The development of the suprarenal gland in the albino rat with a consideration of its possible relation to the origin of foetal movements.код для вставкиСкачать
THEDEVELOPMENTOFTHESUPRARENALQLANL) I N T H E ALBINO RAT, WITH A CONSIDERATION O F I T S POSSIBLE RELATION TO T H E ORIGIN O F FOETAL MOVEMENTS DAVID S. PANKRATZ College of Medicine, T h e University of Tennessee, and The W i s t a r Institute of A n a t o m y and Biology ELEVEN FIGURES In this preliminary publication a study of the development of the suprarenal gland is presented, from the time that the gland first appears in embryos of higher vertebrates to the end of foetal life. Special attention has been given to the migration of sympatho-chromaffin cells and the development of associated nerve fibers, since it was early noted by the author that these processes immediately precede the appearanfie of foetal movements and may, therefore, be causally related to the latter. In the present article attention will be focused on the coincidence in development of the suprarenal gland and foetal movements. MATERIAL Through the courtesy of the staff of The Wistar Institute in Philadelphia, an extensive collection of serially sectioned rat embryos was made available to the author. The material also included some rats that Angulo ('28) had studied and other series especially prepared by the institute f o r this investigation. The writer wishes here to express his appreciation and. gratitude to the staff of The Wistar Institute of Anatomy and Biology and especially to Dr. G . E. Coghill, who first suggested the problem and whose candid, kind, and mature criticism has made this woik possible. 31 T H E ANATOMICAL RECORD, VOL. 49, NO. 1 32 DAVID S. PANKHATZ OBSERVATIONS The suprarenal glands in the albino rat appear first in the thirteen-day-old foetus. I n the twelve-day-old foetus no thickening of the epithelium in the dorsal wall of the coelomic cavity can be seen (fig. 1). A slight thickening of the coelomic epithelium medial to the cephalic portion of the mesonephric fold marks the anlage of the suprarenal cortex. This process is due to a proliferation of coelomic epithelium in a fold which is continuous with the pleuroperitoiieal fold cephalically and with the genital fold caudally. This is described in man by both Zuckerkandl ('12) and Wieman ('20). The ABEREVIATTONS F O R A L L FIGURES Ao., aorta Ad.An., adrenal arilage Ad.C., adrenal cortex B.C., blood cells C.C., cortical eells C.V., central vcin G.C., ganglion cells L., liver H.,mesentery Ns.,mesonephros M.T.,inesonepliric tubulcs N . F . , nerve fibers N.Npl., splanchnic nerve P., pleuroperitoneal cushion P.C., pleuroperitoneal cavity P.Ep., peritoneal epithcliuin S., stomach Sp., spleen Sup., suprarenal s ~ p . L . ,suprarerial ligainent Sy.C., sympatho-chromaffin eells (medulla) Sy.C.R., sympatho-chromaffin ' ros4tte ' Sy.G., sympathetic ganglion V., vertebra rjl. Fig. 1 Transverse section tlirongh a twelve-day-old rat foetus. X 330. 33 SUPRARENAL-GLAND DEVELOPMENT I N T H E RAT epithelial cells in this region become definitely larger, their nuclei vesicular, and they appear to migrate into the mesenchyme dorsally (fig. 2). This process in the rat is much like that described in the bird by Hays ( '14), in the pig by Whitehead ('03) and Weyman ('22), and in man by Zuckerkandl ( '12) and Fischel ( '29). Such a complex development of the cortex as described in man by Keene and Hewer ('27) was not observed in the rat. Fig. 2 Transrerse section through a thirteen-day-old rat foetus. X 330. I n the fourteen-day and fifteen-day foetuses the thickening of the epithelium and its dorsal migration were more apparent (figs. 3 and 4). I n these stages one could also see the sympathetic trunk and its ganglia, the aorta, mesonephric tubules, and stomach in their relation to the suprarenal anlage. Growth at this time is rapid, as the figures indicate. During the fifteenth t o the sixteenth days the cortex forms a T H E I N A T O J I I C A L RECORD, VOL. 49, N O . 1 34 DAVID S. PAKKRATZ marked oval mass which protrudes into the dorsal coelomic cavity (figs. 4 and 6). This corresponds to the 25-mm. stage of man described by Keene and Hewer ('27). At this stage of development of the cortex, there is a 'breaking up' of the cortex by small blood vessels, which, according to Wieman ('ZO), probably later form the central veins (fig. 4). I n the sixteen-day f oetnses, shortly before motility was observed (Swenson, '27), the cortex is very spongy, due to Sy. G. Ao. I I Fig. 3 Transverse section through a fourteen-day-old r a t foetus. X 200. the numerous vascular spaces which later are invaded by sympatho-chromaffin cells (fig. 6). About the sixteenth day, small darkly staining cells migrate ventrally from the sympathetic ganglia toward the cortex. Soulie ('03) describes the beginning of penetration of the cortex by the sympathochromaffin cells in a 15-mm. rat embryo and their reunion into a central nucleus in a 25-mm. embryo. Just before movements were first observed, masses of small darkly staining cells can be seen on the medial surface of the SUPRABENAL-GLAND DEVELOPMENT IN THE RAT 35 cortex. Sometimes one may find even a definite mass of these cells in this position (fig. 8). At the time of first motility small clumps of the migrating cells are found lying in the vascular spaces of the medial part of the cortex. I n the defi- Fig. 4 X 330. A nearly longitudinal section through a fifteen-day-old rat foetus. nitely motile foetuses (sixteen days) I often observed a marked bundle of nerve fibers and ganglionic cells along their course (figs. 6 and 6a). Fischel ('29) says that the suprarenal gland in man remains connected with the sympathetic chain by the processes of 36 DAVID S. PANKRATZ these migrating cells which eventually form the medulla. The processes on some of the large ganglion c,ells (G.C., fig. 6a), observed in only a few cases, appear to corroborate his observations. Apparently there are two types of sympatho-chromaffin cells that migrate into the cortex besides the comparatively f etv large ganglioilic cells. The small darkly Fig.5 A section through the suprarenal cortex of a non-motile sixteen-day- old r a t foetus, showing a mass of sympatho-chromaffin cells in a vascular space. x 2000. staining cells are the most numerous, especially in the early stages of cell migration. Then there are larger and paler cells with somewhat vesicular nuclei and cytoplasmic processes (fig. 6a). For a more detailed description, the reader is referred to the article by Keene and Hewer ('27). In all the rat series examined (about twenty-five series) only a few large ganglionic cells were found in the medulla SUPRARENAL-GLAND DEVELOPMENT I N THE BAT 37 of various ages up to birth (fig. 10). On the other hand, I have often observed 'rosettes' of darkly staining cells in the suprarenal gland of the actively motile rat foetuses. These have been described in man by Keene and Hewer ( '27). Figure 9 shows such a 'rosette' with a bundle of nerve fibers connected t o it. P Fig. 6 Transverse section through a motile sixteen-day-old rat foetus. X 100. This cell migration, which began during the sixteenth day, continues during the following days, apparently till birth (figs. 6, 6a, 7, and 8). I n all the foetuses of seventeen, eighteen, and nineteen days definite nerve connections to the gland could be seen (figs. 6,7, and 8). Mitsukuri ( '82) shows, in figure 7, a 23-mm. rat embryo with nerve fibers passing into the suprarenal mass. Soulie ( '03) gives a short description, but does not show any figures f o r the rat. 38 DAVID S. PANKRATZ I n the rat at birth a very definite nerve (N.SpZ., fig. 11) connects the suprarenal gland with the sympathetic chain. The medullary cells are found around and in the vascular spaces, closely crowded against the cortical cells (fig. 11). Fischel ('29) describes such a relation in the suprarenal in man. G. Fig. 6a A section showing a higher magnification of the migrating cells of scction shown in figurc 6. X 2000. DISCUSSION A survey has been made of the literature dealing with the development of the suprarenal gland, the migration of sympatho-chromaffin cells, the first chromaffin reaction, and the origin of foetal movements. Numerous writers, notably Souli6 ('03) and Lutz and Case ( ' 2 5 ) , state that undoubtedly the adrenal hormone is present and capable of functioning at a very early age in the mammalian foetus. They also call attention to Penger's ('12) observations which suggest that SUPRARENAL-GLAND D E V E L O P M E N T I N T H E RAT 39 the suprarenal glands have a relatively more important r81e in the embryo than in the adult. From the phylogenetic point of view Gaskell ('19) points out the fact that in the lowest vertebrates the function of the sympathetic nervous system is largely taken over by a chromaffin system. Such facts give credence to the view that in the embryos of higher vertebrates Fig. 7 Transverse (motile). X 100. section of a seventeen-day-and-five-hour-old rat foetus the suprarenal medulla may function before the sympathetic nervous system. Probably the most complete description of all phases of investigation is available for the chick. Preyer ('85) was the first investigator to study the embryonic movements of the chick extensively. The first movements were noticed in a five-day-old embryo and consisted in a bending of the back from side t o side. Later, Clark and Clark ( '14), with more refined methods, further studied the development of the 40 DAVID S . PANKRATZ embryonic movements in the chick. Their findings corroborate Preyer's work. They describe the early stages as consisting of passive movements of the head, tail, and extremities. They further observed that during the sixth and seventh day the bending of the body becomes more pronounced, the tail contracts independently, the head nods, and the Fig. 8 Transverse section of an eighteen-day-and-six-hour-oldrat foetus (motile). X 330. paddle-like extremities are moved inward and outward. From the eighth to eleventh day, the movements continue to increase in strength and variety. In the same year, Hays ( '14) described the development of the adrenal glands in birds, using the chick. He states that the first evidence of any connection between the anlagen of the prevertebral sympathetic plexuses and chromaffin substance is seen after 130 hours of incubation (5.4 days). After SUPRARENAL-GLAND DEVELOPMENT IN THE RAT 41 168 hours (seven days) of incubation, the cells which are to form the medulla of the gland are beginning to show some differentiation. During the next twenty-four hours, or the eighth day, the chromaffin cells within the glands have increased greatly in number, and most of the sympathetic cells have disappeared from the surrounding mesenchyme. The arrangement of the chromaffin cells undergoes a marked change during the ninth day of incubation. At the same time I Sy.C.R. Fig. 9 A section showing a sympatho-chromaffin 'rosette' in an eighteen-dayand-six-hour-old rat foetus (motile). X 1500. the chromaffin cells are found in small groups arranged around the venous blood vessels. Furthermore, during the period in which there is the greatest influx of cells from the aiilagen of the prevertebral sympathetic plexuses there is also the greatest activity in the development of the vascular systerns. Later, Lutz and Case ('25) and Okuda ('28) investigated the appearance of adrenalin in the chick by biological and chromic reaction tests. Using the enucleated frog's eye, Lutz and Case ('25) obtained the first positive adrenalin reaction in seven-day-old chick embryos. Okuda ('28) used 42 DAVID S. PANKRATZ Cannon’s intestinal method and the chromic-acid reaction. He says: . . . , in the chick embryo the suprarenal adrenalin appears on about the eighth day of incubation, and chromic reaction of the gland cells sets in a t nearly the same time. Their intimate relation which Ogata (’16) pointed out, is thus confirmed. The adrenalin content of the glands increases gradually with the progress of development in a n incubator, but a more o r less marked increment is found on the 13th to 21st days. Fig. 10 A section showing a ganglion cell in the suprarenal gland of an eighteen day-and-four-hour-old rat foetus (motile). X 1500. I n the chick we see that the positive tests for adrenalin appeared a few days after the migration of the sympathochromaffin cells. On the basis of Miller’s ( ’26) and Weyman’s ( ’22) observations, possibly the actual beginning of the formation of adrenalin in the chick takes place somewhat earlier SUPRARENAL-GLAND DEVELOPMENT I N T H E RAT 43 (fifth to sixth day) than has been described at the present. From other investigations it appears that there is a production of adrenalin even during the later part of the sympathochromaffin cell migration. Concerning the development of the suprarenal medulla and the appearance of adrenalin in the mouse, &filler (’26) gives C. Fig. 11 Transverse section through a rat a t birth. X 70, a full account. According to her observations, the first appearance of the chromaffin reaction takes place between the latter part of fourteenth day and the first half of the fifteenth day. “This,” she states, “is at a time when the future medullary cells are just beginning their penetration between cortical cells, leaving the sympathetic ganglion anlage, o r 44 DAVID S. PANKRATZ sympatho-chromaffin mass, which is closely applied to the suprarenal cortex at this time.’’ Her observations are based on both the chromic reaction and Cannon’s intestinal method. She also observed that the seventeen-day foetuses were highly moti1e.l Inaba (’91) gives probably the earliest account of the development of the suprarenal in the mouse. He gives figures showing the final nerve connections of the gland, Some observations have also been made on the rabbit. According to Kolliker, the suprarenal bodies in the rabbit appear first, on the twelfth or thirteenth day of gestation, as masses of somewhat large round cells on each side of and ventral to the aorta. On the fourteenth day the suprarenals are already well marked (Mitsukuri, ’82). They consist of a mass of cells with large nuclei, divided into indefinite cords by blood capillaries which are already somewhat numerous. Mitsukuri (’82) states that at this stage the connection of the gland with the sympathetic chain, by means of a mass of cells, is not so obvious as later on. But in the suprarenals of the sixteen-day-old embryos great changes were observable. Mitsukuri says that the medullary part (m., fig. 5) surrounded for the most part by the cortical substance ( c ) can now be clearly distinguished. I n the same figure he shows a branch ( a ,fig. 5) of the nervous mass ( n ) passing into the suprarenal and uniting with the medullary substance ( m ) . Minot (’97) describes a similar development of the suprarenal in the rabbit. Kohn (’03) noted the presence of the chromic reaction as early as the period of beginning migration of the future medullary cells into the suprarenal cortex. I n the fourteen-day foetuses he was unable to detect any chromaffin cells. I n fifteen-day rabbit foetuses he first observed the chromaffin cells lying medially to the cortex; and in the sixteen-day foetuses the reaction was very definite and the sympatho-chromaffin cells are penetrating the cortex. This penetration, according to Kohn (’03)’ is much more rapid in the rabbit than in man. Soulie (’03) likewise says that about the end of the fourteenth day one is able to see a mass of Information on motility was given to the author by personal communication. SUPRARENAL-GLAND DEVELOPMENT IN THE RAT 45 sympathetic ganglion cells in contact with the cortex. About the fifteenth day the cortex receives a definite fasciculus of fibers, but is not penetrated by the future chromaffin cells. The first stage of motility-in the form of ventrolateral flexion of the head and upper trunk (as described by Swenson ('27) in the rat and by Windle ('30) in the cat)-has been first observed by the writer in fifteen-day and seventeen- to twenty-hour rabbit foetuses.2 The observations on the cat seem to suggest a similar relation. Zuckerkandl ( 'la), speaking of the development of the suprarenal in man and in the cat, says, "thus, for example, in an 11mm. cat embryo the suprarenal ridge does not project as much as in man." He further compares an 11-mm. human embryo as being similar to a 10-mm. cat embryo in suprarenal development. Kohn ( '03) first differentiated the sympathochromaffin cells in the ganglionated chain in a 12-mm. S.S.L. cat embryo. Soulie ('03), in his description of the development of the suprarenal of the cat, says: . . . . cet mas, d ' bbord homoghe, parait composit de nodules secondaires sup les embryons de 1 4 mill., et prend u n aspect nettement reticule sur les embryons de 16 mill. C'est entre les stades 16 et de 18 mill. que commence la pitnittration des Blitments parasympathiques, cette penetration est a peu pres achevite sur les embryons de 4 cent. Recently, Windle ('30) has observed the first foetal movements in cat foetuses 17.5 and 18.5 mm. in length. I n man the status of our information is in an unsettled condition. Souli6 ( '03), Keene and Hewer ( '27), and Fischel ('29) state that the cortex in man appears in a 5-to-6-mm. embryo. Other investigators give slightly different ages. Sonlii.5 ('03) says that the cortex develops rapidly, and in a 19-mm. embryo. According to Fischel ( 'as), the migration of sympatho-chromaffin cells into the cortex takes place in 14to 20-mm. embryos. Keene and Hewer ('27) describe and figure the beginning of such a migration in a 12-mm. embryo, and show that it becomes prominent in twelve- to twenty-twoweek embryos and ceases at full term. I n the 25-mm. stage, a The data on these observations have not been published. 46 DAVID S. P A N B R A T Z according to their observations, the suprarenal gland is defined and consists of true cortex, foetal cortex, and immigrating sympatho-chromaffin bundles. Jordan and Kindred ( '30) also state that the migration begins at about the 19-mm. stage and continues until after birth. Gradually the primordial chromaffin cells surround the central vein, which appears at about the 23-mm. stage, and ultimately differentiate into characteristic chromaffin cells. Various early investigators have failed to find any adrenalin in the suprarenal gland of human foetuses. On the other hand, recent works show that the adrenalin begins in relatively young foetuses. Hammar ('25) says that the chromaffin cells appeared first in an embryo of 22.2-mm. length, and that at that time the paraganglionic cords began to be distinguishable. According to Keene and Hewer ( '27), adrenalin appears at twelve weeks, and the chromaffin reaction appears at twenty-two weeks. Fenger ( '12) furthermore says that in every case one finds adrenalin stronger relatively in the embryo than in the adult. The first motility in the human foetuses has been observed as follows: Motility in the arm at 2 em. C.R. (Yanase, '07) ; spontaneous motility in the arms and legs at 2.2 em. C.R. (Strassmann, '00-'03) ; and oral reflex, with associated leg movement, at 3.5 em. C.R. (Minkowski, '28). After this age, other investigators (Bolaffio and Artom, '23-'24 ; Erbkam. '37 ; and Krabbe, '12) have noted various types of early foetal movements. For a more detailed discussion of these movements the reader is referred to Coghill's paper ('29). Due to lack of material and uniform standard of age and lengths, when dealing with human material, definite conclusions cannot be readily formulated. The latest investigations in the vertebrates studied point to a definite relation between the migration of sympathochromaffin cells, the chromic reaction, and the appearance of adrenalin. Likewise, foetal movements, in the forms studied, apparently begin at approximately the same stage of development. This striking parallelism has suggested a possible SUPRARENAL-GLAND D E V E L O P M E N T I N THE RAT 47 relationship of cause and effect which is now being investigated in a number of different mammals. Tabulated summary of the data and discussion T H E MIGRATION OF IYMPATHO-CHROMAFFIN CELLS Chick Mouse Rat Rabbit Cat Man T H E CHROMIC 1 T H E ADRENALIN REACTION 8th day 130 hours; 5.4 days 14th-15th day 15th-16th day 15th-16th day 16-18 mm. 14-20 mm. ? ? j ? I 22 weeks ? B 1 2 weeks EARLY MOTILITY 5th day Very motile a t 17 days 16th day 15th-16th day 17.5 and 18.5 mm. 2-3.5 em. CON.CLUSION The suprarenal gland in the albino rat appears first in the thirteen-day-old foetus. A slight thickening of the coelomic epithelium medial to the cephalic portion of the mesonephros marks the anlage of the suprarenal cortex. During the fifteenth to the sixteenth day the cortex forms an oval mass which protrudes somewhat into the dorsal coelomic cavity. About the sixteenth day, just before foetal movements begin, cells migrate from sympathetic ganglia toward the cortex. At the time (sixteen days or more) when foetal movements have first been observed, a definite mass of sympathochromaffin cells is located among the medial cell cords of each cortex. This cell migration continues during the seventeenth and eighteenth days and possibly till birth. I n seventeen-, eighteen-, and nineteen-day foetuses nerve fibers which connect the gland with the sympathetic chain were observed with large ganglionic cells along their course. From the literature on the different phases of the development of the suprarenal gland and appearance of foetal movements in the chick, mouse, rabbit, cat, and man, the author concludes that there is in these animals a coincidence in development of gland and foetal movements similar t o that which obtains in rat embryos. These facts have suggested that the beginning of foetal movements may, perhaps, be facilitated by hormones of the embryonic gland in some such way as adrenalin is 48 DAVID S. PANKRATZ known to affect the threshold of skeletal muscle in adultsa hypothesis that is now being subjected to experimental methods. BIBLIOGRAPHY A. W. 1929 h’eurological interpretation of fetal beANGULOY GONZ~LEZ, havior: The motor-cell columns of the albino rat before birth. Anat. Rec., vol. 42, p. 17. 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