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Martin H Johnson

Publications and source records attributed to Martin H Johnson.

14 recordsLinked to original sources
PubMed2006

Escaping the tyranny of the embryo? A new approach to ART regulation based on UK and Australian experiences.

The early legislative responses to fertilization of human oocytes in vitro exaggerated the protection of the embryo at the expense of the interests of other parties. Although more recent legislative changes have lessened this embryonic grip, it nonetheless still distorts legal thinking and is fundamentally in conflict with biological understanding. Drawing largely on experiences in the UK and Australia, a proposal is explored that reframes the legislative approach to the regulation of assisted reproductive technology (ART) with the following objectives: (i) to align more closely the legal and biological understandings of the earliest stages of human development; (ii) to place the legislative focus on objective, intent and outcome; and in the process (iii) to disentangle legally and conceptually the status of the embryo from that of the potential child. Experiences in the UK and Australia are drawn on, because these two jurisdictions have a common legal heritage and were among the earliest players both scientifically and legally but have pursued very different legal routes to their current legislative practices.

Australia↗
PubMed2006

Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes.

BACKGROUND: The molecular basis of changes underlying the altered sensitivity of the uterine luminal epithelium (LE) to the embryo over the peri-implantation period is not fully understood. METHODS: Microarray analysis was performed on purified LE isolated from the pseudo-pregnant mouse uterus at 12-h intervals from pre-receptivity through the implantation window to refractoriness. The aim was to identify genes whose expression changes in the LE during this period. RESULTS: A total of 447 transcripts were identified whose abundance changed more than 2-fold in the LE but which did not change in the underlying stroma (S) and glands. Six major patterns of changing expression were noted. Of the 447 genes, 140 were expressed in LE at least 15-fold higher than in S and glandular epithelium (GE) (101 of these more than 20-fold). Detailed spatiotemporal expression profiles were derived for several genes previously implicated in implantation (including Edg7, Ptgs1, Pla2g4a and Alox15). CONCLUSIONS: Functional changes in LE receptivity are characterized by changing constellations of gene expression. Pre-receptivity has a different molecular footprint to refractoriness. Because we have used the pseudo-pregnant mouse model, these changes are driven solely by endocrine signals rather than events downstream of embryo attachment. Some of these genes have been described in previous microarray studies on endometrium, but for the majority, this is the first time they have been implicated in implantation. The 140 genes enriched in the LE greatly expand the list of epithelial markers and provide many novel candidates for further studies to identify genes playing important roles in receptivity and embryo attachment.

Animals↗
PubMed2006

Trophoblast and hypoblast in the monotreme, marsupial and eutherian mammal: evolution and origins.

The pregastrula stage mammalian conceptus consists of both embryonic and non-embryonic components. The latter forms the bulk of the tissues, provides nutrition for the developing embryo and also contributes developmental signals that influence events within the embryo itself. Understanding the origins and relationships between the embryonic and extraembryonic cell lineages is thus central to understanding development in mammals. Despite the apparent gross differences in early developmental strategy and form, the conceptuses of eutherian, marsupial and monotreme mammals show some remarkable similarities in the lineage allocation to trophoblast and hypoblast and in the emergent properties of the two cell types. We suggest that the gross differences can be explained by two relatively small evolutionary timing changes affecting cell adhesion patterns and the polarisation of developmentally significant information. These changes result in the conversion of a unilaminar blastocyst to a morula form composed of blastomeres with increased regulatory capacity.

Animals↗
PubMed2005

Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception.

Activation of the receptors for leukemia inhibitory factor (LIF) and IL-11 is essential for embryo attachment and decidualization in mice. Both receptors induce activation of the Stat family of signal transducers via the Jak/Stat pathway. Here, we aimed to establish whether activation of Stat3 in maternal endometrium is essential for successful implantation. Functional blockade of Stat3 before implantation, by injection into the uterine lumen of a cell-permeable Stat3 peptide inhibitor, reduced embryo implantation specifically by 70% (P < 0.001). Stat3 is phosphorylated in the luminal epithelium (LE) in response to LIF, and this phosphorylation was significantly reduced both in vitro and in vivo by the Stat3 inhibitor. The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation. Successful implantation is therefore dependent on phosphorylation and activation of Stat3 in the endometrium before implantation. This finding provides a target for contraceptive development, based on selective blockade of signal transduction pathways essential for implantation. This study demonstrates that cell-permeable peptide inhibitors can be used effectively to target intracellular signaling pathways in the uterine LE.

Animals↗
PubMed2005

Developing essential professional skills: a framework for teaching and learning about feedback.

BACKGROUND: The ability to give and receive feedback effectively is a key skill for doctors, aids learning between all levels of the medical hierarchy, and provides a basis for reflective practice and life-long learning. How best to teach this skill? DISCUSSION: We suggest that a single "teaching the skill of feedback" session provides superficial and ineffective learning in a medical culture that often uses feedback skills poorly or discourages feedback. Our experience suggests that both the skill and the underlying attitude informing its application must be addressed, and is best done so longitudinally and reiteratively using different forms of feedback delivery. These feedback learning opportunities include written and oral, peer to peer and cross-hierarchy, public and private, thereby addressing different cognitive processes and attitudinal difficulties. SUMMARY: We conclude by asking whether it is possible to build a consensus approach to a framework for teaching and learning feedback skills?

Assertiveness↗
PubMed2005

The problematic in-vitro embryo in the age of epigenetics.

During use of many assisted reproductive technologies, the embryo spends time in vitro. The immediate and long-term epigenetic impacts of this exposure to an in-vitro environment are discussed in the context of the health of the offspring. Three exemplary types of possible epigenetic impact are discussed: embryonic cell numbers, mitochondria, and genomic imprints. There is evidence that all of these can be affected in the short term and that these short-term impacts can have heritable consequences across developmental cell generations into maturity. There is also evidence of association between the observed impact and pathology, but as yet no unequivocal evidence of causality for humans and mice. The problematic in-vitro embryo is considered paradigmatic for a central question facing biology: how does the environment interact epigenetically with the genome to produce variable phenotypic outcomes?

Adaptation, Biological↗
PubMed2004

A preliminary study on the use of experiential learning to support women's choices about infant feeding.

OBJECTIVE: To assess the impact of experiential learning methodologies in primiparous women on their choice and maintenance of an infant feeding method. STUDY DESIGN: A prospective controlled study into experiential learning methods applied to patients with four months' follow up. Seventy-three primiparous women attending the antenatal clinic at the West Suffolk Hospital for their 32 weeks check were allocated to two groups on the basis of date of attendance. Multiple pregnancy and serious illness were excluded. Thirty-three women attended a two hour seminar on breast feeding using experiential techniques. Forty had routine antenatal care and acted as controls. Breast feeding rates of the two groups were recorded at various stages. Assessment also included comments from questionnaires. RESULTS: The two groups did not differ significantly in the number of women proposing to breast feed their infants (Z = -0.0490, P = 0.9609) nor in the numbers of women breast feeding on day one ( Z = -0.6203, P = 0.5350). There were proportionally more women breast feeding their infants at two weeks ( Z = -1.4944, P = 0.1351) in the subject group, but this was not statistically significant. However, the difference at four months was significant, ( Z = -2.5784, P = 0.0099), more than double the percentage of controls maintaining some breast feeding to four months in the subject group. CONCLUSIONS: Experiential learning was associated with increased rates of prolonged breast feeding, possibly due to increased patient confidence in their choice. This learning approach could be applied to other areas of patient health education.

Breast Feeding↗
PubMed2004

Lineage allocation and cell polarity during mouse embryogenesis.

The first developmental lineage allocation during the generation of the mouse blastocyst is to outer trophoblast or to inner pluriblast (inner cell mass; ICM) cells. This allocation seems to be initiated at the 8-cell stage, when blastomeres polarise. Polarisation is followed by differentiative divisions at the subsequent two cleavage divisions to generate polar outer and non-polar inner 16- and 32-cells. The key events in polarisation are regulated post-translationally through a cell contact-mediated pathway, which imposes a heritable determinant-like organisation on the blastomere cortex. Two proteins in particular, E-cadherin and ezrin, are intimately involved in the generation and stabilisation of developmentally significant information. Transcriptional differences between lineages appear to follow and may coincide with the lineage commitment of cells.

Animals↗
PubMed2004

The direct measurement of embryogenic volume and nucleo-cytoplasmic ratio during mouse pre-implantation development.

After fertilization, the mammalian conceptus undergoes cleavage, a process of cell proliferation in the absence of interphase growth. It is not known when cleavage ends and gives way to fully replicative cell cycles with a stable nucleo-cytoplasmic ratio. We have used two-photon excitation and confocal microscopy to measure directly volumes and nucleo-cytoplasmic ratios of whole murine concepti and their individual constituent blastomeres during pre-implantation development up to the early uterine attachment stage (day 5). We show that the total cytoplasmic volume of the conceptus remains constant during pre-implantation development, and that the average nucleo-cytoplasmic ratio increases exponentially throughout the same period. Data from individual blastomeres show that both volume and nucleo-cytoplasmic ratio diverge in the inner and outer subpopulations evident from the 16-cell stage (fifth developmental cycle) onwards. Cells from emergent outer trophoblast populations are larger and have smaller nucleo-cytoplasmic ratios than those from emergent inner pluriblast populations. Moreover, the nucleo-cytoplasmic ratio of the trophoblast appears to be stabilizing, suggesting that for this subpopulation cleavage may end at the 16-32-cell transition. Putative hypoblast and epiblast cell subpopulations within the pluriblast were not distinguishable by volume or nucleo-cytoplasmic ratio. Embryonic stem cell volume was higher than that of either cell subpopulation of expanded blastocysts, and their nucleo-cytoplasmic ratio was similar to that of trophoblast cells.

Animals↗
PubMed2002

An innovative approach to developing the reflective skills of medical students.

BACKGROUND: Development of the reflective skills of medical students is an acknowledged objective of medical education. DESCRIPTION: Description of an educational exercise which uses an email-based process for developing the reflective skills of undergraduate medical students. Student quotations illustrate learning outcomes qualitatively. DISCUSSION: The process described is immediate, direct, linked to learning objectives, enables rapid responses to be given to the students individually, and is followed by group sharing of learning. It provides a rigorous and robust feedback loop for students. It is relatively economic for teachers and incidentally benefits curriculum design and evolution. The approach supports development of a reflective approach to learning.

Education, Medical, Undergraduate↗
PubMed2002

The art of regulation and the regulation of ART: the impact of regulation on research and clinical practice.

How a society regulates Assisted Reproduction Technologies (ART) depends on cultural context. The challenge for the regulatory regime is to balance protection for patients and society with freedom for medico-scientific creativity. Neither an exclusively market-regulated nor a peer-regulated approach is realistic politically, or desirable socially, ethically and legally. Legitimate social issues that go beyond the exclusive expertise of doctors and scientists or market choice by patients need to be accommodated within the regulatory regime. Within this context, four key issues are discussed: the lack of a shared social ethic that helps the needs of the community to be balanced against those of its individual members; the negative impact of intrusive external regulation on scientists and doctors; the requirement for doctors and scientists to review their professional structures reflectively and critically if they are to be entrusted with peer-regulation; and the desirability of constructive dialogue between regulators and regulated rather than the use of coercion and criminal sanctions.

Australia↗
PubMedDate not supplied

Circadian clockwork genes are expressed in the reproductive tract and conceptus of the early pregnant mouse.

Circadian genes are expressed in some peripheral tissues, but the expression status of the female reproductive tract and the conceptus over the preimplantation period is unknown. Oocytes, uterine, oviducal tissues and preimplantation conceptuses from days 1-4 of mouse pregnancy were analysed for transcript presence by reverse transcription polymerase chain reaction. Transcripts encoded by the seven known mammalian canonical circadian genes (Per1-3, Cry1-2, Bmal1 and Clock), plus the mammalian genetic homologue of the Drosophila canonical gene Timeless, were detected in the uteri and oviducts taken from mice on days 1-4 of pregnancy and in unfertilized oocytes. After fertilization, transcripts for Per1, Cry1, Bmal1, Clock and Tim have been detected unambiguously. Transcript levels for each of these five genes fall at the two-cell stage, but are restored rapidly for Per1, Cry1 and Bmal1, presumptively by zygotic gene expression. In contrast, transcripts for Clock and Tim recover more slowly. It is concluded that circadian genes are expressed, and may therefore have a role, during the early development of the mammal.

Animals↗