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Ishimoto K.,Kyoto University | Gadelha H.,University of York | Gadelha H.,University of Birmingham | Gadelha H.,Center for Human Reproductive Science | And 5 more authors.
Physical Review Letters | Year: 2017

The flagellar beat is extracted from human sperm digital imaging microscopy and used to determine the flow around the cell and its trajectory, via boundary element simulation. Comparison of the predicted cell trajectory with observation demonstrates that simulation can predict fine-scale sperm dynamics at the qualitative level. The flow field is also observed to reduce to a time-dependent summation of regularized Stokes flow singularities, approximated at leading order by a blinking force triplet. Such regularized singularity decompositions may be used to upscale cell level detail into population models of human sperm motility. © 2017 American Physical Society.


Gaffney E.A.,University of Oxford | Gaffney E.A.,Center for Human Reproductive Science | Gadelha H.,University of Oxford | Gadelha H.,Center for Human Reproductive Science | And 8 more authors.
Annual Review of Fluid Mechanics | Year: 2011

Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.


Montenegro-Johnson T.D.,University of Birmingham | Montenegro-Johnson T.D.,Center for Human Reproductive Science | Smith D.J.,University of Birmingham | Smith D.J.,Center for Human Reproductive Science | And 2 more authors.
Physics of Fluids | Year: 2013

Shear-thinning is an important rheological property of many biological fluids, such as mucus, whereby the apparent viscosity of the fluid decreases with shear. Certain microscopic swimmers have been shown to progress more rapidly through shear-thinning fluids, but is this behavior generic to all microscopic swimmers, and what are the physics through which shear-thinning rheology affects a swimmer's propulsion? We examine swimmers employing prescribed stroke kinematics in two-dimensional, inertialess Carreau fluid: shear-thinning "generalized Stokes" flow. Swimmers are modeled, using the method of femlets, by a set of immersed, regularized forces. The equations governing the fluid dynamics are then discretized over a body-fitted mesh and solved with the finite element method. We analyze the locomotion of three distinct classes of microswimmer: (1) conceptual swimmers comprising sliding spheres employing both one- and two-dimensional strokes, (2) slip-velocity envelope models of ciliates commonly referred to as "squirmers," and (3) monoflagellate pushers, such as sperm. We find that morphologically identical swimmers with different strokes may swim either faster or slower in shear-thinning fluids than in Newtonian fluids. We explain this kinematic sensitivity by considering differences in the viscosity of the fluid surrounding propulsive and payload elements of the swimmer, and using this insight suggest two reciprocal sliding sphere swimmers which violate Purcell's Scallop theorem in shear-thinning fluids. We also show that an increased flow decay rate arising from shear-thinning rheology is associated with a reduction in the swimming speed of slip-velocity squirmers. For sperm-like swimmers, a gradient of thick to thin fluid along the flagellum alters the force it exerts upon the fluid, flattening trajectories and increasing instantaneous swimming speed. © Author(s) 2013.


Smith D.J.,University of Birmingham | Smith D.J.,University of Warwick | Smith D.J.,Center for Human Reproductive Science | Smith A.A.,University of Birmingham | And 3 more authors.
Journal of Engineering Mathematics | Year: 2011

Left-right symmetry breaking is critical to vertebrate embryonic development; in many species this process begins with cilia-driven flow in a structure termed the 'node'. Primary 'whirling' cilia, tilted towards the posterior, transport morphogen-containing vesicles towards the left, initiating left-right asymmetric development. Recent theoretical models based on the point-force stokeslet and point-torque rotlet singularities, explaining how rotation and surface-tilt produce directional flow are reviewed. Analysis of image-singularity systems enforcing the no-slip condition shows how tilted rotation produces a far-field 'stresslet' directional flow, and how time-dependent point-force and time-independent point-torque models are in this respect equivalent. Associated slender-body-theory analysis is reviewed; this approach enables efficient and accurate simulation of three-dimensional time-dependent flow, time-dependence being essential in predicting features of the flow such as chaotic advection, which have subsequently been determined experimentally. A new model for the nodal flow utilising the regularized stokeslet method is developed, to model the effect of the overlying Reichert's membrane. Velocity fields and particle paths within the enclosed domain are computed and compared with the flow profiles predicted by previous 'membrane-less' models. Computations confirm that the presence of the membrane produces flow-reversal in the upper region, but no continuous region of reverse flow close to the epithelium. The stresslet far-field is no longer evident in the membrane model, due to the depth of the cavity being of similar magnitude to the cilium length. Simulations predict that vesicles released within one cilium length of the epithelium are generally transported to the left via a 'loopy drift' motion, sometimes involving highly unpredictable detours around leftward cilia. Particles released just above the cilia tips were not predicted to reach to the extreme edges of the node, but rather are returned to the right by the counterflow. Flow to the right and left of the cilia array is of very small magnitude, suggesting that effective transport of particles to the extremities of the node requires cilia to be distributed all the way to the edges. There is no continuous layer of rightward flow close to the epithelium, except for a region close to the posterior edge of the node. Future work will involve investigating issues such as the precise shape of the node and cilia distribution and the effect of advection and diffusion on morphogens, hence explaining more fully the role of fluid mechanics in this vital developmental process. © 2010 Springer Science+Business Media B.V.


Curtis M.P.,University of Oxford | Curtis M.P.,Center for Human Reproductive Science | Kirkman-Brown J.C.,Center for Human Reproductive Science | Kirkman-Brown J.C.,University of Birmingham | And 4 more authors.
Journal of Theoretical Biology | Year: 2012

The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.


Gadelha H.,University of Oxford | Gadelha H.,Center for Human Reproductive Science | Gadelha H.,Capes Foundation | Gaffney E.A.,University of Oxford | And 5 more authors.
Journal of the Royal Society Interface | Year: 2010

Throughout biology, cells and organisms use flagella and cilia to propel fluid and achieve motility. The beating of these organelles, and the corresponding ability to sense, respond to and modulate this beat is central to many processes in health and disease. While the mechanics of flagellum-fluid interaction has been the subject of extensive mathematical studies, these models have been restricted to being geometrically linear or weakly nonlinear, despite the high curvatures observed physiologically. We study the effect of geometrical nonlinearity, focusing on the spermatozoon flagellum. For a wide range of physiologically relevant parameters, the nonlinear model predicts that flagellar compression by the internal forces initiates an effective buckling behaviour, leading to a symmetry-breaking bifurcation that causes profound and complicated changes in the waveform and swimming trajectory, as well as the breakdown of the linear theory. The emergent waveform also induces curved swimming in an otherwise symmetric system, with the swimming trajectory being sensitive to head shape - no signalling or asymmetric forces are required. We conclude that nonlinear models are essential in understanding the flagellar waveform in migratory human sperm; these models will also be invaluable in understanding motile flagella and cilia in other systems. © 2010 The Royal Society.


Sampaio P.,New University of Lisbon | Ferreira R.R.,New University of Lisbon | Guerrero A.,Instituto Gulbenkian Of Ciencia | Guerrero A.,National Autonomous University of Mexico | And 10 more authors.
Developmental Cell | Year: 2014

Internal organs are asymmetrically positioned inside the body. Embryonic motile cilia play an essential role in this process by generating a directional fluid flow inside the vertebrate left-right organizer. Detailed characterization of how fluid flow dynamics modulates laterality is lacking. We used zebrafish genetics to experimentally generate a range of flow dynamics. By following the development of each embryo, we show that fluid flow in the left-right organizer is asymmetric and provides a good predictor of organ laterality. This was tested in mosaic organizers composed of motile and immotile cilia generated by dnah7 knockdowns. In parallel, we used simulations of fluid dynamics to analyze our experimental data. These revealed that fluid flow generated by 30 or more cilia predicts 90% situs solitus, similar to experimental observations. We conclude that cilia number, dorsal anterior motile cilia clustering, and left flow are critical to situs solitus via robust asymmetric charon expression. © 2014 Elsevier Inc.


Purewal S.,Middlesex University | van den Akker O.,Middlesex University | van den Akker O.,Center for Human Reproductive science
Fertility and Sterility | Year: 2010

Objective: In 2007, the Human Fertilization and Embryology Authority permitted oocyte donation for research through voluntary donation or within an oocyte share model. The aims of this study were to investigate volunteer (nonpatient) women's attitudes and intentions to donate using components of the Theory of Planned Behavior and their attitudes toward parenthood through structural equation modeling. Design: Questionnaires. Setting: Online. Patient(s): A total of 253 nonpatient women. Main Outcome Measure(s): Attitudes towards oocyte donation for research and reasons for parenthood scale. Result(s): Of the 253 respondents, 94 were potential donors, 98 were possible donors, and 61 were non-donors. Most potential donors (68%) reported no preference towards donating their oocytes for research or an infertile couple. Structural equation modeling revealed that age (β = -.03) and components of the TPB (β = .16) had a statistically significant direct effect on intentions to donate for research. Attitudes toward parenthood was not linked to intentions to donate for research. Conclusion(s): There appears to be a strong altruistic motive along with the theoretical underpinnings of positive attitudes, feeling supported, and accepting the consequences of oocyte donation for research, suggesting these have the potential to inform recruitment practices and tailor clinical services. © 2010 American Society for Reproductive Medicine.


Van Den Akker O.B.A.,Middlesex University | Van Den Akker O.B.A.,Center for Human Reproductive science | Purewal S.,Middlesex University
Reproductive BioMedicine Online | Year: 2011

This study tested the effectiveness of the framing effect and fear appeals to inform young people about the risks of multiple births and the option of selecting elective single-embryo transfer (eSET). A non-patient student sample (age (mean ± SD) 23 ± 5.5 years; n = 321) were randomly allocated to one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: (3a) education and (3b) non-education. The primary outcome measure was the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed participants in the high fear, medium fear and gain condition demonstrated the most positive and significant differences (P < 0.001 to P < 0.05) in their knowledge, hypothetical intentions and modest changes in attitudes towards eSET than the low fear, loss frame and education and non-education messages. The results demonstrate that the use of complex persuasive communication techniques on a student population to promote immediate and hypothetical eSET preferences is more successful at promoting eSET than merely reporting educational content. Future research should investigate its application in a clinical population. A multiple pregnancy is a health risk to both infant and mother following IVF treatment. The aims of this study were to test the effectiveness of two persuasive communication techniques (the framing effect and fear appeals) to inform young people about the risks of multiple births and the hypothetical option of selecting elective single-embryo transfer (eSET) (i.e., only one embryo is transferred to the uterus using IVF treatment). A total of 321 non-patient student sample (mean age 23) were randomly allocated to read a message from one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: education (3a) and (3b) non-education. Participants completed the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed that participants in the high fear, medium fear and gain condition demonstrated the most positive and significant differences in their knowledge, hypothetical intentions and modest changes in attitudes towards eSET than the low fear, loss frame and education and non-education messages. This study recommends that health promotion based on the framing effect and fear appeals should be tested in clinical (patient) samples in the future. © 2011, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.


PubMed | St Georges Hospital, Fairfield General Hospital, Center for Human Reproductive Science and Royal Center for Defence Medicine
Type: | Journal: BMJ case reports | Year: 2015

In association with lower extremity amputation, complex genitourinary injuries have emerged as a specific challenge in modern military trauma surgery. Testicular injury or loss has profound implications for the recovering serviceman, in terms of hormone production and future fertility. The initial focus of treatment for patients with traumatic testicular loss is haemostasis, resuscitation and management of concurrent life-threatening injuries. Multiple reoperations are commonly required to control infection in combat wounds; in a review of 300 major lower extremity amputations, 53% of limbs required revisional surgery, with infection the commonest indication. Atypical infections, such as invasive fungal organisms, can also complicate military wounding. We report the case of a severely wounded serviceman with complete traumatic andropause, whose symptomatic temperature swings were initially mistaken for signs of occult sepsis.

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