: LF-EMF at 15 Hz with a peak intensity of 8 Gauss, with a square waveform of 50 Hz frequency and a duration of a few hours or less can have a positive effect on sperm quality, motility, and fertility. Exposures at other frequencies either had no effects on the sperm's performance and quality or held biological hazard for cells. It appears that there is still little understanding of how EMF affects cellular functions. Therefore, more standardized and controlled studies should be carried out to understand the effects of EMF on the body.

Yoga Can Improve Assisted Reproduction Technology Outcomes in Couples With Infertility.

CONTEXT: Depending on the cause of the infertility, nonsurgical or surgical treatments may be used to treat men and women with infertility. Despite improved outcomes due to medical advances, assisted reproductive technology (ART) for couples with infertility is sometimes unsuccessful. Success may be affected by the patient's social, psychological, and physical status. OBJECTIVE: The study examined the effects of yoga-including asanas (yoga poses), pranayama (proper breathing), shavasana, and meditation-on male and female fertility and ART outcomes. DESIGN: The research team performed a literature review, electronically searching for articles published between January 1978 and January 2016 in the PubMed, Scopus, ScienceDirect, and Google Scholar databases. SETTING: The study took place at the Reproductive Biotechnology Research Center at the Avicenna Research Institute at the Academic Center for Education, Culture, and Research (Tehran, Iran). PARTICIPANTS: Participants were couples with infertility taking part in 87 reviewed studies. INTERVENTION: Yoga was the intervention. OUTCOME MEASURES: The outcome measures comprised fertility factors in males and females, fertility rate, and ART success rate. RESULTS: The reviewed studies showed that yoga can provide stress management for patients with infertility, with beneficial effects on fertility, helping couples give birth. They found that yoga also could reduce pain; decrease depression, anxiety, and stress; reduce the rate of assisted vaginal delivery; and improve fetal outcomes. CONCLUSIONS: Yoga can help couples overcome infertility and increase the ART success rate by improving the physiological and psychological states of both men and women.

Role of vitamin E and D3 supplementation in Intra-Cytoplasmic Sperm Injection outcomes of women with polycystic ovarian syndrome: A double blinded randomized placebo-controlled trial.

BACKGROUND & AIMS: Ovulation induction has been proven to impose oxidative stress during ICSI treatment cycle. Also, data indicates that PCOS women show higher oxidative markers. Available data are not convincing about which antioxidant supplements have the potential to overcome oxidative stress in PCOS subjects. The aim of this trial was to investigate the possible role of combined vitamin E and D supplementation in the ICSI outcomes (oocyte number and quality, embryo number and quality, pregnancy rate) of PCOS subjects. METHODS: A total of 105 PCOS infertile women scheduled for ICSI were enrolled in a double-blinded RCT to treatment group (vitamin E, 400 mg/day - and vitamin D3, 50,000 IU/one in two weeks, n = 52) or placebo group (n = 53) for 8 weeks. The primary outcomes were implantation rate, pregnancy and clinical pregnancy rate. Secondary outcomes included oocyte quality, embryo quality, fertilization rate, alteration in serum MDA, TAC and vitamin D3 after treatment. Further, association between serum and follicular fluid Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), and serum vitamin D3 level were assessed. RESULTS: Pregnancy, clinical pregnancy and implantation rate were significantly higher in treatment group (P < 0.001). Data analysis in both groups revealed a significant increase in serum MDA compared to baseline and a significant decrease in serum TAC compared to baseline after treatment. Further analysis showed that there is a positive weak association between vitamin D level, implantation rate (P = 0.015) and increased clinical pregnancy (P = 0.037). No significant association was detected between either follicular fluid or serum MDA and TAC and ICSI outcomes. CONCLUSIONS: In conclusion, the findings of this trial do not add clinical support to the evidence that vitamins E and D3 may play a role in the success rate of IVF via an antioxidant mechanism. REGISTRY CODE: IRCT2014081018662N1.

Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates.

INTRODUCTION: This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS: A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS: Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION: Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells.

BACKGROUND: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. OBJECTIVE: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. MATERIALS AND METHODS: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. RESULTS: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). CONCLUSION: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis.

Evaluation of an Aqueous-Ethanolic Extract from Rosmarinus officinalis (Rosemary) for its Activity on the Hormonal and Cellular Function of Testes in Adult Male Rat.

Rosmarinus officinalis has been used in traditional medicine extensively. This study evaluated the hormonal and cellular effects of Rosmarinus officinalis extract on testes of adult rats. Thirty male Wistar rats (in three groups) received 50 or 100 mg/Kg b.w of Rosmarinus officinalis extract (made from the plant's leaves, flower and stem) (treatment groups) and 10 mL/Kg b.w normal saline (control group) respectively, on a daily bases by gavage route for 60 days. Then, spermatological properties, histometric parameters and sperm dynamics, testis and body weight, testicular cell population and serum testosterone level were analyzed by an acceptable method. Results showed that the mean serum testosterone level was decreased significantly in both treatment groups (50 and 100 mg/Kg b.w) during the experiment time, compared with control group (p < 0.05). However, Rosmarinus officinalis did not change the total count, motility and viability of sperm. In addition, Rosmarinus officinalis at both doses did not change body and testes weight and their ratio. Furthermore, Rosmarinus officinalis increased the number of Spermatogonia at both doses, Spermatocyte at doses of 50 mg/Kg b.w, Leydig cell and Spermatid at dose of 100 mg/Kg b.w significantly (p < 0.05). Rosmarinus officinalis did not significantly affect the number of Spermatozoid and Sertoli cells. In conclusion, it seems that Rosmarinus officinalis may have some hormonal and cellular effects on the testes which can contribute the spermatogenesis process in rat. Rosmarinus officinalis may have antiandrogenic effect potentially indicating the possibility of developing herbal male contraceptive.

Propagation of human germ stem cells in long-term culture.

BACKGROUND: Spermatogonial stem cells (SSCs), a subset of undifferentiated type A spermatogonia, are the foundation of complex process of spermatogenesis and could be propagated in vitro culture conditions for long time for germ cell transplantation and fertility preservation. OBJECTIVE: The aim of this study was in vitro propagation of human spermatogonial stem cells (SSCs) and improvement of presence of human Germ Stem Cells (hGSCs) were assessed by specific markers POU domain, class 5, transcription factor 1 (POU5F1), also known as Octamer-binding transcription factor 4 (Oct-4) and PLZF (Promyelocytic leukaemia zinc finger protein). MATERIALS AND METHODS: Human testicular cells were isolated by enzymatic digestion (Collagenase IV and Trypsin). Germ cells were cultured in Stem-Pro 34 media supplemented by growth factors such as glial cell line-derived neurotrophic factor, basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor to support self-renewal divisions. Germline stem cell clusters were passaged and expanded every week. Immunofluorecent study was accomplished by Anti-Oct4 antibody through the culture. The spermatogonial stem cells genes expression, PLZF, was studied in testis tissue and germ stem cells entire the culture. RESULTS: hGSCs clusters from a brain dead patient developed in testicular cell culture and then cultured and propagated up to 6 weeks. During the culture Oct4 were a specific marker for identification of hGSCs in testis tissue. Expression of PLZF was applied on RNA level in germ stem cells. CONCLUSION: hGSCs indicated by SSCs specific marker can be cultured and propagated for long-term in vitro conditions. This article extracted from Ph.D. Thesis. (Zeinab Piravar).

The inductive effects of Centella asiatica on rat spermatogenic cell apoptosis in vivo.

Centella asiatica (L.) Urban has been traditionally used for the treatment of various disease and as a food for thousands of years in various parts of the world including eastern Asia, China and India. The goal of this study was to investigate the effects of Centella asiatica aqueous leaf extract on the induction of spermatogenic cell apoptosis in male rats. After lethal dose (LD(50)) assessment of plant extract, rats were divided in five groups. The experimental groups received orally 10, 50, 80 and 100 mg/kg aqueous leaf extract daily for 60 days and the control group received just water. After 60 days, body and testis weight were measured and blood samples were taken from the heart. To evaluate apoptosis and histological changes, tissue samples obtained from rat testes were stained by TUNEL assay and hematoxylin and eosin stain. Results showed that the sperm count, motility, and viability and the number of spermatogenic cells in the seminiferous tubules were significantly decreased compared with the control group. The number of apoptotic germ cells per seminiferous tubule cross-section was significantly increased in the experimental group (18.11 ± 3.5) compared with the control group (8.7 ± 0.81) (P < 0.05). Serum testosterone, follicle-stimulating hormone, and luteinizing hormone levels also showed significant decreases in the experimental groups (P < 0.05). There was also a significant decrease in testis weight in experimental groups compared with the control group (P < 0.05). It is concluded that Centella asiatica has toxicological effects on the reproductive system in male rats and, therefore, it is suggested that leaf extracts of Centella asiatica possess antifertility effects in the male rat.