Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.

Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions.

Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during foetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and foetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytotrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca(2+)]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers invitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.

Twin reversed arterial perfusion (TRAP) sequence in association with VACTERL association: a case report.

INTRODUCTION: Twin reversed arterial perfusion (TRAP) sequence is a rare complication of multiple pregnancy caused by defects in early embryogenesis. The pump twin supplies the acardiac recipient twin with blood, and although the pump twin is usually structurally normal, congenital anomalies have sometimes been reported. We report a unique case of twin reversed arterial perfusion sequence with a prenatal diagnosis of VACTERL association in the surviving pump twin. CASE PRESENTATION: A 24-year-old Caucasian woman presented at 11 weeks' gestation with a monochorionic, monoamniotic twin pregnancy. A reversed arterial flow was noted on a Doppler imaging study coming from the larger, apparently normal twin to the smaller, grossly abnormal twin, and a diagnosis of twin reversed arterial perfusion sequence was made. Cardiac activity was undetectable in the recipient twin by 16 weeks' gestation. Further detailed assessment at 18 weeks' gestation revealed multiple congenital anomalies of the surviving pump twin, in keeping with a diagnosis of VACTERL association. A live infant girl was delivered at 39 weeks by elective cesarean section. She underwent extensive surgery with subsequent normal development at the age of two years. CONCLUSION: The co-existence of two rare and complex conditions in this unique case raises interesting questions about the role of early defects in embryogenesis and their subsequent effects on fetal development. This case also highlights the importance of prenatal diagnosis of major congenital anomalies to the plan treatment, reduce morbidity and aid the survival of affected children.

Triorchidism at orchidopexy: a case report.

INTRODUCTION: Polyorchidism is defined as the presence of more than two testes. The management of this rare condition is still debatable, particularly when it is an incidental finding at surgery. CASE PRESENTATION: We present the case of an 8-year-old boy with triorchidism found incidentally during an elective orchidopexy. This supernumerary, ectopic and atrophic testis was removed to avoid an increased risk of malignancy. CONCLUSION: Risk of malignancy justifies the removal of an atrophic and ectopic testis in triorchidism. However, it would appear safe to preserve a viable intrascrotal supernumerary testis found incidentally at surgery provided that the patient is followed up in the long term.