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1.
The initial segment of the caput epididymidis, the most proximal part of the rat epididymis, has specific functional characteristics. In the present study, the behavior of the epididymal epithelium from this region was evaluated after the exposure to a massive number of immature germ cells in the luminal fluid. The experimental release of immature germ cells from the seminiferous tubules was performed by injecting anti-microtubule compounds into the rete testis and the lumen of seminiferous tubules. Twenty-four hours after nocodazole or colchicine administration, a massive phagocytosis of immature spermatogenic cells, recognized as acrosin-positive structures, was easily observed in the epithelium of the initial segment of the epididymis assessed by light and electron microscopy. Immature germ cells were engulfed by epithelial cells, where most of them were found as cell debris at different stages of degradation. No signs of inflammation were observed either in the lumen or in the interstitium. The phagocytosis of immature germ cells was restricted to the epithelium of the initial segment of the epididymis, suggesting a role for this segment as the first selective barrier for the exclusion of abnormal gametes along the male genital tract.  相似文献   

2.
Adult male rats were administered the antiandrogen, cyproterone acetate, for 4, 8 or 12 weeks, and the histology and fine structure of the testis and several parts of the epididymis were studied. After treatment for 8 or 12 weeks, the testes of treated animals displayed a great reduction in the abundance of late spermatids. Necrotic cells, many of which were identified as cap-phase spermatids, were present in the seminiferous epithelium. Sertoli cells contained many large lipid droplets and lysosome-like structures with a content of cellular debris, including parts of spermatids. Leydig cells of treated rats were smaller than those of control animals at all the intervals studied. Sperm were absent from the lumen of the middle segment, or caput epididymidis, of severely affected specimens. In the terminal segment, or cauda epididymidis, the microscopic appearance varied in different regions. In the proximal part of the cauda epididymidis, the lumen was usually clear of sperm. The epithelium was tall and the light cells were very large and distended with many dense bodies resembling lysosomes. In contrast, in the distal part of the cauda epididymidis, the lumen was filled with sperm and debris, which appeared to be derived from germ cells. It is suggested that the light cells of the epididymal epithelium may have a role in clearing the lumen in the proximal part of the cauda epididymidis, in which they are particularly large and numerous. The results suggest that in the presence of cyproterone acetate, germ cells develop up to cap-phase spermatids and then begin to undergo degeneration and death. This alteration may have an important role in the antifertility effect of the drug, but changes in the epididymis may contribute also.  相似文献   

3.
The histology and fine structure of the testis, epididymis and sex accessory glands were studied in young adult male rats administered testosterone enanthate, 120 μg/100 g body weight, three times weekly for 4, 8, or 12 weeks. The weights of the testis and epididymis decreased, and animals treated for 11 weeks were infertile. Alterations were found in the seminiferous tubules of all rats treated for 8 or 12 weeks, including the presence of many degenerating germ cells and a-large decrease or absence of late spermatids. Study of different stages of the cycle of the seminiferous epithelium showed that the greatest number of degenerating germ cells, step 7 spermatids and pachytene primary spermatocytes, occurred at stages VII-VIII of the cycle. Some normal appearing spermatogonia, primary spermatocytes and early spermatids remained in most seminiferous tubules. Sertoli cells contained many lipid droplets and lysosome-like bodies, and degenerating cells were surrounded by Ser-toli cell cytoplasm. The Leydig cells of treated animals were greatly reduced in size. Sperm progressively disappeared from the lumen of the middle segment and proximal part of the terminal segment of the epididymis after treatment for 8 or 12 weeks. Changes in the middle segment also included the appearance of intraepithelial cavities containing debris, and the presence within the epithelium of phagocytic cells that resembled leukocytes. The lumen of the proximal part of the terminal segment was often collapsed, while in the distal part of the terminal segment, the lumen was filled with cellular debris and degenerating sperm. Organelles of the principal cells of the epididymal epithelium appeared to be qualitatively unaltered. The weight of the sex accessory glands remained close to normal, and the presence of normal ultrastructural features suggested that production of secretions continued.  相似文献   

4.
Young adult male rats were administered medroxyprogesterone (Provera, Upjohn) alone and in combination with testosterone, as has been done to inhibit male fertility. The histology and fine structure of several segments of the epididymis, the ventral prostate, and the seminal vesicle were studied at intervals after treatment for up to 16 weeks. The epididymides of treated animals weighed less than those of control rats. Microscopic alterations in the epididymis were similar in rats treated with Provera alone and in those animals that received Provera and testosterone, but the changes varied with the segment of the epididymis. In the middle segment in the caput epididymidis, the normally abundant luminal sperm were absent but the epithelium retained its normal ultrastructural features. In the terminal segment in the cauda epididymidis, different changes were observed in the proximal and distal portions. In the proximal cauda epididymidis, the lumen was small, irregular in outline, and virtually devoid of sperm. The light cells of the epididymal epithelium in the proximal cauda contained extremely large numbers of dense bodies resembling lysosomes, which occupied most of the supranuclear and basal cytoplasm. In contrast, in the distal part of the cauda epididymidis, the epithelium had a normal appearance but the lumen was filled with debris, sperm, and spherical masses of cytoplasm that were apparently derived from germ cells. It is suggested that the clearing of the lumen of the proximal cauda epididymidis may reflect the greater activity of light cells of the epididymal epithelium in that region. Although alterations in spermatogenesis may be most important in the antifertility effect of progestin and androgen, these alterations in epididymal sperm and epithelium may also play a role. The weights of the prostate and seminal vesicles of rats treated with Provera (1 mg/100 g/day) were greatly reduced compared to those of control rats. Although there was considerable variation, in many specimens treated with Provera alone the epithelium of the prostate showed a change from a columnar to a cuboidal or squamous shape, and there was a reduction in the size and abundance of organelles involved in the formation of secretions. The microscopic structure of the seminal vesicle of rats treated with Provera was less severely affected than the prostate. Although the seminal vesicle epithelium of Provera-treated rats was generally not as tall as in control animals, the cells possessed parallel cisternae of rough endoplasmic reticulum, secretory vacuoles, and an active-appearing Golgi apparatus, suggesting that they continued to be able to form secretions in the presence of Provera. The weights of the sex accessory glands were maintained at control levels by the administration of testosterone, 100 μg/100 g/day, along with the Provera. A normal fine structure was present in the epithelium of both the prostate and seminal vesicle of rats administered this amount of testosterone in addition to Provera. Lower doses of testosterone (15 or 30 μg/100 g/day) were insufficient to maintain normal weight or ultrastructure of the sex accessory glands in the presence of Provera.  相似文献   

5.
A previous study showed amastigote forms of Trypanosoma cruzi in the sex organs of male mice 15 days after inoculation. The purpose of the present work was to investigate the sequelae occurring in the male reproductive system during a later phase of Chagas' disease. Depleted germinal epithelium and release of immature germ cells into the tubular lumen were observed in the testis of chronic chagasic mice. The relative weights of the epididymis, vas deferens and seminal vesicle were significantly increased. Histological examination revealed a sharp thinning of the ductal and acinar walls. The results are discussed in terms of a neuromotor disturbance leading to sperm retention.  相似文献   

6.
Horseradish peroxidase introduced into the lumen of the rat epididymis was taken up by the columnar cells of the epithelium by five minutes and more so after longer periods. The apical cells and particularly the clear cells in the caput and cauda epididymis, respectively, showed significantly greater endocytotic activity than the principal cell in both locations. Within 14 days after castration, however, such differences in absorptive activity among the various cell types were essentially obscured because of increased endocytosis by the androgen-deficient principal cells. The results are discussed briefly in terms of the function of different epithelial cell types and secretory/absorptive activity in the epididymis.  相似文献   

7.
The ultrastructural pathology of the initial segment of the rat caput epididymidis was examined after oral administration of a single high dose of the antifertility compound α-chlorhydrin (U-5897) at time intervals ranging from two hours to nine days after treatment. At doses in excess of 30 mg/kg this compound produces a lesion specifically localized in the initial segment of the epididymis characterized by sloughing of the epithelium, which leads to obstruction of the lumen of the epididymal duct, spermatocoel and sperm granuloma formation and an ultimate occlusive fibrosis. In rats fed 140 mg/kg of U-5897 the first effects can be seen as early as two hours after treatment. Within 48 hours after treatment, the lumen of the greater part of the initial segment is filled with degenerating cells and debris which block further passage of sperm along the duct. The present study provides insight into the nature of the early events in the evolution of this epididymal lesion. Possible mechanisms of action of α-chlorhydrin are discussed.  相似文献   

8.
Horseradish peroxidase introduced into the lumen of the rat epididymis was taken up by the columnar cells of the epithelium by five minutes and more so after longer periods. The apical cells and particularly the clear cells in the caput and cauda epididymidis, respectively, showed significantly greater endocytotic activity than the principal cell in both locations. Within 14 days after castration, however, such differences in absorptive activity among the various cell types were essentially obscured because of increased endocytosis by the androgen-deficient principal cells. The results are discussed briefly in terms of the function of different epithelial cell types and secretory/absorptive activity in the epididymis.  相似文献   

9.
Male rats were subjected to 9-month-long exposure to ammonium fluoride. The performed evaluation covered the seminiferous epithelium and epididymis. The greatest changes in animals used in the experiment were observed in epididymis. A small number of spermatozoa were seen in the lumen of ductus epididymis, while in the epithelial cells there were increased phagocytic processes, providing a proof that injured reproductive cells were eliminated from the genital tract.  相似文献   

10.
The ultrastructure of the hamster efferent ducts and epididymis was studied and the results were correlated with previously published data on the composition of luminal fluid obtained by micropuncture. Samples of the efferent ducts and parts of the epididymis designated initial segment, caput, corpus, proximal cauda, distal cauda, and “epididymal vas” were prepared. The efferent ducts contained principal cells characterized by a profusion of apical vesicles and numerous very large vacuoles that were distributed throughout the cytoplasm. Ciliated cells had few vesicles and vacuoles. Occasional cells contained many particles resembling glycogen. In the epididymis, the following trends were observed. The height of the epithelium and the size of the principal cells declined from initial segment to distal cauda. Apical vesicles and vacuoles with a light content were extremely numerous in principal cells of the initial segment and decreased progressively in the more distal regions. In the initial segment, basal and perinuclear rough endoplasmic reticulum was abundant and was distended with a material that resembled newly synthesized protein. Further distally in the epididymis cisternae of the rough endoplasmic reticulum were narrow and contained little intracisternal material. Light cells containing many vesicles, vacuoles, and lysosome-like structures were very prominent in the caudal segments. The epithelium of the epididymal vas had features intermediate between cauda epididymidis and ductus deferens. The cytoplasmic droplet in luminal sperm began to migrate caudally between the caput and corpus epididymidis and reached the posterior extremity of the middle piece in the distal cauda. Some degenerating sperm were observed in the lumen of the distal segments of the epididymis. The abundance of cytoplasmic vesicles and vacuoles in principal cells of the efferent ducts and initial segment of the epididymis correlated with the site of greatest fluid absorption as determined by micropuncture studies, suggesting that these structures are involved in absorption of fluid from the lumen. Between the caput and distal cauda epididymal segments, where absorption of sodium and potassium but not of fluid occurred, there were few vesicles and vacuoles in principal cells, but the “light” cells were large and numerous and contained many vacuoles. The principal cells of the initial segment were best equipped with rough endoplasmic reticulum to synthesize a protein.  相似文献   

11.
The development of cell types and regional differences in the rat epididymis was studied in specimens of the initial, middle and terminal segments prepared at intervals between birth and postnatal day 94. The development of the epididymis was divided into three phases: (1) an undifferentiated period; (2) a period of differentiation, and (3) a phase of expansion. During the undifferentiated period, from birth to day 15, the epithelial cells had a uniform appearance. Halo cells, which are believed to be migratory leukocytes, appeared on day 14. The period of differentiation extended from day 16 to day 44. Slender, densely staining cells, termed narrow cells, appeared in the epithelium of all three segments on day 16, constituting the first evidence of differentiation of cell types in the epididymal epithelium per se. In addition to their shape and apical nuclei, the narrow cells were distinguished from other epithelial cells by the presence of cup-shaped apical vacuoles and mitochondria with tubular cristae. Principal cells and basal cells were identified on day 28, which also marked the first distinction of differences in epithelial height among the different segments. Narrow cells persisted into the adult in the initial segment. In the middle and terminal segments, however, narrow cells disappeared by day 35, when light cells made their appearance. The major event of the period of expansion, from day 45 to 3 months, was the appearance of sperm in the lumen between days 45 and 52. A model for differentiation of cell types in the epididymis is proposed and it is suggested that narrow cells are precursors to light cells in the middle and terminal segments. The development of ultrastructural features of adult cell types preceded the appearance of sperm in the lumen.  相似文献   

12.
The testes from 136 male cynomolgus monkeys were examined histopathologically in order to investigate the relationship between the development of spermatogenesis and testis weight, age, and body weight. At Grade 1 (immature), Sertoli cells and spermatogonia were the only cell classes in the testis. At Grade 2 (pre-puberty), no elongated spermatids were observed in the testis, although a few round spermatids and small lumen formation were observed. At Grade 3 (onset of puberty), all classes of germ cells were observed in the testis, although seminiferous tubule diameters and numbers of germ cells were small. Slight debris in the epididymis was observed in almost all animals. At Grade 4 (puberty), almost complete spermatogenesis was observed in the seminiferous tubules and it was possible to ascertain the spermatogenesis stage as described by Clermont, although tubule diameters and numbers of germ cells were small. There was less debris in the epididymis than at Grade 3. At Grade 5 (early adult), complete spermatogenesis was observed in the seminiferous tubules. At Grade 6 (adult), complete spermatogenesis in the seminiferous tubules and a moderate or large number of sperm in the epididymis were observed. Moreover, sperm analysis using ejaculated sperm was possible. Logistic regression analysis showed that testis weight is a good indicator of testicular maturity.  相似文献   

13.
The light and electron microscopic appearance of the various epithelial cells lining the efferent ducts and different regions of the epididymis were examined in rats on postnatal days 21, 39, 49, 56, and 90 to determine the role of androgens and/or spermatozoa, as well as other possible factors, on the structural differentiation of these cells. Five conclusions may be drawn from the observations made. First, on day 21 epithelial cells of all regions are structurally undifferentiated. Second, it was not until day 49 that nonciliated cells of the efferent ducts resembled those of adult animals, suggesting that more than one factor, such as androgens, testicular products, and/or spermatozoa, is needed for their full structural differentiation. Third, principal cells of the epididymis become structurally differentiated by day 39, i. e., these cells contained an elaborate Golgi apparatus, endoplasmic reticulum cisternae, and numerous 200–400 nm electron lucent secretory vesicles, as well as a full complement of endocytic organelles; this occurred in spite of the absence of spermatozoa in the epididymal lumen. The differentiation of these epididymal cells may be under the influence of androgens, which are known to be high at this time, but may also be due to specific secretions from Sertoli cells secreted directly into the efferent ducts. Fourth, clear cells of the cauda epididymidis are fully differentiated by day 39. The presence of degenerating germ cells in the lumen of the cauda epididymidis and various cellular debris, as well as high androgen levels, may be factors causing the differentiation of the cells of this region. Finally, clear cells of the corpus and cauda epididymidis only become fully differentiated by day 49, at a time when spermatozoa appear in the lumen, despite high levels of androgens at day 39; this observation indicates that the presence of spermatozoa in the lumen may be a necessary factor in causing their differentiation. Overall, these results suggest that a combination of different factors are necessary for the structural differentiation of the various epithelial cell types of the different regions of the epididymis. © 1992 Wiley-Liss, Inc.  相似文献   

14.
目的:探讨癫痫发作对雄性Wistar大鼠睾丸及附睾组织病理和超微结构的影响。方法:运用氯化锂一匹罗卡品建立Wistar雄性大鼠癫痫模型,取睾丸、附睾分别制片观察组织病理及超微结构的形态学改变。结果:光镜观察下,A组(造模成功组)及B组(造模不成功组)大鼠睾丸生精小管内各级生精细胞排列基本整齐,结构未见明显紊乱现象,但生精细胞层次呈不同程度的减少,睾丸生精小管管腔内精子数目减少,可见坏死脱落的生精细胞,睾丸间质结构缺如,间质细胞明显减少。附睾中,A组管壁柱状细胞,基细胞层次清晰,结构整齐,微绒毛排列整齐,但管腔中精子数目明显减少,有较多的非精子细胞成分。B组附睾管腔中精子数目未见明显下降,有时可见散在的生精细胞。电镜观察下,A组大鼠睾丸生精细胞细胞核明显畸形,线粒体肿胀,线粒体膜仍然完整,但脊消失,粗面内质网肿胀明显,精子头部细胞核清晰,顶体形态不规则,尾部“9*2+2”结构整齐,周围包绕的线粒体鞘明显肿胀,线粒体数目明显减少。B组中仍可见上述不同程度的损害表现,附睾中,A组及B组均可见处于同一层面的主细胞,细胞核未见明显异常,核周围可见大量溶酶体,同时核周内质网均处于明显肿胀状态。C组(正常对照组)鼠睾丸及附睾切片的光镜、电镜表现皆正常。结论:癫痫不同程度的发作可引起大鼠睾丸及附睾组织病理和超微结构不同程度的改变,进而造成了雄性Wistar大鼠生殖系统相关指标的改变。  相似文献   

15.
The light and electron microscopic appearance of the various epithelial cells lining the efferent ducts and different regions of the epididymis were examined in rats on postnatal days 21, 39, 49, 56, and 90 to determine the role of androgens and/or spermatozoa, as well as other possible factors, on the structural differentiation of these cells. Five conclusions may be drawn from the observations made. First, on day 21 epithelial cells of all regions are structurally undifferentiated. Second, it was not until day 49 that nonciliated cells of the efferent ducts resembled those of adult animals, suggesting that more than one factor, such as androgens, testicular products, and/or spermatozoa, is needed for their full structural differentiation. Third, principal cells of the epididymis become structurally differentiated by day 39, i.e., these cells contained an elaborate Golgi apparatus, endoplasmic reticulum cisternae, and numerous 200-400 nm electron lucent secretory vesicles, as well as a full complement of endocytic organelles; this occurred in spite of the absence of spermatozoa in the epididymal lumen. The differentiation of these epididymal cells may be under the influence of androgens, which are known to be high at this time, but may also be due to specific secretions from Sertoli cells secreted directly into the efferent ducts. Fourth, clear cells of the cauda epididymidis are fully differentiated by day 39. The presence of degenerating germ cells in the lumen of the cauda epididymidis and various cellular debris, as well as high androgen levels, may be factors causing the differentiation of the cells of this region. Finally, clear cells of the corpus and cauda epididymidis only become fully differentiated by day 49, at a time when spermatozoa appear in the lumen, despite high levels of androgens at day 39; this observation indicates that the presence of spermatozoa in the lumen may be a necessary factor in causing their differentiation. Overall, these results suggest that a combination of different factors are necessary for the structural differentiation of the various epithelial cell types of the different regions of the epididymis.  相似文献   

16.
The control of the secretory cell cycle by estradiol and progesterone in the oviduct of the cat was studied using light and electron microscopy. The epithelium in ovariectomized animals was cuboidal with no evidence of secretory activity. Estradiol treatment induced hypertrophy, hyperplasia, and the differentiation of both secretory and ciliated cells. Differentiation of the secretory cell included the development of an extensive area of basal rough endoplasmic reticulum and a large supranuclear Golgi region. Apical secretory granules were already present after 3 days of estradiol treatment, and after 4 to 5 days maximum hypertrophy and differentiation had occurred. Most cells contained several apical electron-dense granules; however, no large accumulation of granules in any one cell was ever observed. Occasional release of secretory product by exocytosis occurred during chronic treatment with estradiol. Rapid elevation of the serum levels of estradiol or progesterone by means of IV injection did not enhance exocytosis or result in any ultrastructural alterations. The chronic administration of progesterone to estradiol-primed animals resulted in rapid cell atrophy, dedifferentiation, and death (apoptosis) within the epithelium of the oviduct. Secretory granules were no longer observed after 2 days of estradiol and progesterone treatment, and after 7 days the epithelium was approximately the same height as that measured in ovariectomized animals. These data illustrate that estradiol induces the differentiation and maintains the mature state of the secretory cell within the oviductal epithelium of the cat, and that progesterone has an immediate antiestrogenic effect on these cells. This study also suggests that the secretory product is released gradually, as the granules form and mature during chronic estradiol administration.  相似文献   

17.
Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microscopy to confirm that the epididymis is a definitive target of gossypol. Although exposure to gossypol from weaning through puberty caused a significant decrease in daily sperm production, as well as in the concentration of sperm in the epididymis, serum testosterone levels and reproductive organ weights were not altered. In gossypol treated rats, sperm morphology was compromised severely, but the epithelium in testis and epididymis appeared morphologically normal. Ultrastructural examination revealed that round structures, present only in gossypol exposed males, represented: (1) principal cells exfoliated from the epididymal epithelium; (2) epididymal epithelial cell cytoplasm containing degenerating sperm; and (3) degenerating epithelial cells, consisting of vesicles and particles of different sizes, forms and densities. Taken together, the data confirm that gossypol targets the epididymis, disturbing both the structure and function of this organ, and presumably disrupts sperm maturation.  相似文献   

18.
To determinate what damage occurred in the bile ducts of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 11 patients were studied with the light and electron microscope and compared with normal material. Thick sections (1 micrometer) showed light and dark cells in biliary epithelium and lipofuscin granules. At the ultrastructural level these were confirmed. The lumen of the bile ducts contained debris. The microvilli were decreased in number and damaged forms appeared. Damage to the biliary epithelial mitochondria was widespread and there were foci of intracellular oedema. The Golgi apparatus was hypertrophied and dilated. Atrophic cells were seen. The lateral intercellular spaces were dilated and contained debris and the basement membrane showed zones of duplication. Similar changes were found in the ducts of Hering.  相似文献   

19.
Young adult male rats were treated with clomiphene citrate, a non-steroidal inhibitor of gonadotropin release in the rat. They were administered 2.5, 3.5, or 5.0 mg/100g/day for intervals up to 12 weeks. The weights of the sex accessory glands were less than those of control rats, and decreased with increasing dose and length of treatment. At the longer intervals, the weights of the testis and epididymis were also less than those of control animals. Microscopic alterations in the testis included a scarcity or even absence of late spermatids, the presence of necrotic cap-phase spermatids, and accumulation of lipid droplets and large lysosome-like structures in Sertoli cells. In rats treated for the longest interval, 12 weeks, testicular changes were even more extensive; degenerating primary spermatocytes were observed, and in one rat germ cells were virtually completely absent and the seminiferous tubules were occupied by Sertoli cells. The Leydig cells of treated animals were smaller than those of normal or control rats. Sperm were absent from the lumen of the caput epididymidis in most specimens. Although the epithelium of the caput appeared reduced in height in some samples, ultrastructural changes in cellular organelles were not detected. In most specimens of the cauda epididymidis, the lumen was small, irregularly shaped, and lacking in sperm. Light cells were prominent in the epithelium by virtue of their content of many apical vacuoles and dense granules. In some specimens of the distal cauda epididymidis, the duct had a circular profile and the lumen contained round cells and debris. The seminal vesicle and the ventral prostate were greatly suppressed. The normally tall columnar epithelia were reduced to a low columnar or cuboidal shape. Especially at the longer treatment intervals, the normally abundant rough endoplasmic reticulum was sparse, and in some samples secretory vacuoles were absent. The possible mechanism of production of these morphological changes is discussed, and the results are compared with those following treatment with other antifertility agents, including cyproterone acetate, a progestin, and a progestin-androgen regimen.  相似文献   

20.
We examined the effects of trichloroethylene (TCE) on the bronchiolar epithelium of mouse lung, using scanning electron microscopy. The lesion elicited by TCE involved predominantly the nonciliated Clara cells of the bronchiolar epithelium. Although there was slight loss of cilia and the mucosal surface exhibited increased deposits of debris throughout the period the tissues were observed, the ciliated cells appeared relatively uninjured. At 24 h following the intraperitoneal administration of TCE (2000 mg/kg) the Clara cells of the bronchiolar epithelium were irregularly distributed on the mucosal surface and reduced in number, indicating loss of cells by exfoliation. The remaining Clara cells appeared deformed and collapsed. This cell population was markedly reduced by seven days after TCE exposure, and the bulging apices characteristic of this cell type were virtually absent, resulting in a flattened epithelial lining. By 15 and 30 days after TCE, reparative processes were evident and micronodules consisting of multiple Clara cells protruded into the airway lumen. The administration of TCE to mice causes severe morphological damage to Clara cells of the bronchiolar epithelium which persists for at least 60 days after chemical exposure.  相似文献   

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