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Revista chilena de anatomía

Print version ISSN 0716-9868

Rev. chil. anat. vol.17 n.2 Temuco  

http://dx.doi.org/10.4067/S0716-98681999000200005 

ULTRASTRUCTURAL OBSERVATIONS OF THE DORSAL LOBE OF THE
PROSTATE OF RATS (Rattus norvegicus) SUBMITTED TO EXPERIMENTAL
CHRONIC ALCOHOL INGESTION

OBSERVACIONES ULTRAESTRUCTURALES DEL LOBULO DORSAL DE LA
PROSTATA DE RATAS (Rattus norvegicus) SOMETIDAS A LA INGESTION
EXPERIMENTAL CRONICA DE ALCOHOL

* P. J. Garcia
** V. H. A. Cagnon
* W. Mello Jr.

***

Martinez, M.
*

Martinez, F. E.

* Department of Anatomy - Institute of Bioscience - UNESP - Botucatu, Brazil.
** Department of Anatomy - Institute of Biology - UNICAMP - Brazil.
*** Department of Morphology and Pathology - UFSCar, São Carlos, Brazil.
Grant 301.988/88-9 CNPq, Brazil.

SUMMARY: The problems related to the abusive consumption of alcoholic beverages are one of the most discussed public health concerns. The morphological and functional alterations caused by chronic ingestion of alcohol in the testes and accessory sex organ have been extensively studied both in man and in laboratory animals. The aim of this work was to examine the possibility of morphological changes in the secretory epithelium of the dorsal lobe of the prostate in rats submitted to chronic alcohol ingestion. Adults rats in the experimental group were divided into treatment periods of 60, 120, 180, 240 and 300 days, when they received only sugar cane brandy at 30º GL (30% v/v) to drink and were fed Purina rat chow ad libitum. At the end of each treatment period, four rats of each group were anesthetized by ether inhalation and perfused with 2,5% glutaraldehyde and fragments of the dorsal lobe were removed and processed for electron microscopy. The results demonstrated a general reduction of the cytoplasm and of the size of the granular endoplasmic reticulum, and whorl formation consisting of concentric membranes in the apical region of the secretory epithelial cells of the dorsal lobe. Chronic alcohol ingestion had deleterious effects on the secretory epithelial cells of the prostate dorsal lobe after the different treatment periods.

KEY WORDS: 1. Alcohol; 2. Prostate; 3. Ultrastructural; 4. Anatomy; 5. Rattus norvegicus.

INTRODUCTION

Alcoholism is considered to be the first chronic disease whose course has been found to be affected by genetic, psychosocial and environmental factors MADDEN (1993). Alcohol has numerous deleterious effects on health both in young and older individuals SPECKENS et al. (1991). Studies conducted on students at the University of California have revealed a significant increase in alcoholic drink consumption and in the problems due to alcohol ingestion over the last 12 years SCHUCKIT et al. (1994). Experimental and clinical studies using different methodologies have demonstrated that prolonged alcohol intoxication contributes to disorders in the activity of the hypothalamus-pituitary-gonadal axis in addition to having a direct toxic effect on the structure and function of the testis SEMCZUK & RZESZOWSKA (1981). The hypoandrogenism caused by alcohol is responsible for reduced sexual activity and impotence, in addition to causing changes in the biochemical composition of semen SEMCZUK & RZESZOWSKA. Men considered to be chronic alcoholics present reduced ejaculate volumes and loss of sperm motilty BRZEK (1987). VAN THIEL & LESTER (1979) and VAN THIEL (1983) observed that chronic alcoholism provokes morphological and physiological changes not only in the testis but also in the accessory sex glands.

MARTINEZ et al. (1993), studying rats submitted to experimental chronic alcoholism, observed epithelial cells of the ventral lobe of the prostate in a phase of degeneration, CAGNON et al. (1996) observed marked atrophy of the cisterns of the granular endoplasmic reticulum of secretory epithelial cells of the coagulation gland of rats in the presence of alcohol ingestion.

The accessory sex glands are essential for the maintenance of fertility in different species CHOW & W.S.O. (1989). The prostate is a complex gland formed by three pairs of lobes: the ventral, dorsal and lateral lobes distributed around the male urethra in rodents JESIK et al. (1982). The prostate gland depends on androgen for growth, differentiation, secretion and maintenance of morphology DAVIES & EATON (1991). In rodents, the three lobes of the prostate present differences in morphology, secretion product and hormonal responce PRICE & WILLIAM-ASHMAN (1961); DAHL & KJAERHEIN (1973); JESIK et al.; CUNHA et al. (1987); PRINS (1989); DAVIES & EATON (1991); COSTELLO & FRANKLIN (1994). Ultrastructurally, the dorsal lobe of the prostate is characterized by dilatation of the cisterns of the granular endoplasmic reticulum DAHL et al. (1973).

In a survey of the literature we did not detect any study on the influence of alcohol on the secretory epithelium of the dorsal lobe of the rat prostate. Thus, the objetive of the present study was to determine the possible morphological changes occurring in the secretory epithelium of the dorsal lobe of the prostate during chronic alcohol ingestion, in order to contribute to the elucidation of questions in this area.




Fig. 1. Electronmicrographs of cells of the secretory epithelium of the dorsal lobe of the prostate of control rats after 240 days of treatment. 1A) Simple epithelium. Columnar cells. Basal nucleus (N). Mitochondria dispersed throughout the cytoplasm. Developed Golgi apparatus (asterisk). Dilated cisterns of the granular endoplasmic reticulum (GER). Microvilli cover the surface of the cell facing the lumen. Lumen (L). Basal lamina (arrow). X 6.500.
1B) Basal region. Basal nucleus (N). Dilated cisterns of the granular endoplasmic reticulum (GER). Possible lysosomes (L). X 13.000.

MATERIAL AND METHOD

A total of 40 adult rats (Rattus norvegicus) of the same age were divided into two groups. The control group received water and the alcoholic group 30% (v/) sugar cane brandy. Before the beginning of treatment, increasing doses of brandy were administered at the dilution sale of 10º and 20º Gay Lussac (GL) for one week each until 30º GL were reached. Gradual alcohol administration was used to adapt the animals to the experimental model. The animals were sacrificed after 60, 120, 180, 240 and 300 days of treatment in order to determine the relationship of alcohol ingestion with time.

In the alcoholism model used, alcohol was administered as the only fluid available to the animals. The animals of both groups received the same solid diet (Purina ration) ad libitum. Fluid and solid consumption was measured weekly in both groups.

After the end of each treatment time, four animals from each group (control and alcoholic) were anesthetized with ethyl ether, weighed and perfused with 2.5% glutaraldehyde in 0.1 M phosphate buffer through the left ventricle of the heart. The dorsal lobe of the prostate was collected and routinely processed for transmission electron microscopy (TEM). Selected sections were then examined and photographed with a Philips EM 301 electron microscope.

RESULTS

Control group. The secretory epithelium of the dorsal prostate was characterized by columnar cells, a nucleus of basal localization with decondensed chromatin and a clearly visible nucleolus. The Golgi apparatus was located in the supranuclear region of the cytoplasm. Mitochondria were visible throughout the cytoplasm. Secretion granules were absent but vacuoles containing a secretion product of floccular appearance were observed (Fig. 1A). The cisterns of the granular endoplasmic reticulum were dilated in the basal region of the cytoplasm (Fig. 1B). Microvilli were detected on the cell surface, facing the lumen. The stroma was formed of fibrous and muscular connective tissue (Fig. 1B).

Alcoholic group. Morphological alterations of the cytoplasmic organelles were detected after 120, 180, 240 and 300 days of treatment. Howewer, no ultrastructural modifications were observed after 60 days of treatment. A marked reduction occurred in the cytoplasm of the secretory epithelial cells of the dorsal lobe of the prostate. The cells were atrophied, with a basally located nucleus and a dented contour. No nuclear inclusions were observed at any of the times of treatment studied. The cisterns of the granular endoplasmic reticulum showed a considerable reduction in area (Figs. 2A,B and 3A). Concentric formations possibly consisting of cytoplasmic portions were observed in the apical and supranuclear cytoplasm (Fig. 3B). Mitochondria were clearly visible throughout the cell cytoplasm, as also observed in the controls. The stroma of the secretory epithelial cells was unchanged and was similar to that of the control group (Figs. 2B and 3A).





Fig. 2. Electronmicrographs of cells of the secretory epithelium of the dorsal lobe of the prostate of alcoholic rats after 120 days of treatment. 2A) Atrophied simple epithelium, cuboidal cells with the basal nucleus (N) presenting dents. Mitochondria dispersed throughout the cytoplasm. The Golgi apparatus is observed in the supranuclear and apical cytoplasm (asterisk), together with vacuoles containig material of low electron density. Atrophied cisterns of the granular endoplasmic reticulum (GER) in the basal cytoplasm. Microvilli on the surface of the lumen. Basal lamina (Arrow). The stroma presents collagen fibers and smooth muscle. X 5.000.
2B) Basal region. Nucleus (N) with a clearly visible nucleolus. Atrophied cisterns of the granular endoplasmic reticulum (GER). Possible lysosmes (L). Clearly visible basal lamina (arrow). X 13.000.

DISCUSSION

Several investigators have studied the toxic effect of alcohol on the accessory sex glands, especially the ventral lobe of the prostate and the seminal vesicle of rodents.

VAN THIEL et al. (1975) observed absence of libido and loss of development of accessory sex organs, the prostate in particular, in chronic alcoholic men. SEMCZUK & RZESZOWSKA administered 40% ethyl alcohol to adult male rats at a daily dose of 3 g/kg injected directly into the stomach and observed loss of seminal vesicle and prostate mass compared to the control. KLASSUN & PERSAUD (1984) studied rats treated with alcohol by the oral route and observed a reduction in seminal vesicle mass and epithelial degeneration. WILLIS et al. (1983) worked with mice treated with 6% ethanol (v/v) for periods of 5, 10 and 20 weeks and observed a reduction of accessory sex organ mass. MARTINEZ et al. treated rats with sugar cane brandy at 35º GL by the oral route for periods of 45, 90 and 135 days and observed a significant decrease in body mass as well as in seminal vesicle and prostate lobe mass. In addition, they characterized morphological changes in the ventral lobe of the prostate compared to the control group. CAGNON et al. (1996) observed a reduction of the cisterns of the granular endoplasmic reticulum as well as nuclear changes in the cells of the secretory epithelium of the coagulation gland of chronic alcoholic rats. CAGNON et al. (1998) observed atrophy of the epithelium and accumulation of lipid droplets in the lateral lobe of the prostate of rats treated with 30% brandy (v/v).





Fig. 3. Electronmicrographs of cells of the secretory epithelium of the dorsal lobe of the prostate of alcoholic rats after 180 days of treatment. 3A) Atrophied simple epithelium and cuboidal cells with a basal nucleus (N) of irregular contour. Clearly visible Golgi apparatus and vacuoles containig material of low electron density are observed in the supranuclear and apical regions. Atrophied cisterns in the basal cytoplasm. Microvilli on the luminal surface. Lumen (L). Basal lamina (Arrow). X 6.500.
3B) Apical region. Nucleus (N). Cistern of the granular endoplasmic reticulum (GER). Mitochondria. Circular formations (CF). X 21.000

In the present study, atrophy of the epithelial cells of the dorsal lobe of the prostate and a significant reduction of the cisterns of the granular endoplasmic reticulum were observed after 120, 180, 240 and 300 of administration of 30% (v/v) brandy. Thus, a toxic effect of alcohol on the secretory epithelium of the dorsal prostate was observed. No significant changes in the different cell organelles were observed after 60 days. Possibly, the endocrine changes due to disequilibrium of the hypothalamus-pituitary-gonadal axis and leading to reduced testosterone secretion did not affect the epithelium of the dorsal prostate at the beginning of the experiment. This fact may be explained by the differential andogen dependence of the various prostate lobes. A non-hormonal factor may also participate in the control of epithelial activity. According to KIPLESUND et al. (1988), the ventral and lateral lobes are more sensitive to androgen action than the coagulation gland and the dorsal lobe of the prostate. Doubts persist about the etiology of the action of alcohol on prostate cells. Chronic exposure to ethanol has been reported to cause functional disorders of the hypothalamus-pituitary-gonadal axis, resulting in low testosterone levels LLOYD & WILLIAMS (1948); GALVAO TELES et al. (1973); VAN THIEL et al. (1974); GORDON et al. (1976) and CICERO & BADGER (1977).

A direct effect of alcohol on the synthesis of testicular testosterone has also been observed ELLINGBOE & CAROLE (1979); RIVIER & VALE (1983); BANNISTER & LOVOSKY (1987); ANDERSON et al. (1989) and SAXENA et al. (1990). VAN THIEL (1983) considered alcohol to be a direct gonadal toxin on the testis and also acting indirectly on the hypothalamus-pituitary-gonadal axis.

Based on the occurrence of the toxic effects of alcohol on male gonads, we may infer that alcohol acts both indirectly and directly on the secretory epithelium of the dorsal lobe of the prostate. Alcohol has a harmful effect on the cells of the dorsal prostate, modifying the mechanism of secretion and contributing to reduced fertility, as also observed in the ventral and lateral lobes of the prostate of rodents.

RESUMEN: Los problemas relacionados al consumo abusivo de bebidas alcohólicas, son una de las preocupaciones de salud pública más discutidas. Se han estudiado las alteraciones morfológicas y funcionales causadas por ingestión crónica de alcohol en los testículos y órganos sexuales accesorios de los hombres y de los animales de laboratorio.

El objetivo de este trabajo fue examinar los eventuales cambios morfológicos en el epitelio secretorio del lóbulo dorsal de la próstata, en ratas sometidas a la ingestión crónica de alcohol.

Las ratas adultas en el grupo experimental fueron divididas según los períodos del tratamiento de 60, 120, 180, 240 y 300 días, recibiendo para beber sólo alcohol de caña de azúcar de 30º (30% v/v) y fueron alimentadas con ración de Purina a voluntad.

Al final de cada período de tratamiento, cuatro ratas de cada grupo fueron anestesiadas por inhalación de éter y perfundidas con 2,5% glutaraldeido y fragmentos del lóbulo dorsal fueron removidos y procesados para la microscopía electrónica.

Los resultados demostraron a nivel celular reducción general del citoplasma y del retículo endoplasmático granular, así como también formación circular que consiste en membranas concéntricas en la región apical de las células epiteliales secretorias del lóbulo dorsal.

La ingestión crónica del alcohol tuvo efectos deletéreos en las células epiteliales secretoras del lóbulo dorsal de la próstata, después de los diferentes períodos del tratamiento.

PALABRAS CLAVE: 1. Alcohol; 2. Próstata; 3. Ultraestructura; 4. Anatomía; 5. Rattus norvegicus.

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Dirección para correspondencia:
Prof. Dra. Valéria H. A. Cagnon
Departmento de Anatomia
Instituto de Biologia
UNICAMP
CEP 13083-970
Cidade Universitária «Zeferino Vaz»
Campinas, SP
Brasil
Teléfono 55(019)7887391
Fax: 55(019)2434274
Email: quitete@uol.com.br

Recibido : 07-10-1999
Aceptado: 15-11-1999

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