The effect of leupeptin, a serine protease inhibitor, on the fertilization and development potential of oocytes stimulated to undergo cortical granule exocytosis has been investigated. An in-vitro bioassay system was used in which mouse oocytes were exposed to calcium ionophore, A23187, in the presence and absence of leupeptin, before their fertilization and development to the blastocyst stage was assessed. We have demonstrated that the presence of leupeptin in the incubation medium, at concentrations of 1 micrograms/ml and 10 micrograms/ml during the first 10 min of cortical granule exocytosis, reversed the ionophore-induced decrease in the capacity of oocytes to fertilize and develop to blastocysts. The induction of exocytosis of cortical granules by calcium ionophore was confirmed using fluorescence microscopy. Using this technique, we also confirmed that leupeptin did not inhibit ionophore-induced cortical granule exocytosis, thus supporting the contention that leupeptin acted upon released cortical exudate. It was concluded that leupeptin acted by inhibiting proteases released into the perivitelline space during the early stages of cortical granule exocytosis. Based on these results it was proposed that leupeptin could be used to prevent premature loss of fertility of human oocytes which are inadvertently activated under in-vitro conditions.

In this paper we attempt to sharpen and to provide an answer to the question of when human beings first become conscious. Since it is relatively uncontentious that a capacity for raw sensation precedes and underpins all more sophisticated mental capacities, our question is tantamount to asking when human beings first have experiences with sensational content. Two interconnected features of our argument are crucial. First, we argue that experiences with sensational content are supervenient on facts about electrical activity in the cerebral cortex which can be ascertained through EEG readings. Second, we isolate from other notions of a 'functioning brain' that which is required to underpin the view that a cortex is functioning in a way which could give rise to rudimentary conscious experiences. We investigate the development in the human fetus of the anatomical and chemical pathways which underpin (immature) cortical activity and the growth and maturation of the electrical circuitry specifically associated with sensational content in adult experience. We conclude (tentatively) that a fetus becomes conscious at about 30 to 35 weeks after conception; an answer based on a careful analysis of EEG readings at various stages of cortical development. Finally, we survey the possible ethical ramifications of our answer.

Summary. Using in vivo microscopy we investigated endometrial microvascular events occurring on days 5 and 6 of pregnancy at the time of implantation. Blood flow through the endometrium was visualized using incident-light fluorescence microscopy and a video image was recorded for subsequent analysis. At 17:00 h on day 5 of pregnancy it was not possible to identify the impending implantation site from the in vivo appearance of the subepithelial capillary plexus. At 09:00 h on day 6 of pregnancy the embryo implantation site was recognized as an avascular area surrounded by large diameter vessels. These were highly susceptible to haemorrhage when handled. Capillaries closest to the embryo had the greatest diameters, averaging 18\m=.\5\ m=+-\2\m=.\5\g=m\m, and capillary diameters decreased to 7\m=.\5\m=+-\ 0\m=.\4 \g=m\mby 2000 \g=m\m from the embryo. It was also observed that blood flow through larger diameter vessels was sluggish with frequent reversals and stoppages. Leucocyte rolling and adhesion were also common features in these larger vessels. These data indicate that changes in capillary diameter occur in response to local signals associated with the implanting rat embryo. The embryonic or local endometrial signals that mediate these major microvascular changes remain to be elucidated.

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