Academic Unit of Reproductive and Developmental Medicine

Sheffield, United Kingdom

Academic Unit of Reproductive and Developmental Medicine

Sheffield, United Kingdom
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News Article | May 25, 2017
Site: www.sciencedaily.com

Scientists at the University of Sheffield have developed a new technique to examine human sperm without killing them -- helping to improve the diagnosis of fertility problems. The Magnetic Resonance Spectroscopy technique, uses powerful magnets and works like radar by firing pulses of energy at the sperm sample inside a purpose built scanner and then listening to the echoed signal by the molecules in response. This could help to distinguish between populations of good or poor sperm. Unlike other more destructive examination methods, the low energy pulses do not damage sperm, meaning they could potentially go on to be used in IVF treatment. This is similar to a technique that doctors use to capture images of cells and tissues inside the body. The novel approach was pioneered by physicists from the University of Sheffield's Academic Unit of Radiology working together with fertility experts from the University's Academic Unit of Reproductive and Developmental Medicine in the interdisciplinary spermNMR project. Professor Martyn Paley, from the University's Department of Infection, Immunity and Cardiovascular Disease, said: "The technique of Magnetic Resonance Spectroscopy has been previously used to examine the molecular composition of many cells and tissues in other diseases such as cancer, but it has never previously been used to examine live sperm. As such, these results are a world first." During the study, scientists examined fresh sperm samples from healthy volunteers and patients for just over an hour. From the data gathered scientists were able to build up a profile of the molecules present in the sperm and how they differ between samples. Professor Allan Pacey, fertility expert from the University of Sheffield, who was part of the spermNMR study team, said: "Most of the advanced techniques we have available to examine the molecules in sperm end up destroying them in the process by either adding stains or by breaking open their membranes to look at the contents. "To potentially have a technique which can examine the molecular structure of sperm without damaging them is really exciting." One of the technical challenges that the team faced was how to detect the molecules that were present in sperm rather than those present in semen, the fluid in which sperm are ejaculated. To do this, the team examined a number of 'sperm washing' techniques that are currently used to prepare sperm for IVF. They found that by spinning the samples very fast in a centrifuge several times they were able to reduce the background noise from molecules in semen to a point where they could reliably detect the ones from sperm. Research Associate Dr Sarah Calvert from the spermNMR team, said: "Washing the sperm in a centrifuge is a critical step for this technique to work as any contamination from seminal plasma can also be detected by the scanner. But by adding an extra spin cycle to the techiques that are commonly used in IVF we were able to minimize that contamination." The results of the study show that a number of molecules such as Choline (vitamin-like essential nutrient) and Glycerophosphocholine (a natural choline compound found in the brain), Lipids (common components of sperm cell membranes) and Lactate (an end product of cellular energy usage) were significantly different between samples of sperm separated into 'good' and 'poor' populations. Research Fellow Dr Steven Reynolds explained: "The fact we can detect differences in molecular composition between samples of 'good' and 'poor' sperm is really significant because it opens up the opportunity for us to develop a novel biomarker to help with diagnosis. "Or it might one day allow us to design specific therapies for men with poor sperm that might help give them a boost."


News Article | May 24, 2017
Site: www.eurekalert.org

Scientists at the University of Sheffield have developed a new technique to examine human sperm without killing them -- helping to improve the diagnosis of fertility problems. The Magnetic Resonance Spectroscopy technique, uses powerful magnets and works like radar by firing pulses of energy at the sperm sample inside a purpose built scanner and then listening to the echoed signal by the molecules in response. This could help to distinguish between populations of good or poor sperm. Unlike other more destructive examination methods, the low energy pulses do not damage sperm, meaning they could potentially go on to be used in IVF treatment. This is similar to a technique that doctors use to capture images of cells and tissues inside the body. The novel approach was pioneered by physicists from the University of Sheffield's Academic Unit of Radiology working together with fertility experts from the University's Academic Unit of Reproductive and Developmental Medicine in the interdisciplinary spermNMR project. Professor Martyn Paley, from the University's Department of Infection, Immunity and Cardiovascular Disease, said: "The technique of Magnetic Resonance Spectroscopy has been previously used to examine the molecular composition of many cells and tissues in other diseases such as cancer, but it has never previously been used to examine live sperm. As such, these results are a world first." During the study, scientists examined fresh sperm samples from healthy volunteers and patients for just over an hour. From the data gathered scientists were able to build up a profile of the molecules present in the sperm and how they differ between samples. Professor Allan Pacey, fertility expert from the University of Sheffield, who was part of the spermNMR study team, said: "Most of the advanced techniques we have available to examine the molecules in sperm end up destroying them in the process by either adding stains or by breaking open their membranes to look at the contents. "To potentially have a technique which can examine the molecular structure of sperm without damaging them is really exciting." One of the technical challenges that the team faced was how to detect the molecules that were present in sperm rather than those present in semen, the fluid in which sperm are ejaculated. To do this, the team examined a number of 'sperm washing' techniques that are currently used to prepare sperm for IVF. They found that by spinning the samples very fast in a centrifuge several times they were able to reduce the background noise from molecules in semen to a point where they could reliably detect the ones from sperm. Research Associate Dr Sarah Calvert from the spermNMR team, said: "Washing the sperm in a centrifuge is a critical step for this technique to work as any contamination from seminal plasma can also be detected by the scanner. But by adding an extra spin cycle to the techiques that are commonly used in IVF we were able to minimize that contamination." The results of the study show that a number of molecules such as Choline (vitamin-like essential nutrient) and Glycerophosphocholine (a natural choline compound found in the brain), Lipids (common components of sperm cell membranes) and Lactate (an end product of cellular energy usage) were significantly different between samples of sperm separated into 'good' and 'poor' populations. Research Fellow Dr Steven Reynolds explained: "The fact we can detect differences in molecular composition between samples of 'good' and 'poor' sperm is really significant because it opens up the opportunity for us to develop a novel biomarker to help with diagnosis. "Or it might one day allow us to design specific therapies for men with poor sperm that might help give them a boost." The study is published today (24 May 2017) in the journal Molecular Human Reproduction and was funded by an Medical Research Council grant "Spectroscopic Probes Of Energy Regulation And Metabolism (SPERM): Using High-Resolution Magnetic Resonance Spectroscopy Of Metabolic Pathways To Identify Potential Biomarkers Of Male Fertility" (Grant Ref MR/M010473/1) awarded to Professors Allan Pacey and Martyn Paley. For further information please contact: Amy Pullan, Media Relations Officer, University of Sheffield, 0114 222 9859, a.l.pullan@sheffield.ac.uk The paper, '1H Magnetic Resonance Spectroscopy of live human sperm' by Reynolds et al, will be published in the journal Molecular Human Reproduction, at 00:01 (BST) on 24 May 2017 More details about the project can be found on the study website at: http://spermnmr. The twitter account for the project is: @SpermNMR With almost 27,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world's leading universities. A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines. Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in. Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2017 and was voted number one university in the UK for Student Satisfaction by Times Higher Education in 2014. In the last decade it has won four Queen's Anniversary Prizes in recognition of the outstanding contribution to the United Kingdom's intellectual, economic, cultural and social life. Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields. Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations. For further information, please visit http://www. To read other news releases about the University of Sheffield, visit http://www.


Holt W.V.,Academic Unit of Reproductive and Developmental Medicine | Del Valle I.,Academic Unit of Reproductive and Developmental Medicine | Fazeli A.,Academic Unit of Reproductive and Developmental Medicine
Theriogenology | Year: 2015

Heat shock protein A8 (HSPA8) is a highly conserved member of the Hsp70 family, which is expressed in oviductal cells, translocated into oviductal fluid, and becomes attached to the sperm surface during sperm transport. Previous research has shown that HSPA8 supports mammalian sperm viability during in vitro incubation at both 5 °C and body temperature. The present series of experiments was designed to explore the possibility that bovine recombinant HSPA8 might therefore protect bull spermatozoa during cryopreservation through its beneficial effects on the sperm plasma membrane. Soy-based cryopreservation media were used in these experiments. The effects of HSPA8 addition before freezing were examined at concentrations ranging from 0.2 to 6.4 μg/mL, whereas the effects of postthaw HSPA8 addition were tested between 0.2 and 12.8 μg/mL. When bull spermatozoa (from beef and dairy breeds) were frozen in the presence of HSPA8, beneficial but complex effects on postthaw viability were observed. Low HSPA8 concentrations (0.2 and 0.4 μg/mL) resulted in significantly reduced postthaw sperm viability, but concentrations above 0.8 μg/mL improved plasma membrane integrity. If HSPA8 was added to spermatozoa after thawing, outcomes were also biphasic and beneficial effects on viability were only seen if the HSPA8 concentration exceeded 3.2 μg/mL. Beneficial effects were significantly more apparent with beef rather than dairy breeds. When HSPA8 was used in combination with cholesterol-loaded cyclodextrin, spermatozoa from the beef breeds showed significantly lower apoptotic effects. This was not observed with the dairy breeds. © 2015 Elsevier Inc..


Holt W.V.,Academic Unit of Reproductive and Developmental Medicine | Fazeli A.,Academic Unit of Reproductive and Developmental Medicine
Theriogenology | Year: 2016

Research over the past 3 decades has caused a major shift in the way that the oviduct, or fallopian tube, is perceived. Previously, it was regarded as little more than the anatomic site for fertilization, where spermatozoa and oocytes meet as they travel in opposite directions. However, this view has been radically altered by the realization that both spermatozoa and oocytes elicit changes in the biochemical composition of oviductal fluid through the induction of novel gene expression. Moreover, it has also been shown that only a privileged sperm population, selected on the basis of multiple criteria, is permitted to enter the oviduct, where they are subjected to even more selection processes that control their motility and capacitation status, thus either inhibiting or facilitating their progress toward the oocyte. Even more recently, it has become apparent that the oviduct has some ability to differentiate the genetic signatures of X- and Y-bearing spermatozoa. Although how exactly this is achieved is unknown, it prompts us to speculate that the oviduct may also be capable of distinguishing other genetically encoded properties of individual spermatozoa and that there must ultimately be a huge payoff in terms of selective animal breeding. © 2016 Elsevier Inc.


Kapaya H.,Academic Unit of Reproductive and Developmental Medicine | Broughton-Pipkin F.,University of Nottingham | Hayes-Gill B.,University of Nottingham | Loughna P.V.,University of Nottingham
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2015

Objectives: To investigate effects of maternal smoking on the fetal heart rate (FHR) in ambulatory patients using a portable fetal electrocardiogram recording device. Methods: A prospective cohort study of 43 pregnant smokers and 43 non-smoking gestation-matched controls with uncomplicated singleton pregnancies. Smokers were divided into light (1-10) and moderate (11-20 cigarettes/d). The FHR was recorded for 16 h with smokers smoking at will, using an event button to record when they lit a cigarette. Fifty recordings were made in the patients' homes with 36 in ambulatory inpatients. Three consecutive 30-min epochs (before, during and after smoking) were compared with the controls. Results: Basal FHR was significantly lower before smoking in the foetuses of smokers compared with non-smokers (p = 0.048). During smoking, there was a significant dose-dependent fall in short-, long-term and true beat-to-beat variabilities (p = 0.004, p < 0.0001 and p = 0.024, respectively). Conclusion: Maternal smoking leads to reversible changes in FHR variability that mimic those associated with an increased incidence of adverse cardiovascular events in adults. As heart rate and variability reflect the autonomic control of the heart, our findings suggest that maternal smoking interferes with the autonomic control of the FHR. © 2014 Informa UK Ltd. All rights reserved.


Whitby E.,Academic Unit of Reproductive and Developmental Medicine | Wright P.,Royal Hallamshire Hospital
Seminars in Fetal and Neonatal Medicine | Year: 2015

Fetal magnetic resonance imaging (MRI) is currently offered in a limited number of centers but is predominantly used for suspected fetal central nervous system abnormalities. This article concentrates on the role of the different imaging sequences and their value to clinical practice. It also discusses the future of fetal MRI. © 2015.


Pacey A.A.,Academic Unit of Reproductive and Developmental Medicine
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2012

The assessment of male infertility is largely based around the examination of a freshly produced ejaculate by a trained technician according to laboratory methods agreed by the World Health Organization. Although many suggestions have been made to improve this approach, the basic techniques of semen analysis established in the 1950s are still being used. Although several putative tests of sperm function have been developed (e.g. the measurement of sperm hyperactivation, sperm acrosomal status, or sperm penetration through mucus or binding to zona pellucida), none have made it into routine clinical practice. Recently, several 'new' tests of sperm function and sperm selection have been developed. These include the use of microfluidic chambers, electrophoresis, the binding of sperm to hyaluronic acid, and high magnification sperm selection. Randomised-controlled trials are needed to evaluate these as a replacement or addition to routine semen analysis or current sperm preparation methods. © 2012 Elsevier Ltd. All rights reserved.


PubMed | Academic Unit of Reproductive and Developmental Medicine
Type: Journal Article | Journal: Theriogenology | Year: 2015

Research over the past 3 decades has caused a major shift in the way that the oviduct, or fallopian tube, is perceived. Previously, it was regarded as little more than the anatomic site for fertilization, where spermatozoa and oocytes meet as they travel in opposite directions. However, this view has been radically altered by the realization that both spermatozoa and oocytes elicit changes in the biochemical composition of oviductal fluid through the induction of novel gene expression. Moreover, it has also been shown that only a privileged sperm population, selected on the basis of multiple criteria, is permitted to enter the oviduct, where they are subjected to even more selection processes that control their motility and capacitation status, thus either inhibiting or facilitating their progress toward the oocyte. Even more recently, it has become apparent that the oviduct has some ability to differentiate the genetic signatures of X- and Y-bearing spermatozoa. Although how exactly this is achieved is unknown, it prompts us to speculate that the oviduct may also be capable of distinguishing other genetically encoded properties of individual spermatozoa and that there must ultimately be a huge payoff in terms of selective animal breeding.


PubMed | Academic Unit of Reproductive and Developmental Medicine
Type: Journal Article | Journal: Theriogenology | Year: 2015

Heat shock protein A8 (HSPA8) is a highly conserved member of the Hsp70 family, which is expressed in oviductal cells, translocated into oviductal fluid, and becomes attached to the sperm surface during sperm transport. Previous research has shown that HSPA8 supports mammalian sperm viability during in vitro incubation at both 5 C and body temperature. The present series of experiments was designed to explore the possibility that bovine recombinant HSPA8 might therefore protect bull spermatozoa during cryopreservation through its beneficial effects on the sperm plasma membrane. Soy-based cryopreservation media were used in these experiments. The effects of HSPA8 addition before freezing were examined at concentrations ranging from 0.2 to 6.4 g/mL, whereas the effects of postthaw HSPA8 addition were tested between 0.2 and 12.8 g/mL. When bull spermatozoa (from beef and dairy breeds) were frozen in the presence of HSPA8, beneficial but complex effects on postthaw viability were observed. Low HSPA8 concentrations (0.2 and 0.4 g/mL) resulted in significantly reduced postthaw sperm viability, but concentrations above 0.8 g/mL improved plasma membrane integrity. If HSPA8 was added to spermatozoa after thawing, outcomes were also biphasic and beneficial effects on viability were only seen if the HSPA8 concentration exceeded 3.2 g/mL. Beneficial effects were significantly more apparent with beef rather than dairy breeds. When HSPA8 was used in combination with cholesterol-loaded cyclodextrin, spermatozoa from the beef breeds showed significantly lower apoptotic effects. This was not observed with the dairy breeds.


PubMed | Royal Hallamshire Hospital and Academic Unit of Reproductive and Developmental Medicine
Type: Journal Article | Journal: Seminars in fetal & neonatal medicine | Year: 2015

Fetal magnetic resonance imaging (MRI) is currently offered in a limited number of centers but is predominantly used for suspected fetal central nervous system abnormalities. This article concentrates on the role of the different imaging sequences and their value to clinical practice. It also discusses the future of fetal MRI.

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