Impact of melatonin administration on sperm quality, steroid hormone levels, and testicular blood flow parameters in small ruminants: A meta-analysis

Background and Aim: The impact of exogenous melatonin on the sperm quality of small ruminants is controversial. Therefore, this study aimed to synthesize previous findings on the influence of melatonin injection on sperm quality, steroid hormones, and testicular blood flow in small ruminants. Materials and Methods: Thirty studies were analyzed by computing the raw mean difference (RMD) as the effect size between the control and melatonin treatment groups, using the inverse of the variance for the random-effect model of the method of moments by DerSimonian and Laird. We assessed heterogeneity among studies using Q test. I2 statistic was used to classify the observed heterogeneity. We used Egger’s regression method to indicate publication bias. Results: Melatonin injection (p < 0.05) affected sperm concentration (RMD = 0.42 × 109/mL), morphology (RMD = 2.82%), viability (RMD = 2.83%), acrosome integrity (RMD = 4.26%), and DNA integrity (RMD = 1.09%). Total motility (RMD = 5.62%), progressive motility (RMD = 7.90%), acrosome integrity (RMD = 8.68%), and DNA integrity (RMD = 2.01%) of post-thawed semen in the melatonin-treated group were also increased (p < 0.05). Similarly, treatment with melatonin (p < 0.05) enhanced total motility (RMD = 5.78%), progressive motility (RMD = 5.28%), curvilinear velocity (RMD = 4.09 μm/s), straight-line velocity (RMD = 5.61 μm/s), and average path velocity (RMD = 4.94 μm/s). Testosterone (RMD = 1.02 ng/mL) and estradiol 17-ß levels (RMD = 0.84 pg/mL) were elevated (p < 0.05) in the melatonin-injected group. Melatonin implantation ameliorated testicular blood flow, as indicated by a significant reduction (p < 0.05) in the resistive index (RMD = 0.11) and pulsatility index (RMD = –0.15). Conclusion: Melatonin administration can increase the reproductive performance of small male ruminants

Carbon Monoxide modulation of neuronal differentiation

Several evidences support carbon monoxide (CO) for modulating cellular differentiation, in particular for neuronal cells. First, there are some reported studies documenting the biogenesis of mitochondria during spontaneous cell differentiation and it was demonstrated that CO promotes mitochondrial biogenesis. Secondly, ROS are signalling molecules in CO-induced pathways and are also key-players in neuronal differentiation. Third, CO has been described as anti-proliferative molecule in different cell types, namely smooth muscle, cancer and T cells, which can be involved in the balance between differentiation and proliferation that occurs during neurogenesis. Therefore, CO presents a strong potential for modulating neuronal differentiation, opening windows for the development of novel cell therapy strategies for neurological disorders.(...

The relationship between hypoxia, proliferation and apoptosis in murine CaNT tumours and human HT29 xenografts

Tumour hypoxia and cell proliferation are two factors which greatly influence cancer therapy. In this thesis the cell biology of tumours whose internal micro-environment was perturbed by therapeutically-relevant radiation doses or an oxygenation modifier (carbogen) was investigated. A well-defined murine experimental tumour, CaNT, and a widely used human tumour xenograft, HT29 were used in vivo and in vitro to study the relationship between hypoxia, proliferation and apoptosis. Hypoxia was assessed by measuring the incorporation of 7-(4'-(2-nitroimidazole-1-yl)-butyl)-theophylline (NITP), an immunologically identifiable hypoxia marker that binds bioreductively to cells under low-oxygen conditions. Experiments investigating the influence of various oxygen levels on NITP binding in separate phases of the cell cycle showed that aneuploid G2 cells disaggregated from CaNT tumours bind more NITP at all oxygen tensions than cells in other phases. The NITP binding in G1 and S phase cells was similar which could suggest that this phenomenon may be independent of cell size. HT29 xenografts showed a similar pattern of NITP binding, but with a lower overall nitroreductase activity compared with that seen in the murine tumours. CaNT and HT29 cells grown in vitro for several cell generations showed a different pattern of NITP binding. Simultaneous fluorescent staining of cells for hypoxia (NITP), proliferation (BrdUrd) and DNA content showed that treatment with a single fraction of carbogen induced a G2 phase delay in CaNT tumours. A 2-hour exposure of CaNT tumours to carbogen induced apoptosis, measured with the TdT assay, which could reflect re-perfusion injury to previously hypoxic cells. The experiments exploring the influence of carbogen breathing on proliferation in HT29 xenografts showed marked changes to the cell cycle. In HT29 xenografts carbogen treatment did not alter the cell cycle progression of oxic cells, whereas hypoxic cells completely halted progression through the cell cycle. The apoptotic response of CaNT and HT29 cell lines to radiation-induced DNA damage was investigated both in vivo and in vitro. CaNT and HT29 cell lines showed little or no radiation-induced apoptosis in vitro respectively. In contrast, in vivo doses as small as 0.5 Gy caused marked apoptosis. In CaNT tumours, the number of apoptotic cells increased from 10% in the controls to 33% 2 hours post treatment with 0.5 Gy. The percentage of apoptosis remained at an elevated level (22% even 24 hours after irradiation. HT29 xenografts treated with 0.5 and 5 Gy X-rays showed 24 and 26% apoptosis respectively. The influence of micro-environmental factors such as hypoxia, nutrient deprivation and cell density on the induction of apoptosis was tested in vitro. However none of these factors could explain the differences between the apoptotic response to ionising radiation in vivo and in vitro

Practical Clinical Andrology

This open access book offers a valuable resource for understanding the correct pathways in the context of sexual disorders, couple reproduction, gender identity dysphoria, conditions for which patients commonly ask for consultation and treatment. Based on clinical evidence, international guidelines and experts experience, practical clinical management strategies are presented for each condition. Each clinical care pathway is based on updated algorithm, level of evidence, photos and video-clips that describes the clinical presentations and the best practice management through diagnostic tools and medical or surgical treatment. Leading experts from the most important center of excellence in the field of sexual medicine joined to cover the field of andrology in its entirety, each of them dealing with a single topic from the top of their recognized experience and providing a complete and update textbook that will help urologists and other physicians in their daily clinical practice. This book is thought to be a practical and valuable reference for urologists, gynecologists, endocrinologists, psychiatrics and psychologists, and residents who are not specialty trained in andrology. It is designed for both young fellows training in different specialties and coming into contact with andrological issues for the first time and also more experienced clinicians and surgeons requiring updated guidelines and clear advice on the most controversial issues. This book will represent an invaluable quick consulting tool, updated in its scientific contents and rich in tables, images and video-clips

Practical Clinical Andrology

This open access book offers a valuable resource for understanding the correct pathways in the context of sexual disorders, couple reproduction, gender identity dysphoria, conditions for which patients commonly ask for consultation and treatment. Based on clinical evidence, international guidelines and experts experience, practical clinical management strategies are presented for each condition. Each clinical care pathway is based on updated algorithm, level of evidence, photos and video-clips that describes the clinical presentations and the best practice management through diagnostic tools and medical or surgical treatment. Leading experts from the most important center of excellence in the field of sexual medicine joined to cover the field of andrology in its entirety, each of them dealing with a single topic from the top of their recognized experience and providing a complete and update textbook that will help urologists and other physicians in their daily clinical practice. This book is thought to be a practical and valuable reference for urologists, gynecologists, endocrinologists, psychiatrics and psychologists, and residents who are not specialty trained in andrology. It is designed for both young fellows training in different specialties and coming into contact with andrological issues for the first time and also more experienced clinicians and surgeons requiring updated guidelines and clear advice on the most controversial issues. This book will represent an invaluable quick consulting tool, updated in its scientific contents and rich in tables, images and video-clips

Embryonic Stem Cells

Embryonic stem cells are one of the key building blocks of the emerging multidisciplinary field of regenerative medicine, and discoveries and new technology related to embryonic stem cells are being made at an ever increasing rate. This book provides a snapshot of some of the research occurring across a wide range of areas related to embryonic stem cells, including new methods, tools and technologies; new understandings about the molecular biology and pluripotency of these cells; as well as new uses for and sources of embryonic stem cells. The book will serve as a valuable resource for engineers, scientists, and clinicians as well as students in a wide range of disciplines

A longitudinal study of the experiences and psychological well-being of Indian surrogates

Study question: What is the psychological well-being of Indian surrogates during and after the surrogacy pregnancy? Summary answer: Surrogates were similar to a matched group of expectant mothers on anxiety and stress. However, they scored higher on depression during and after pregnancy. What is known already: The recent ban on trans-national commercial surrogacy in India has led to urgent policy discussions regarding surrogacy. Whilst previous studies have reported the motivations and experiences of Indian surrogates no studies have systematically examined the psychological well-being of Indian surrogates, especially from a longitudinal perspective. Previous research has shown that Indian surrogates are motivated by financial payment and may face criticism from their family and community due to negative social stigma attached to surrogacy. Indian surrogates often recruited by agencies and mainly live together in a “surrogacy house.” Study design, size, duration: A longitudinal study was conducted comparing surrogates to a matched group of expectant mothers over two time points: (a) during pregnancy (Phase1: 50 surrogates, 70 expectant mothers) and (b) 4–6 months after delivery (Phase 2: 45 surrogates, 49 expectant mothers). The Surrogates were recruited from a fertility clinic in Mumbai and the matched comparison group was recruited from four public hospitals in Mumbai and Delhi. Data collection was completed over 2 years. Participants/materials, setting, methods: Surrogates and expectant mothers were aged between 23 and 36 years. All participants were from a low socio-economic background and had left school before 12–13 years of age. In-depth faceto-face semi-structured interviews and a psychological questionnaire assessing anxiety, stress and depression were administered in Hindi to both groups. Interviews took place in a private setting. Audio recordings of surrogate interviews were later translated and transcribed into English. Main results and the role of chance: Stress and anxiety levels did not significantly differ between the two groups for both phases of the study. For depression, surrogates were found to be significantly more depressed than expectant mothers at phase 1 (p = 0.012) and phase 2 (p = 0.017). Within the surrogacy group, stress and depression did not change during and after pregnancy. However, a non-significant trend was found showing that anxiety decreased after delivery (p = 0.086). No participants reported being coerced into surrogacy, however nearly all kept it a secret from their wider family and community and hence did not face criticism. Surrogates lived at the surrogate house for different durations. During pregnancy, 66% (N = 33/50) reported their experiences of the surrogate house as positive, 24% (N = 12/50) as negative and 10% (N = 5/50) as neutral. After delivery, most surrogates (66%, N = 30/45) reported their experiences of surrogacy to be positive, with the remainder viewing it as neutral (28%) or negative (4%). In addition, most (66%, N = 30/45) reported that they had felt “socially supported and loved” during the surrogacy arrangement by friends in the surrogate hostel, clinic staff or family. Most surrogates did not meet the intending parents (49%, N = 22/45) or the resultant child (75%, N = 34/45). Limitations, reasons for caution: Since the surrogates were recruited from only one clinic, the findings may not be representative of all Indian surrogates. Some were lost to follow-up which may have produced sampling bias. Wider implications of the findings: This is the first study to examine the psychological well-being of surrogates in India. This research is of relevance to current policy discussions in India regarding legislation on surrogacy. Moreover, the findings are of relevance to clinicians, counselors and other professionals involved in surrogacy. Trial registration number: N/A

Washington University Senior Honor Thesis Abstracts (WUSHTA), Spring 2018

Complete issue of the Washington University Senior Honors Thesis Abstracts (WUSHTA), Spring 2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich Editor; Kristin G. Sobotka, Programs Manager; Jennifer Kohl

Artificial testis to study early gonadal development and germ cell differentiation

Studying the early germ cell development is of great significance, as germ cells transfer the genetic material between generations. However, in humans, this type of studies in vivo is not applicable, for obvious ethical reasons. Interestingly, differentiating human pluripotent stem cells (hPS cells) towards germ cells in vitro was recently reported. Therefore, studying differentiation of hPS cells towards germ cells is intriguing. On the other hand, due to the advancement in cancer therapy, the survival rates of the patients receiving chemotherapy and radiotherapy are improving dramatically. However, the improved survival rates increased the demand on fertility preservation, since most of the cancer treatments are gonadotoxic. In case of pubertal and post-pubertal male patients, semen cryopreservation offers a feasible and efficient option. Meanwhile, pre-pubertal patients do not have this option. Thus, finding an option for or such patients is absolutely encouraged. Hence, we aimed in this thesis at studying the early development and differentiation of the male germ cells in vitro, in order to find a robust protocol for fertility preservation for prepubertal male patients. Specifically, we investigated whether the culture conditions and gene expression profile could be used to predict the differentiation potential of human embryonic stem (hES) cells towards male germ cells, tried to optimize the culture conditions for rat germ cell differentiation using a three-dimensional (3D) culture system, investigated the possibility of differentiating rat germ cells in vitro from immature testicular tissue, and studied the effects of long term in vitro culture on testicular tissues from pre-pubertal patients. We have found that undifferentiated hES cell lines exhibit different gene expression profiles. Furthermore, the suspension culture method resulted in downregulation of the pluripotency markers NANOG and POU5F1, compared to the culture on feeders. In addition, BMP7 stimulation resulted in an upregulation in the germ cell markers KIT and DDX4 and somatic cell markers FSHR and HS3BD1. To study the optimal culture conditions for germ cell differentiation in vitro, rat testicular cells were cultured in a 3D culture system. We found that the choice of medium has an effect on Leydig cell functionality. In addition, the germ cells were migrating outwards the cell aggregations, making the conditions unfavorable for germ cell differentiation. Exploiting a reported method for murine germ cell differentiation in vitro to other species, we have obtained round spermatids expressing Crem and Acrosin (post- meiotic markers) from rat undifferentiated spermatogonia, using the organ culture system and MEMα medium + 10% KSR. Interestingly, when we cultured human pre-pubertal testicular tissue for long term in vitro using an organ culture system, we have found that the Leydig and Sertoli cells showed viability and functionality for up to 42 days and 21 days respectively. In conclusion, we have assessed the effect of culture conditions on the differentiation potential of hES cells towards male germ cells in vitro. We have also investigated the culture conditions suitable for rat germ cell differentiation in vitro using a 3D culture system or an organ culture setup. In addition, we have also studied the effect of long term culture of human prepubertal testicular tissue in vitro