Fatemeh Akyash

Bio: Fatemeh Akyash is an academic researcher from Shahid Sadoughi University of Medical Sciences and Health Services. The author has contributed to research in topics: Mesenchymal stem cell & Stem cell. The author has an hindex of 4, co-authored 15 publications receiving 176 citations.

Etiologies of sperm oxidative stress.

Abstract: Sperm is particularly susceptible to reactive oxygen species (ROS) during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN) leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions.

Pluripotency and differentiation of cells from human testicular sperm extraction: An investigation of cell stemness.

Abstract: Human male germ-line stem cells (hmGSCs) and human testis-derived embryonic stem cell-like (htESC-like) cells are claimed to be in vitro pluripotent counterparts of spermatogonial stem cells (SSCs), but the origin and pluripotency of human testis-derived cell cultures are still under debate. The aim of this study was to generate putative pluripotent stem cells in vitro from human testicular sperm-extracted (TESE) samples of infertile men, and to assess their pluripotency and capacity to differentiate. TESE samples were minced, enzymatically disaggregated and dispersed into single-cell or cluster suspensions, and then cultured. Initially, cell clusters resembled those described for hmGSCs and htESC-like cells, and were positive for markers such as OCT4/POU5F1, NANOG, and TRA-2-54. Prolonged propagation of cell clusters expressing pluripotency markers did not thrive; instead, the cells that emerged possessed characteristics of mesenchymal stromal cells (MSCs) such as STRO-1, CD105/EGLN1, CD13/ANPEP, SOX9, vimentin, and fibronectin. KIT, SOX2, and CD44 were not expressed by these MSCs. The multipotential differentiation capacity of these cells was confirmed using Oil Red-O and Alizarin Red staining after induction with specific culture conditions. It is therefore concluded that pluripotent stem cells could not be derived using the conditions previously reported to be successful for TESE samples.

Does Overnight Culture of Cleaved Embryos Improve Pregnancy Rate in Vitrified-Warmed Embryo Transfer Programme?

Abstract: Background Vitrification is a routine procedure in assisted reproductive technique (ART) lab. However, there is widespread variability between protocols of different centres. The aim of this study was to compare the chemical pregnancy, clinical pregnancy and live birth rates between one-day embryo culture and immediate transfer for frozen-thawed embryo transfer (FET) cycles. Methods In this cohort retrospective study, 366 FET cycles were divided into two groups: Group A, the embryos were warmed one day before transfer, and were cultured overnight; Group B, the embryos were warmed on the same day of transfer, at least were cultured 1 h before embryo transfer (ET). Chemical and clinical pregnancy and live birth rates were compared between two groups. Results The chemical pregnancy was higher in group A than B (37.9% versus 28.9%), but this difference was not significant (P = 0.07). Clinical pregnancy (30.8% versus 24.1%) and live birth (19.8% versus 22.05%) were similar in group A and B, (P = 0.15), and (P = 0.8). Conclusion: In conclusion, overnight culture and confirmation of mitosis resumption was not essential for FET cycles in vitrification method.

Effect of Human Testicular Cells Conditioned Medium on In Vitro Maturation and Morphology of Mouse Oocytes.

Abstract: Background: Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell developmentin vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growthdifferentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitoryfactor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM(hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes.Materials and Methods: In this experimental study, 360 germinal vesicle (GV) oocytes were obtained from NMRImice, aged 4-6 weeks that had received 5 IU pregnant mare's serum gonadotropin (PMSG) 48 hours before. GVoocytes were subjected to IVM. 120 GV oocytes were cultured in each medium; hTCCM as the test group, DMEM+ 20%FBS as the control group and Ham’s F10 + HFF medium as the sham group. The rates of the IVM and perivitellinespace (PVS) changes were recorded at 8, 16 and 24 hours after culture. The metaphase II (MII) oocytes weresubjected for in vitro fertilization (IVF) and the fertilization rate was evaluated after 1, 2, and 3 days.Results: There was a significant difference between the maturation rates in hTCCM (31.67% MII) and the control [0% MII,p 0.05). IVF success rate for MII oocytes obtained from IVM in the hTCCMgroup was 28.94% (n=11). Our data showed that hTCCM is an effective medium for GV oocyte growth and maturationcompared to the control medium.Conclusion: Our findings show that TCCM supports oocyte IVM in mice and affect oocyte morphology.

Characteristics of the human endometrial regeneration cells as a potential source for future stem cell-based therapies: A lab resources study

Abstract: Background: Human endometrium with consecutive regeneration capability undergoes monthly hormonal changes for probable implantation, which confirms the presence of the cells in the basalis layer known as stem cell. Objective: Previously, we reported the isolation and culture of the mesenchymal-like cells from human endometrium. In this study, we evaluated the biological and stemness characteristics of these cells. Materials and Methods: The characterization of Yazd human endometrialderived mesenchymal stem/stromal cells (YhEnMSCs) was assessed using immunofluorescence (IF) staining for CD105, VIMENTIN, and FIBRONECTIN as markers and RT-PCR for CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, MHCI, CD14, and MHCII genes. Flow cytometry (FACS) was performed for CD44, CD73, CD90, and CD105 markers. Moreover, the differentiation capacity of the YhEnMSCs to the osteoblast and adipocytes was confirmed by Alizarin Red and Oil Red staining. Results: YhEnMSCs expressed CD105, VIMENTIN, FIBRONECTIN, CD44, CD73, and CD90 markers and CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, and MHCI, but, did not express CD14, MHCII. Conclusion: Our data confirm previous reports by other groups indicating the application of endometrial cells as an available source of MSCs with self-renewal and differentiation capacity. Accordingly, YhEnMSCs can be used as a suitable source for cell-based therapies. Key words: Cell-based therapy, Endometrium, Mesenchymal stem/stromal cells, Regenerative medicine, Stem cells, Uterus.

Oxidative stress and sperm function: A systematic review on evaluation and management

Abstract: Objective: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction. Methods: The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were used to search PubMed, Medline, EMBASE, and the Cochrane electronic databases for studies investigating the role of oxidative stress (OS) on sperm function. Results: The literature search yielded 1857 studies, of which 1791 articles were excluded because of irrelevance of data, non-English language, non-human nature or because they were case reports or commentaries. All included studies were reviews (46), meta-analyses (one), original research studies (18) and guideline articles (one). The studies were published between 1984 and 2018. Under normal physiological conditions, ROS are vital for sperm maturation, hyperactivation, capacitation, acrosome reaction, as well as fertilisation. However, a number of endogenous and exogenous causes may induce supra-physiological levels of ROS resulting in lipid peroxidation, sperm DNA fragmentation and apoptosis, and consequently infertility. Several laboratory testing methods can be used in infertile men to diagnose OS. Treatment usually involves antioxidant supplementation and, when possible, elimination of the causative factor. Conclusion: OS is an important cause of male factor infertility. Its assessment provides essential information that can guide treatment strategies aimed at improving the male's reproductive potential. Abbreviations: bp: base-pair; CAT: catalase; LPO: lipid peroxidation; MDA: malondialdehyde; MiOXSYS: Male Infertility Oxidative System; mtDNA: mitochondrial DNA; NAD(PH): nicotinamide adenine dinucleotide (phosphate); NO: nitric oxide; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ORP: oxidation-reduction potential; OS: oxidative stress; PKA: protein kinase A; PLA2: phospholipase A2; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA: poly-unsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBA: thiobarbituric acid.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

Abstract: Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

Role of oxidative stress, infection and inflammation in male infertility.

Abstract: Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation-mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.

Human embryonic stem cell lines derived from single blastomeres

Abstract: At present it is necessary to destroy embryos ex utero to obtain human embryonic stem (hES) cells, but a study in mice suggests that ES cells might be generated using a single-cell biopsy technique similar to that used for preimplantation genetic diagnosis (PGD). This will not interfere with the developmental potential of the embryo. Overnight growth of a single blastomere could yield cells that may be used for both genetic testing and stem cell production without altering the clinical outcome. The investigators carried out ten experiments which, collectively, showed that hES cells can be derived from single blastomeres. Starting with unused embryos produced by in vitro fertilization, 19 ES-cell-like outgrowths and two stable hES cell lines were obtained. A majority of isolated blastomeres divided at least once, and about half formed vesicles or clumps that produced outgrowths within 2 days. The cells remained able to form derivatives of all three embryonic germ layers (primitive endoderm, mesoderm, ectoderm) in vitro and also in teratomas. Among the outcomes observed over several days were three that are typical when ES cells are derived from human embryos. Cells resembling trophectoderm dominated some cultures. Secondly, cells that initially resembled ES cells differentiated within cultures. Finally, ES-cell-like cells continued to proliferate without differentiating. Some hES cell lines proliferated without differentiating for longer than 8 months. Both karyotypes and the expression of markers of pluripotency were normal. The ability to create new stem cell lines without destroying embryos addresses the ethical concerns shared by many interested individuals. Potentially, matched tissues can be generated for children and siblings born from transferred PGD embryos. Further studies will be needed to learn whether blastomere-derived hES cell lines resemble conventional hES cell lines in their ability to form functional differentiated cell types. The investigators recommend that, until safety issues are resolved, this procedure be used only in the context of PGD.