A c t 8 P a t h . Jap. 27(1): 41- 50, 1977
EXPERIMENTAL RAT CHORIOCARCINOMA
-An Electron Microscopic Study Kennichi KAKUDO Department of Pathology, Osaka University Mea'ical School (Received on April 15, 1976) Experimental choriocarcinomas of the rat were studied with electron microscopy and compared with the ultrastructure of rat trophoblasts at mid-and late-gestational stage. The choriocarcinoma numbered m-803 contained abundant cytoplasmic organellae and was quite similar to the trophospongial cell a t late- gestational stage. The m-801 closely resembled the trophospongial cell a t mid-gestational stage. The m-673, which has 3beta-ol dehydrogenase enzyme system," could not be studied sufficiently inspite of the examination of more than 30 blocks of epon embedded specimen, because of the degeneration and necrosis occurring in the specimens. ACTA PATH. JAP. 27: 41-50. 1977.
There is only a limited number of literatures on experimental choriocarcinoma of the rat.leJ8J4 The local application of chemical carcinogen in the placenta of pregnant To our rat had been reported to induce choriocarcinoma in a high incidence!J9 knowledge, there are no reports about spontaneously occurring choriocarcinomas in the rat, and there are no reported studies on the ultrastructure of choriocarcinoma of the rat. The present report deals with the studies on the ultrastructure of rat choriocarcinoma which were induced by M. MIYAMOTO and numbered as m-673, m-801, m803, comparing with rat trophoblasts of increasing gestational stage. Mater&Qls and
Methods
The three primary tumors of rat choriocarcinoma induced in Wistar pregnant rata were The experimental methods of induction of these tumors had obtained from Dr. M. MIYAMOTO. been described elsewhere (M. MIYAMOTO,1971)1* The animals were anesthetized with ether, the tumor specimens were surgically removed and fixed with 3% glutaraldehyde at 4°C (phosphate buffered a t pH 7.3) end postfixed with 1% osmium tetraoxide a t 4°C for electron microscopy. The specimens dehydrated in graded ethanol and embedded in epon. The ultrathin sections were stained with uranyl acetate end lead tartrate. The sections were examined with HU-I1B electron microscopy a t 75KV. The specimens of normal rat placenta of the 12th, IBth, and 20th gestational day were prepared by the same methods.
Obs&k Ultrastructural observations of rat choriocarcinoma were described briefly in a preceeding report! There are common ultrastructural features, such as, few
*2i
s-
Address: Department of Pathology, Osaka University Medical School, Osaka-shi, Kita-ku, Joan-oho 33, Japan. 530 41
42
EXPERIMENTAL RAT OHORIOOARCINOMA
Acta Path. Jap.
Fig. 1. Experimental rat choriocarcinoma m-803. The cell size is larger than the other two. The nuclear outline is 80 pleomorphic with nuclear invaginations that the tumor cell of m803 seems to be a multinucleated giant cell in electron microscope. I n the cytoplasm, there are many polyeomes, short segments of RER end round mitochondria with membranous flat crietae. Original magnification x 5,000, uranyl and lead tartrate.
27(1): 1977
K. KAKUDO
43
Fig. 2. Toluidine blue stained thick section of epon embedded material of rat choriocarcinoma m-803. There are many giant cells with pleomorphic nuclei, but there are no multinucleated giant cells. Original magnification x 400, toluidine blue.
desmosome-like attachments at cell surface and numerous free ribosomes, polysomes and rough-surfaced endoplasmic reticulum (RER) in cytoplasm, but there are much ultrastructural differences between the three rat choriocarcinomas of m-673, m-801 and m-803, as will be noted in the following observations. m803 Three blocks of epon embedded specimens of m-803 were examined for this study. The cell size is larger than the other two with occasional pleomorphic giant cells (Fig. 1) The nuclear outline is so pleomorphic with nuclear invaginations that the tumor cell appears as a multinucleated giant cell on electron microscope. But in toluidine blue thick section (Fig. 2), there is no syncitial type giant cells which are the characteristic feature of human choriocarcinoma. The tumor cells are relatively tightly arranged with few desmosome-like attachments. No microvilli are found on the cell surface. In the cytoplasm, there are many round mitochondrias with membranous flat cristae, polysomes, free ribo.somes and short segments of RER (Figs. 1, 3). Few tonofilamentlike fibers are found in the peripheral cytoplasm. The ultrastructural features of m-803 closely resemble those of trophospongial cell of late gestational stage. m-80 1
Four blocks of epon embedded specimens of m-801 were examined for this study. The tumor cells are relatively tightly arranged and form some desmosome-like
44
E X P m m T A L RAT OBORIOOAMXNOMA
A& Palh. Jap.
Fig. 3. Experimental rat choriocarcinoma m-803. There are few desmoeome-like attachmenta (arrow) between tumor calls. In the cytopleem, there are numeroua polysomea and few tonofilament-like fibers peripherally. Original magnification x 10,OOO, uranyl and lead tartrate.
27(1): 1977
K. KAKUDO
Fig. 4. Experimental rat choriocarcinoma m-801. There are many demosome-like attachments (arrow) between tumor cells. In the cytoplasm, the tumor cell is rich in polysomes and RER. The cell size of m-801 is smaller than that of 111-803. Nuclear invagination is rare. Original magnification x %OW, uranyl and lead tartrate.
attachments between tumor cells (Figs. 4, 5). No microvilli are found on the cell surface. In the cytoplasm, the tumor cells of m-801 are rich in free ribo.sonies, polysomes and RER, and are relatively poor in mitochondria. The tumor cells of m801 are poorly differentiated in development of cytoplasmic organella than ni-803 and closely resemble the trophospongial cell of mid-gestational stage. m-673 Careful study of more than 30 epon embedded blocks of m-673 failed to demonstrate apparent neoplastic epithelial cell nests, because the specimens of 11-673 obtained for the present study were fibrous mingled with degeneration and necrosis. The cells of m-673 demonstrated by electron microscopy are chiefly fibroblastic and surrounded by thick collagen fiber bundles. Few epithelioid cells with denmobsome-likeattachments are occassionally found and the cytoplasm of these cells are rich in polysomes and RER.
l4EpRRJ.lUNTAL RAT OHORIOOAIUJINOMA
Aeto Path. Jap.
Fig. 5. Experimental rat choriocarcinoma m-801. The cytoplasmic organella ie poorly developed except for ribosomee. Deernosome-like attschementa can be seen between tumor cells. Original magnification x lO,OOO, uranyl and lead tartrate.
DisCUSSiora
Spontaneous Occurrence of choriocarcinoma in the rat, and their ultrastructures have not been reported up to date. It is nessesary to compare experimental choriocarcinoma of the rat with normal trophoblasts of the rat ultrastructurally. Review of the ultrastructure of normal trophoblasts of rat placenta with increasing gestational stage is as follows. The rat gestational stage is conveniently divided into four stages in this report. The first is the preimplantational stage1 of 0 to 6th gestational day and the second is the formation of an ectoplacenta3 of 6 to 9th gestational day, which is excluded in this study because it is very difficult to demonstrate the trophoblasts ultrastructurally. The third is the mid-gestational stage of forming a labyrinth of 10th to 18th day and the fourth is the late-gestational stage of maturation and preterm of 19th to 2lst day. Although some of the details of structural organization of rat placenta still contain unsolved problems, the ultrastructure of the trophoblasts of the labyrinth and junctional
27(1): 1977
47
E. KhKUDO
Decidua baaalis
Giant cells
Trophospongial and glycogen cells
Fig. 6. Toluidine blue stained thick section of junctionel zone of normal rat placenta at 16th day. At the top, one can sea decidue beselis which is the maternal element. Note fetal tmphoblesta of trophoblestic gient cells (middle), trophospongial cells and glycogen cells (bottom). Originel magnification x 400, toluidine blue.
zone (basal zone, spongy zone, reticular zone) had been clearly described at mid-and late-gestational stage.*n6n'J6 The labyrinth is called hemotricorial and is composed of four layers, which are three trophoblastic layers and fetal endothelium with basement membrane.2 The junctional zone consists of at least three distinct trophoblastic elements histologically (Fig. 6), which are trophospongial cells (small basophilic cells), glycogen cells and trophoblastic giant cells. It is supposed that the trophospongial cells differentiated into glycogen cells and labyrinthine trophoblasts before the 18th gestattional day, after which all trophoblasts are mitotically inactive.' In addition to it, it is supposed that the trophospongial cells transform into giant cells,4 in other words, the primitive cell of all trophoblasts is the trophospongial cell. The ultrastructural features of these trophoblasts according to its increasing gestational stage had been reported minutdy as follows. The trophospongial cells of the 12th day are small, oval and poorly differentiated (Figs. 7, 8). The nuclear outline often appears to be pleomorphic, and mitosis is occasionally found. In the cytoplasm, the trophospongial
48
IXPMMIKENTAL BAT OHORIOOARCINOMA
A& Paih. Jap.
27(1): 1977
K. gdKUD0
49
cells contain numerous free ribosomes and polysomes, a few RER, ovoid mitochondria and lipoid droplets. In arrangment, the trophospongial cells seem to be epithelioid because they possess some desmosomes. The trophospongial cells of the 16th day are not so different from those of the 12th day as to cytoplasmic organella, but in arrangment they are somewhat looser than that of the 12th day. The trophospongial cells of the 20th day (late gestational stage) are much looser than those of the 12th and 16th day, and are surrounded by amorphous dense material.10 In the cytoplasm, the trophospongial cells of the 20th day are rich in organella, particularlly dilated RER and round mitochondria with membranous flat cristae. The development of RER is so high in degree that the cells vary in size and are somewhat larger than those of the 12th and 16th day. The trophoblastic giant cells of the 12th, 16th and 20th day are not so different in general. The cytoplasmic organellae of giant cells appear more highly differentiated than those of trophospongial cells. There are numerous polysomes, RER, G-olgi apparatus and phagosomes in the cytoplasm, many desmosomes at the cell surface and annulated lamellae in the large nucleus. The glycogen cells can be distinguished by vesicular and clear cytoplasm in light microscope. The cytoplasm contains abundant glycogen particles and a few Gal@ apparatus, RER and mitochondria. The cytoplasmic organellae of the glycogen cells of the 12th, 16th and 20th day are not 80 different in general. The present report suggests that the experimental choriocarcinoma numbered m803 ultrastructurally resembles the trophospongial cell of late getational stage and m801 also resembles the trophospongial cell of mid-gestational stage. It is supposed that m-803 is a well differentiated choriocarcinoma and m-801 a poorly differentiated choriocarcinoma derived from trophospongial cell which is assumed to be a primitive cell of all trophoblasts of the rat placenta. Though the ultrastructural features of m-673 were not fully examined electron microscopically, the epithelioid cells of m-673 is classified as a choriocarcinoma resembling the trophospongial cell of mid-gestational stage, for the time being. In comparison with human choriocarcinoma, rat choriocarcinoma differs greatly from that of human ultrastructurally. In human choriocarcinoma, there are syncytial trophoblastic type cell and cytotrophoblastic type cell". The former is a multinucleated giant cell, which possesses short microvilli and desmosomes at cell surface, and numerous phagosomes, dilated RER and polysomes in the cytoplasm. The latter is small and possesses desmosomes, many polysomes and short segments of RER. In experimental rat choriocarcinoma, there is only one type of cell which resembles a trophospongial cell at various gestational stages, and there is no resemblance to Fig. 7. The trophospongial cell of normal rat placenta at 12th day. Mitoaie is seen in lower left. The cytoplasmic organella is poorly developed except for ribosomes. Original magnification x 5,000, uranyl and lead tartrate. Fig. 8. The trophospongial cell of normal rat placenta at 20th day. There are amorphous dense material (A) at intercellar space end many deamosomea(arrow) between trophospongial cells. Dilated RER and round mitochondria with membraneom flat cristm are well developed in the cytoplaan. Original magnification x 6,000, uranyl and lead tartrate.
glycogen cell and trophoblastic giant cell. It is supposed that the difference might be due to the structural difference of human placenta and rat. A c k n u w W e : The author wishes to exprew his gratitude to Prof. T. M ~ Y ~ Wfor I his advice and support in this investigation, and ale0 to Dr. M. Mrynaamo for allowing us to use. his tumor specimens for the p m n t study. ReferencRp
1. ENDBBB, A.C. and , S.: A morphological analysis of the early implantation etagee in the rat. Am. J. Anat. 120: 186-226, 1967. 2. ENDBBB, A.C.: A comparative study of the h e structure of the trophoblset in several hemochorial placenta Am. J. Anat. 116: 2988,1966. J.W.: Morphological and physiological studies of the placenta in the albino 3. EV&BIUDT, rat. J. Exp. Zool. 70: 243-284, 1936. o R , Histological and fine structural obsewations on the placenta 4. DAVIES,J. and G L ~ ~ s ~S.R.:
6.
6.
7. 8.
9. 10.
of the rat. Part I. Organbation of the normal placenta. Part II. Changes after surgical removal of the fetus (fetectomp). Acta. Anat.169: W2-608, 1968. JOLLIID, W.P.: Fine structural changes in the junctional zone of the rat placenta with increasing gestational age. J. Ultraahcture Rseeech 12: 420-438, 1966. Jo-, W.P.: Fine structural changes in the placental labyrinth of the rat with increesing geetetional age. J. Ultreetructure Resecroh 10: 2747, 1964. JOLLIE, W.P.: Rsdioautogrephic observations on variations in deoxyribonucleic acid synthesis in rat placenta with increasing gestational age. Am. J. Anat. 114: 161-171, 1984. k m o , K., SUOAYA, T.,Omsm, 5.and MIYNI, T.:' Electron microscopic ebudiea of placental and uterine tumors induced in rat. Acta Path. Jap. 26: 703-708, 1976. LAM~N, J.F., Emram,R.L.and BIB~UUNO, F. : Electron microscopy of human choriocarc1967. inoma transplanted into hamster liver. Am. J. Obet. & Gynec. 99: 11OQ-1124, Um, J.J.: Fibrinoid and the fetal mateml interface of the rat placenta. Anat. Rec.
166: 687404, 1970. 11. 1Kryaaa0~0, M., SUOAYA, T. and MATBUWTO, K.:
Brief communication; Conversion of 3beta-hydroxyp~-6-en-20-oneto progesterone by transplantable choriocarcinoma in rats. J. Natl. Cancer Inat. 52: 1369-1360, 1074. 12. Warn, M.: Experimental induction of choriowcinoma in rats. Gann 62: 66-66, 1971. E.W.: Study of induced malignant tumors of placental 13. S m m , S., GLASS,L.E. and PAOID, and uterine origii in the rat. II.Induced tumors and their pathogenesis with special reference to choriocercinoma. Am. J. Obst. & Gynec. 95: 660668, 1968. 14. STEIN-W~BLOWSKY, R.: Induction of a chorion-epitheliomatous tumors in the rat. Nature 186; 980, 1960. , 16. WISUMKI,G.B. and D ~ s YE.W.: Rec. 123: 33-63, 1966.
Electron microscopy of the placenta of the rat. Anat.
EXPERIMENTAL RAT CHORIOCARCINOMA
-An Electron Microscopic Study Kennichi KAKUDO Department of Pathology, Osaka University Mea'ical School (Received on April 15, 1976) Experimental choriocarcinomas of the rat were studied with electron microscopy and compared with the ultrastructure of rat trophoblasts at mid-and late-gestational stage. The choriocarcinoma numbered m-803 contained abundant cytoplasmic organellae and was quite similar to the trophospongial cell a t late- gestational stage. The m-801 closely resembled the trophospongial cell a t mid-gestational stage. The m-673, which has 3beta-ol dehydrogenase enzyme system," could not be studied sufficiently inspite of the examination of more than 30 blocks of epon embedded specimen, because of the degeneration and necrosis occurring in the specimens. ACTA PATH. JAP. 27: 41-50. 1977.
There is only a limited number of literatures on experimental choriocarcinoma of the rat.leJ8J4 The local application of chemical carcinogen in the placenta of pregnant To our rat had been reported to induce choriocarcinoma in a high incidence!J9 knowledge, there are no reports about spontaneously occurring choriocarcinomas in the rat, and there are no reported studies on the ultrastructure of choriocarcinoma of the rat. The present report deals with the studies on the ultrastructure of rat choriocarcinoma which were induced by M. MIYAMOTO and numbered as m-673, m-801, m803, comparing with rat trophoblasts of increasing gestational stage. Mater&Qls and
Methods
The three primary tumors of rat choriocarcinoma induced in Wistar pregnant rata were The experimental methods of induction of these tumors had obtained from Dr. M. MIYAMOTO. been described elsewhere (M. MIYAMOTO,1971)1* The animals were anesthetized with ether, the tumor specimens were surgically removed and fixed with 3% glutaraldehyde at 4°C (phosphate buffered a t pH 7.3) end postfixed with 1% osmium tetraoxide a t 4°C for electron microscopy. The specimens dehydrated in graded ethanol and embedded in epon. The ultrathin sections were stained with uranyl acetate end lead tartrate. The sections were examined with HU-I1B electron microscopy a t 75KV. The specimens of normal rat placenta of the 12th, IBth, and 20th gestational day were prepared by the same methods.
Obs&k Ultrastructural observations of rat choriocarcinoma were described briefly in a preceeding report! There are common ultrastructural features, such as, few
*2i
s-
Address: Department of Pathology, Osaka University Medical School, Osaka-shi, Kita-ku, Joan-oho 33, Japan. 530 41
42
EXPERIMENTAL RAT OHORIOOARCINOMA
Acta Path. Jap.
Fig. 1. Experimental rat choriocarcinoma m-803. The cell size is larger than the other two. The nuclear outline is 80 pleomorphic with nuclear invaginations that the tumor cell of m803 seems to be a multinucleated giant cell in electron microscope. I n the cytoplasm, there are many polyeomes, short segments of RER end round mitochondria with membranous flat crietae. Original magnification x 5,000, uranyl and lead tartrate.
27(1): 1977
K. KAKUDO
43
Fig. 2. Toluidine blue stained thick section of epon embedded material of rat choriocarcinoma m-803. There are many giant cells with pleomorphic nuclei, but there are no multinucleated giant cells. Original magnification x 400, toluidine blue.
desmosome-like attachments at cell surface and numerous free ribosomes, polysomes and rough-surfaced endoplasmic reticulum (RER) in cytoplasm, but there are much ultrastructural differences between the three rat choriocarcinomas of m-673, m-801 and m-803, as will be noted in the following observations. m803 Three blocks of epon embedded specimens of m-803 were examined for this study. The cell size is larger than the other two with occasional pleomorphic giant cells (Fig. 1) The nuclear outline is so pleomorphic with nuclear invaginations that the tumor cell appears as a multinucleated giant cell on electron microscope. But in toluidine blue thick section (Fig. 2), there is no syncitial type giant cells which are the characteristic feature of human choriocarcinoma. The tumor cells are relatively tightly arranged with few desmosome-like attachments. No microvilli are found on the cell surface. In the cytoplasm, there are many round mitochondrias with membranous flat cristae, polysomes, free ribo.somes and short segments of RER (Figs. 1, 3). Few tonofilamentlike fibers are found in the peripheral cytoplasm. The ultrastructural features of m-803 closely resemble those of trophospongial cell of late gestational stage. m-80 1
Four blocks of epon embedded specimens of m-801 were examined for this study. The tumor cells are relatively tightly arranged and form some desmosome-like
44
E X P m m T A L RAT OBORIOOAMXNOMA
A& Palh. Jap.
Fig. 3. Experimental rat choriocarcinoma m-803. There are few desmoeome-like attachmenta (arrow) between tumor calls. In the cytopleem, there are numeroua polysomea and few tonofilament-like fibers peripherally. Original magnification x 10,OOO, uranyl and lead tartrate.
27(1): 1977
K. KAKUDO
Fig. 4. Experimental rat choriocarcinoma m-801. There are many demosome-like attachments (arrow) between tumor cells. In the cytoplasm, the tumor cell is rich in polysomes and RER. The cell size of m-801 is smaller than that of 111-803. Nuclear invagination is rare. Original magnification x %OW, uranyl and lead tartrate.
attachments between tumor cells (Figs. 4, 5). No microvilli are found on the cell surface. In the cytoplasm, the tumor cells of m-801 are rich in free ribo.sonies, polysomes and RER, and are relatively poor in mitochondria. The tumor cells of m801 are poorly differentiated in development of cytoplasmic organella than ni-803 and closely resemble the trophospongial cell of mid-gestational stage. m-673 Careful study of more than 30 epon embedded blocks of m-673 failed to demonstrate apparent neoplastic epithelial cell nests, because the specimens of 11-673 obtained for the present study were fibrous mingled with degeneration and necrosis. The cells of m-673 demonstrated by electron microscopy are chiefly fibroblastic and surrounded by thick collagen fiber bundles. Few epithelioid cells with denmobsome-likeattachments are occassionally found and the cytoplasm of these cells are rich in polysomes and RER.
l4EpRRJ.lUNTAL RAT OHORIOOAIUJINOMA
Aeto Path. Jap.
Fig. 5. Experimental rat choriocarcinoma m-801. The cytoplasmic organella ie poorly developed except for ribosomee. Deernosome-like attschementa can be seen between tumor cells. Original magnification x lO,OOO, uranyl and lead tartrate.
DisCUSSiora
Spontaneous Occurrence of choriocarcinoma in the rat, and their ultrastructures have not been reported up to date. It is nessesary to compare experimental choriocarcinoma of the rat with normal trophoblasts of the rat ultrastructurally. Review of the ultrastructure of normal trophoblasts of rat placenta with increasing gestational stage is as follows. The rat gestational stage is conveniently divided into four stages in this report. The first is the preimplantational stage1 of 0 to 6th gestational day and the second is the formation of an ectoplacenta3 of 6 to 9th gestational day, which is excluded in this study because it is very difficult to demonstrate the trophoblasts ultrastructurally. The third is the mid-gestational stage of forming a labyrinth of 10th to 18th day and the fourth is the late-gestational stage of maturation and preterm of 19th to 2lst day. Although some of the details of structural organization of rat placenta still contain unsolved problems, the ultrastructure of the trophoblasts of the labyrinth and junctional
27(1): 1977
47
E. KhKUDO
Decidua baaalis
Giant cells
Trophospongial and glycogen cells
Fig. 6. Toluidine blue stained thick section of junctionel zone of normal rat placenta at 16th day. At the top, one can sea decidue beselis which is the maternal element. Note fetal tmphoblesta of trophoblestic gient cells (middle), trophospongial cells and glycogen cells (bottom). Originel magnification x 400, toluidine blue.
zone (basal zone, spongy zone, reticular zone) had been clearly described at mid-and late-gestational stage.*n6n'J6 The labyrinth is called hemotricorial and is composed of four layers, which are three trophoblastic layers and fetal endothelium with basement membrane.2 The junctional zone consists of at least three distinct trophoblastic elements histologically (Fig. 6), which are trophospongial cells (small basophilic cells), glycogen cells and trophoblastic giant cells. It is supposed that the trophospongial cells differentiated into glycogen cells and labyrinthine trophoblasts before the 18th gestattional day, after which all trophoblasts are mitotically inactive.' In addition to it, it is supposed that the trophospongial cells transform into giant cells,4 in other words, the primitive cell of all trophoblasts is the trophospongial cell. The ultrastructural features of these trophoblasts according to its increasing gestational stage had been reported minutdy as follows. The trophospongial cells of the 12th day are small, oval and poorly differentiated (Figs. 7, 8). The nuclear outline often appears to be pleomorphic, and mitosis is occasionally found. In the cytoplasm, the trophospongial
48
IXPMMIKENTAL BAT OHORIOOARCINOMA
A& Paih. Jap.
27(1): 1977
K. gdKUD0
49
cells contain numerous free ribosomes and polysomes, a few RER, ovoid mitochondria and lipoid droplets. In arrangment, the trophospongial cells seem to be epithelioid because they possess some desmosomes. The trophospongial cells of the 16th day are not so different from those of the 12th day as to cytoplasmic organella, but in arrangment they are somewhat looser than that of the 12th day. The trophospongial cells of the 20th day (late gestational stage) are much looser than those of the 12th and 16th day, and are surrounded by amorphous dense material.10 In the cytoplasm, the trophospongial cells of the 20th day are rich in organella, particularlly dilated RER and round mitochondria with membranous flat cristae. The development of RER is so high in degree that the cells vary in size and are somewhat larger than those of the 12th and 16th day. The trophoblastic giant cells of the 12th, 16th and 20th day are not so different in general. The cytoplasmic organellae of giant cells appear more highly differentiated than those of trophospongial cells. There are numerous polysomes, RER, G-olgi apparatus and phagosomes in the cytoplasm, many desmosomes at the cell surface and annulated lamellae in the large nucleus. The glycogen cells can be distinguished by vesicular and clear cytoplasm in light microscope. The cytoplasm contains abundant glycogen particles and a few Gal@ apparatus, RER and mitochondria. The cytoplasmic organellae of the glycogen cells of the 12th, 16th and 20th day are not 80 different in general. The present report suggests that the experimental choriocarcinoma numbered m803 ultrastructurally resembles the trophospongial cell of late getational stage and m801 also resembles the trophospongial cell of mid-gestational stage. It is supposed that m-803 is a well differentiated choriocarcinoma and m-801 a poorly differentiated choriocarcinoma derived from trophospongial cell which is assumed to be a primitive cell of all trophoblasts of the rat placenta. Though the ultrastructural features of m-673 were not fully examined electron microscopically, the epithelioid cells of m-673 is classified as a choriocarcinoma resembling the trophospongial cell of mid-gestational stage, for the time being. In comparison with human choriocarcinoma, rat choriocarcinoma differs greatly from that of human ultrastructurally. In human choriocarcinoma, there are syncytial trophoblastic type cell and cytotrophoblastic type cell". The former is a multinucleated giant cell, which possesses short microvilli and desmosomes at cell surface, and numerous phagosomes, dilated RER and polysomes in the cytoplasm. The latter is small and possesses desmosomes, many polysomes and short segments of RER. In experimental rat choriocarcinoma, there is only one type of cell which resembles a trophospongial cell at various gestational stages, and there is no resemblance to Fig. 7. The trophospongial cell of normal rat placenta at 12th day. Mitoaie is seen in lower left. The cytoplasmic organella is poorly developed except for ribosomes. Original magnification x 5,000, uranyl and lead tartrate. Fig. 8. The trophospongial cell of normal rat placenta at 20th day. There are amorphous dense material (A) at intercellar space end many deamosomea(arrow) between trophospongial cells. Dilated RER and round mitochondria with membraneom flat cristm are well developed in the cytoplaan. Original magnification x 6,000, uranyl and lead tartrate.
glycogen cell and trophoblastic giant cell. It is supposed that the difference might be due to the structural difference of human placenta and rat. A c k n u w W e : The author wishes to exprew his gratitude to Prof. T. M ~ Y ~ Wfor I his advice and support in this investigation, and ale0 to Dr. M. Mrynaamo for allowing us to use. his tumor specimens for the p m n t study. ReferencRp
1. ENDBBB, A.C. and , S.: A morphological analysis of the early implantation etagee in the rat. Am. J. Anat. 120: 186-226, 1967. 2. ENDBBB, A.C.: A comparative study of the h e structure of the trophoblset in several hemochorial placenta Am. J. Anat. 116: 2988,1966. J.W.: Morphological and physiological studies of the placenta in the albino 3. EV&BIUDT, rat. J. Exp. Zool. 70: 243-284, 1936. o R , Histological and fine structural obsewations on the placenta 4. DAVIES,J. and G L ~ ~ s ~S.R.:
6.
6.
7. 8.
9. 10.
of the rat. Part I. Organbation of the normal placenta. Part II. Changes after surgical removal of the fetus (fetectomp). Acta. Anat.169: W2-608, 1968. JOLLIID, W.P.: Fine structural changes in the junctional zone of the rat placenta with increasing gestational age. J. Ultraahcture Rseeech 12: 420-438, 1966. Jo-, W.P.: Fine structural changes in the placental labyrinth of the rat with increesing geetetional age. J. Ultreetructure Resecroh 10: 2747, 1964. JOLLIE, W.P.: Rsdioautogrephic observations on variations in deoxyribonucleic acid synthesis in rat placenta with increasing gestational age. Am. J. Anat. 114: 161-171, 1984. k m o , K., SUOAYA, T.,Omsm, 5.and MIYNI, T.:' Electron microscopic ebudiea of placental and uterine tumors induced in rat. Acta Path. Jap. 26: 703-708, 1976. LAM~N, J.F., Emram,R.L.and BIB~UUNO, F. : Electron microscopy of human choriocarc1967. inoma transplanted into hamster liver. Am. J. Obet. & Gynec. 99: 11OQ-1124, Um, J.J.: Fibrinoid and the fetal mateml interface of the rat placenta. Anat. Rec.
166: 687404, 1970. 11. 1Kryaaa0~0, M., SUOAYA, T. and MATBUWTO, K.:
Brief communication; Conversion of 3beta-hydroxyp~-6-en-20-oneto progesterone by transplantable choriocarcinoma in rats. J. Natl. Cancer Inat. 52: 1369-1360, 1074. 12. Warn, M.: Experimental induction of choriowcinoma in rats. Gann 62: 66-66, 1971. E.W.: Study of induced malignant tumors of placental 13. S m m , S., GLASS,L.E. and PAOID, and uterine origii in the rat. II.Induced tumors and their pathogenesis with special reference to choriocercinoma. Am. J. Obst. & Gynec. 95: 660668, 1968. 14. STEIN-W~BLOWSKY, R.: Induction of a chorion-epitheliomatous tumors in the rat. Nature 186; 980, 1960. , 16. WISUMKI,G.B. and D ~ s YE.W.: Rec. 123: 33-63, 1966.
Electron microscopy of the placenta of the rat. Anat.
