Publications by authors named "Kevin Coward"

Sperm chromatin is distinct from somatic cell chromatin, as a result of extensive remodeling during the final stages of spermatogenesis. In this process, the majority of histones is replaced with protamines. The chromatin is consequently highly condensed and inert, which facilitates protection of the DNA.

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The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). The transcription factors TFAP2C and TEAD4 with activated RHOA accelerate embryo polarization. Here we show that these factors also accelerate the loss of totipotency.

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Nanoparticles and nanotechnology may present opportunities to revolutionize the prevention, treatment and diagnosis of a range of reproductive health conditions in women. These technologies are also used to improve outcomes of assisted reproductive technology. We highlight a range of these potential clinical uses of nanoparticles for polycystic ovary syndrome, endometriosis, uterine fibroids and sexually transmitted infections, considering and studies along with clinical trials.

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Fertility preservation in prepubertal boys with cancer requires the cryopreservation of immature testicular tissues (ITTs) prior to gonadotoxic treatment. However, the limited number of germ cells in small human ITT biopsies necessitates the development of anculture system for germ cell expansion using frozen-thawed ITTs. Here, we generated testicular organoids for themaintenance and expansion of gonocytes from frozen-thawed two-week-old neonatal bovine ITTs.

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The cryopreservation of immature testicular tissue (ITT) prior to gonadotoxic therapy is crucial for fertility preservation in prepubertal boys with cancer. However, the optimal holding time between tissue collection and cryopreservation has yet to be elucidated. Using the bovine model, we investigated four holding times (1, 6, 24, and 48 h) for ITTs before cryopreservation.

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Gonocytes play an important role in early development of spermatogonial stem cells and fertility preservation to acquire more high quality gonocytes in vitro for further germ cell-related research and applications, it is necessarily needed to enrich and in vitro propagate gonocytes from cryopreserved bovine testicular tissues. This study aimed to investigate the isolation, enrichment, and colony formation of gonocytes in vitro for germ cell expansion from cryopreserved neonatal bovine testicular tissues. The effects of several different in vitro culture conditions, including seeding density, temperature, serum replacement and extracellular matrices were investigated for the maintenance, proliferation and formation of gonocyte colonies in vitro.

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Background: It has long been thought that the factors affecting embryo and foetal development were exclusively maternally derived; hence, if issues regarding fertility and embryo development were to arise, the blame has traditionally been placed solely on the mother. An escalating interest in how paternal factors influence embryo development, however, has begun to prove otherwise. Evidence suggests that both seminal plasma (SP) and sperm contribute multiple factors that shape embryogenesis.

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Objective: To investigate the regulatory mechanisms and signaling molecules underlying hatching in mouse embryos.

Design: Experimental laboratory study using a mouse embryo model.

Setting: University-based basic scientific research laboratory.

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Objective: To investigate the impact of laser-assisted zona pellucida (ZP) drilling on the mouse embryo, with particular emphasis on molecular mechanisms, and the efficiency of embryo attachment capability using an in vitro model of implantation.

Design: Experimental study.

Setting: Academic research laboratory.

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At present, there is no standardised protocol for assisted hatching (AH) and the field is beset with contradictory data. We hypothesised that such contradiction may be related to inconsistencies in clinical practice. This study aimed to investigate the application, preferences, and variations of AH in current clinical practice prior to embryo transfer (AHpET) and biopsy (AHpBP).

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Article Synopsis
  • The study aims to create a core outcome set specifically for male infertility research to standardize data collection and enhance research quality.
  • Existing challenges in male infertility research include inconsistencies in outcome measures and lack of participant perspectives, which the new core set will address.
  • An international steering group will use systematic reviews and consensus methods, like the modified Delphi method, to gather input from various stakeholders and determine prioritized outcomes.
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Background: Oocyte activation deficiency (OAD) is attributed to the majority of cases underlying failure of ICSI cycles, the standard treatment for male factor infertility. Oocyte activation encompasses a series of concerted events, triggered by sperm-specific phospholipase C zeta (PLCζ), which elicits increases in free cytoplasmic calcium (Ca) in spatially and temporally specific oscillations. Defects in this specific pattern of Ca release are directly attributable to most cases of OAD.

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Article Synopsis
  • - ASPP2 plays a crucial role in maintaining the integrity of pseudostratified epithelia during development, particularly in the mouse E6.5 epiblast, where it prevents apical daughter cells from delaminating after cell division.
  • - The protein helps organize the filamentous actin cytoskeleton at apical junctions, essential for tissue integrity during critical morphogenetic events like gastrulation and in various embryonic regions.
  • - ASPP2's interaction with PP1 is vital for its tumor-suppressing function, highlighting its importance in tissues experiencing high mechanical stress, which could have implications for cancer research.
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Mouse zygote morphokinetics were measured during interphase, the mitotic period, cytokinesis, and two-cell stage. Sequences of rounder-distorted-rounder shapes were revealed, as were changing patterns of cross section area. A calcium chelator and an actin-disrupting agent inhibited the area changes that occurred between pronuclear envelope breakdown and cytokinesis.

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Phospholipase C zeta (PLCζ) is a sperm-specific protein that triggers oocyte activation. The analysis of PLCζ expression in human spermatozoa can be used as a diagnostic marker for oocyte activation deficiency. Our laboratory has previously optimized a standard "in-house" assay to determine PLCζ expression in human spermatozoa.

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Sperm-specific phospholipase C zeta (PLCζ) initiates intracellular calcium (Ca) transients which drive a series of concurrent events collectively termed oocyte activation. Numerous investigations have linked abrogation and absence/reduction of PLCζ with forms of male infertility in humans where oocyte activation fails. However, very few studies have examined potential relationships between PLCζ and advancing male age, both of which are increasingly considered to be major effectors of male fertility.

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Article Synopsis
  • - The study investigates how cells in developing embryos can determine their position and fate, focusing on the role of apicobasal polarity and the Hippo pathway during preimplantation development.
  • - Researchers analyzed the geometry and YAP (a Hippo pathway effector) localization in blastomeres from mouse and human embryos, finding a strong correlation between the amount of exposed cell surface area and YAP's presence in the nucleus.
  • - They developed hydrogel techniques to alter blastomere shape and discovered that during the compaction stage of early embryogenesis, cells start to sense geometric changes, potentially integrating signals to better understand their location within the embryo.
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To investigate exosomes as a noninvasive delivery tool for mammalian sperm. Exosomes were isolated from HEK293T cells and co-incubated with boar sperm .  Internalized exosomes were detected within 10 min of co-incubation.

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Objective: To investigate the applicability of phospholipase C zeta (PLCζ) analysis in assisting the clinical decision-making process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology.

Design: Fifty-six males (43 infertile/13 fertile) were screened using our PLCζ assay.

Setting: Fertility unit/university laboratory.

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To improve success rates, assisted reproductive technology (ART) procedures continually undergo optimization and enhancement such that the best quality gametes and embryos can be identified and manipulated, thus improving clinical outcomes. Laser technology is now being applied across ART to reduce procedure times and increase the consistency and reproducibility of traditional ART techniques such as assisted hatching, embryo biopsy, intracytoplasmic sperm injection cryopreservation and sperm immobilization/selection. This review examines the current status of cutting-edge laser-assisted reproductive technologies, investigates experimental techniques that are increasingly being applied clinically.

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State-of-the-art applications of nanomedicine have the potential to revolutionize the diagnosis, prevention, and treatment of a range of conditions and diseases affecting women's health. In this review, we provide a synopsis of potential applications of nanomedicine in some of the most dominant fields of women's health: mental health, sexual health, reproductive medicine, oncology, menopause-related conditions and dementia. We explore published studies arising from in vitro and in vivo experiments, and clinical trials where available, to reveal novel and highly promising therapeutic applications of nanomedicine in these fields.

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This chapter intends to summarise the importance of sperm- and oocyte-derived factors in the processes of sperm-oocyte binding and oocyte activation. First, we describe the initial interaction between sperm and the zona pellucida, with particular regard to acrosome exocytosis. We then describe how sperm and oocyte membranes fuse, with special reference to the discovery of the sperm protein IZUMO1 and its interaction with the oocyte membrane receptor JUNO.

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Nanoparticles have revolutionized medical research over the last decade. One notable emerging area of nanomedicine is research developments in the reproductive sciences. Since increasing evidence indicates links between abnormal gene expression and previously unexplained states of infertility, there is a strong impetus to develop tools, such as nanoparticle platforms, to elucidate the pathophysiological mechanisms underlying such states.

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Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm.

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Successful pregnancy is dependent upon the implantation of a competent embryo into a receptive endometrium. Despite major advancement in our understanding of reproductive medicine over the last few decades, implantation failure still occurs in both normal pregnancies and those created artificially by assisted reproductive technology (ART). Consequently, there is significant interest in elucidating the etiology of implantation failure.

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