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Biomedical subjects

B C Heng

Publications and source records attributed to B C Heng.

9 recordsLinked to original sources

Ethical issues in transnational "mail order" oocyte donation.

The rising demand for donor oocytes in developed countries has led to what is referred to as transnational or international oocyte donation, or the outsourcing of oocyte donation to poorer countries. In a further twist, frozen sperm from a recipient's partner can also be mailed to a foreign clinic to fertilize donor oocytes, and the resulting embryos are mailed back, cryopreserved, for transfer to the recipient. Among the numerous ethical concerns raised by this practice of mail order oocyte donation, the most obvious are that underprivileged women from poorer countries are often exploited; fertility physicians from richer counties abdicate responsibility for the welfare of donors; and responsibility could become an issue of contention if transmission of disease to the oocyte recipient or congenital defects in offspring born from such oocyte donation were to occur. Moreover, savings from utilizing donors from poorer countries ought to be shared with oocyte recipients.

Bioethics↗

The advent of international 'mail-order' egg donation.

The rising demand and increasing scarcity of donor oocytes in developed countries have led to some fertility clinics sourcing oocyte donors from abroad, particularly from poorer countries, in what is referred to as 'transnational' or 'international' oocyte donation. In a further new 'twist' to this scheme, frozen sperm of the recipient's male partner is exported abroad through courier mail and is used to fertilise donor oocytes in a foreign clinic to produce embryos, which are then cryopreserved and imported back by mail for transfer to the woman. There are numerous ethical concerns with regards to such means of procuring donor oocytes. First, there is an issue of exploiting economically underprivileged women in poorer countries and disproportionate gains on the part of medical doctors and fertility clinics. Second, there is a question of abdication of responsibility for the donor's welfare on the part of the fertility doctor who takes charge of the recipient's treatment abroad if oocyte donors were to develop severe ovarian hyperstimulation syndrome. Third, the issue of responsibility and accountability becomes even more contentious if congenital defects were to appear in offsprings born from transnational oocyte donation or in the case of transmission of communicable diseases such as hepatitis B, syphilis and AIDS to the recipient. Last, cost savings from the lower prescription price of fertility drugs in economically less-developed countries may not be passed down to the oocyte recipient but instead be exploited to boost the already substantial profit margin of fertility clinics and doctors.

Commerce↗

Utilising human embryonic stem cells as "catalysts" for biological repair and regeneration. Challenges and some possible strategies.

In recent years, much interest has been generated over the potential of human embryonic stem cells in transplantation medicine. The ground-breaking study of Fraidenraich and colleagues conclusively demonstrated that rescue of lethal cardiac defects in Id knockout mutant mouse embryos was not due to transplanted embryonic stem cells giving rise to functional new tissues within the defective embryonic heart. Instead, there is indirect evidence that the observed therapeutic effect was due to various secreted factors emanating from the transplanted cells. This therefore introduces the exciting prospect of utilizing human embryonic stem cells as "catalysts" to promote biological repair and regeneration in transplantation therapy. Nevertheless, the immunological barrier against allogenic transplantation, as well as the teratogenic potential of human embryonic stem cells poses major technical challenges. A possible strategy to overcome the immunological barrier may be to impose a temporary regimen of immunosuppressive drugs followed by their gradual withdrawal, once adequate tissue regeneration has been achieved. Other more novel alternatives include the use of microencapsulation to block interaction with the transplant recipient's immune system, and co-transplantation with bone marrow-derived mesenchymal stem cells, which have been demonstrated to possess immuno-suppressive properties. The teratogenic potential of human embryonic stem cells could possibly be alleviated by directing the differentiation of these cells to specific lineages prior to transplantation, or through mitotic inactivation. Co-transplantation with autologous adult stem cells may represent a novel strategy to further enhance the "catalytic" effects of human embryonic stem cells. The various factors secreted by human embryonic stem cells could then have a concentrated localized effect on relatively large numbers of co-transplanted autologous adult stem cells, which may in turn lead to enhanced repair and regeneration of the damaged tissue or organ. This new therapeutic strategy needs to rigorously investigated, in view of its potentially important clinical applications.

Cell Transplantation↗

Slow-cooling protocols for microcapsule cryopreservation.

The relatively large size (300-400 microm) and fragile semi-permeable membrane of microcapsules makes them particularly prone to cryodamage. This study investigated slow-cooling protocols for the cryopreservation of microcapsules. Instead of a programmable freezing-machine, slow cooling was carried out directly within a -80 degrees C refrigerator. A range of increasing cryoprotectant (DMSO and EG) concentrations with slow cooling was investigated. The results showed that 2.8 M (20% v/v) DMSO and 2.7 M (15% v/v) EG were optimal for microcapsule cryopreservation, resulting in approximately 55-60% of the microcapsules remaining intact, with a relatively high post-thaw cell viability of 80-85%. Post-thaw cell viability and microcapsule integrity were consistently higher at equivalent molarities of DMSO compared to EG. Hence, all subsequent studies utilized only DMSO. Post-thaw cell viability upon slow cooling with 2.8 M (20% v/v) DMSO was significantly improved in the presence of 0.25 M sucrose (> 95%), but there was no enhancement in microcapsule integrity. Neither post-thaw cell viability nor microcapsule integrity was improved with multi-step exposure and removal of sucrose, compared to a single-step protocol. There was also no improvement in either post-thaw cell viability or microcapsule integrity in the presence of 20% (w/v) Ficoll. Hence, the optimal condition for microcapsule cryopreservation by slow-cooling is with 2.8 M (20% v/v) DMSO and 0.25 M sucrose.

Animals↗

Effects of elevated temperature in vivo on the maturational and developmental competence of porcine germinal vesicle stage oocytes.

Postslaughter processing of sow carcasses results in the ovaries being exposed to temperatures of 41.3 to 42.1 degrees C within a 30-min time frame. This study investigated whether the maturational and developmental competence of the recovered germinal vesicle stage oocytes could be compromised by post-slaughter processing. The results showed that the in vitro maturation rates of GV stage oocytes exposed to elevated temperature did not significantly differ from the corresponding controls (74.1 vs. 75.8%). Immunocytochemical staining revealed that elevated temperature did not adversely affect metaphase II spindle formation but resulted in extensive disruption of oocyte cytoskeletal organization. This, in turn, had a detrimental effect on parthenogenetic development compared with the corresponding nonheat-treated controls (cleavage rate = 27.7 vs. 65.3%, P < 0.01; blastulation rate = 6.7 vs. 20.6%, P < 0.01). Hence, transient exposure to elevated temperature during slaughter did not have any detrimental effects on nuclear maturation per se, but it did result in extensive cytoskeletal damage, which in turn drastically decreased the developmental competence.

Animals↗

The analysis of intermolecular interactions in concentrated hyaluronan solutions suggest no evidence for chain-chain association.

Confocal fluorescence recovery after photobleaching (confocal-FRAP) was used to examine the influence of electrolytes (NaCl, KCl, MgCl(2), MnCl(2) and CaCl(2)) on the network and hydrodynamic properties of fluoresceinamine-labelled hyaluronan (FA-HA) at concentrations up to 10 mg/ml. Self and tracer lateral diffusion coefficients showed that in Ca(2+) and Mn(2+), FA-HA (830 kDa) was more compact than in Mg(2+), Na(+) or K(+). These results were correlated with changes in the hydrodynamic radius of HA, determined by multi-angle laser-light-scattering analysis in dilute solution, which was smaller in CaCl(2) (36 nm) than in NaCl (43 nm). The permeability of more concentrated solutions of HA (<10 mg/ml) to FITC-dextran tracers (2000 kDa) was higher in CaCl(2). The properties of HA in urea (up to 6 M) were investigated to test for hydrophobic interactions and also in ethanol/water (up to 62%, v/v). In both, there was reduced hydrodynamic size and increased permeability to FITC-dextran, suggesting increased chain flexibility, but it did not show the changes predicted if chain-chain association was disrupted by urea, or enhanced by ethanol. Oligosaccharides of HA (HA(20-26)) also had no effect on the self diffusion of high-molecular-mass FA-HA (830 kDa) solutions, or on dextran tracer diffusion, showing that there were no chain-chain interactions open to competition by short-chain segments. The results suggest that the effects of electrolytes and solvent are determined primarily by their effect on HA chain flexibility, with no evidence for association between chain segments contributing significantly to the major properties.

Fluorescent Dyes↗

The molecular basis of the solution properties of hyaluronan investigated by confocal fluorescence recovery after photobleaching.

Hyaluronan (HA) is a highly hydrated polyanion, which is a network-forming and space-filling component in the extracellular matrix of animal tissues. Confocal fluorescence recovery after photobleaching (confocal-FRAP) was used to investigate intramolecular hydrogen bonding and electrostatic interactions in hyaluronan solutions. Self and tracer lateral diffusion coefficients within hyaluronan solutions were measured over a wide range of concentrations (c), with varying electrolyte and at neutral and alkaline pH. The free diffusion coefficient of fluoresceinamine-labeled HA of 500 kDa in PBS was 7.9 x 10(-8) cm(2) s(-1) and of 830 kDa HA was 5.6 x 10(-8) cm(2) s(-1). Reductions in self- and tracer-diffusion with c followed a stretched exponential model. Electrolyte-induced polyanion coil contraction and destiffening resulted in a 2.8-fold increase in self-diffusion between 0 and 100 mM NaCl. Disruption of hydrogen bonds by strong alkali (0.5 M NaOH) resulted in further larger increases in self- and tracer-diffusion coefficients, consistent with a more dynamic and permeable network. Concentrated hyaluronan solution properties were attributed to hydrodynamic and entanglement interactions between domains. There was no evidence of chain-chain associations. At physiological electrolyte concentration and pH, the greatest contribution to the intrinsic stiffness of hyaluronan appeared to be due to hydrogen bonds between adjacent saccharides.

Animals↗