Increase in zymogen granule volume accounts for increase in volume density during prenatal development of pancreas

The sudden increase in volume density of zymogen granules in acinar cells of the fetal rat pancreas was examined with particular attention to the respective roles of granule size and number in this event. Volume density increased some twelvefold, from about 3% of cytoplasmic volume at 17 days to about 45% at 20 days, following a sigmoidal pattern in which the greatest rate of increase occurred during day 18. This increase in volume density was primarily the result of an increase in granule volume. Zymogen granule diameter increased from 0.55 micron at 17 days to 1.20 micron at 20 days, an order of magnitude increase in average granule volume. The total number of granules in the tissue increased in proportion to the increase in organ weight (cell number and size), but changes in the number of granules per unit cytoplasmic volume were minor (+ 40%) in comparison to the increase in volume density. The distribution of granule diameter was roughly normal and unimodal at each time interval, and the increase in average diameter over time was marked by an increase in the upper limit of the size distribution and an increased percentage of large granules. The size of condensing vacuoles also increased during this period, and their distributions were roughly coextensive with those seen for zymogen granules at the same time. The potential origins of changes in granule size are discussed, as well as the important effect that size has on the number of granules observed in "two-dimensional" tissue sections viewed in the electron microscope. If size is not considered in our estimates, then we underestimate the numerical density in cells with small granules compared to those with large granules. The results indicate the central role of granule size, as opposed to number, in determining granule volume density in the embryonic pancreas.