الفهرس 
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Abstract
The testis is mixed gland (exocrine and endocrine). The exocrine portion consists of a series of highly coiled seminiferous tubules that produce sperms (spermatogenesis). The endocrine portion consists of specialized cells called interstitial cells (Leydig cells) that secrete testosterone.
Depression is a chronic recurrent mood disorder that affects both economic and social functions worldwide. According to the World Health Organization, it will be the second leading contributor to the global burden of disease, calculated for all ages and both sexes by the year 2020. Most studies on fluoxetine showed that this drug caused significant structural changes of testicular tissue and sex hormones in male rats
Fluoxetine is a selective serotonin reuptake inhibitor drug (SSRI), important in the treatment of neurological diseases, such as depression, obsessive-compulsive disorder and bulimia nervosa. Fluoxetine entered the pharmaceutical market in America in 1987, and since then, it has had the highest prescription rate as antidepressant by psychiatrists
Omega-3 is essential, polyunsaturated fatty acids i.e. they cannot be synthesized in vivo. In diet, large quantities are found naturally in fish oil, flaxseed and some nuts. Omega-3 has anti-inflammatory and antioxidant effects.
This work was designed to evaluate the possible protective effect of Omega-3 on testicular tissue damage induced by antidepressant drug (Fluoxetine), in adult male albino rats, and the possible recovery after cessation of treatment.
Materials and methods Fifty adult male albino rats weighing 190-200 gms used in this study.
Animals were randomly divided into 4groups: group I (Control): 10 rats half of them received corn oil ”vehicle of Omega 3”, the other half received distilled water ”vehicle of Fluoxetine” orally by gavage once daily for 4 weeks. group II (Omega3- treated): 10 rats were administered 400 mg/kg /day of Omega-3 dissolved in corn oil orally by gavage once daily for 4 weeks. group III 20 rats further subdivided into 2 equal subgroups: Subgroup IIIa (Fluoxetine treated): received Fluoxetine (10 mg/kg /day) dissolved in distilled water orally by gavage once daily for 4weeks. Subgroup IIIb (Fluoxetine arrested): were administered Fluoxetine orally for 4 weeks as subgroup IIIa, then left untreated for further 4 weeks. group IV (Fluoxetine and Omega-3 treated): 10 rats received combination of Fluoxetine (10 mg/kg /day) and Omega-3 (400 mg/kg /day) orally by gavage once daily for 4weeks. B-Methods: At the end of the experiment, animals were scarified and weighted. The testes of all groups were dissected out and their weights were recorded. The tissues were prepared for stained with hematoxylin and eosin stain (Hx. &E.), Masson Trichome (MT) and Periodic Acid Schiff’s reaction (PAS) stain. Immunohistochemical stainning was performed by caspase-3, Proliferating Cell Nuclear Antigen (PCNA) and androgen receptors (AR). The number of PCNA) immunopositive cells in in each seminiferous tubule was counted. Data were collected for statistical analysis Results:
General result
Animals in groups I, II, IV were in good general condition and gain weight with no mortality. In contrast animals of Fluoxetine treated subgroup IIIa were weak and had loss of appetite & weight with no mortality. However, the clinical manifestations started to improve after stopping Fluoxetine administration in subgroup
Results
Histological and immunohistochemical results
group I (Control): Examination of H&E stained sections from control animals showed that the testicular parenchyma was formed of densely packed seminiferous tubules with rounded, regular outline and stratified germinal lining. These tubules were enclosed by a connective tissue capsule. The germinal epithelium was formed of spermatogonia, primary spermatocytes, spermatids and Sertoli cells. Primary spermatocytes were the largest one seen within the seminiferous tubules and some showed mitotic figures. Spermatids were small cells rounded or elongated arranged in 2 to 4 rows lying close to the lumen of the tubules. Sertoli cells were detected on the basement membrane between the spermatogenic cells. They were columnar cells with irregular outlines. Their nuclei tend to be triangular. The myoid cells were arranged outside the basal lamina. The interstitium contained clusters of interstitial Leydig cells with acidophilic cytoplasm. Normal distribution of minimal collagen fibers in the testicular capsule, basal lamina and interstitial tissues were detected by MT stain. PAS stained section showed moderate reaction in basal lamina of tubules.
Immunohistochemical stained sections of the control group revealed negative caspase-3 immunoexpression, positive PCNA immunostaining (deep
brown nuclear reaction) in all nuclei of basal germ cells and positive Androgen receptor immunoexpression. It appeared as brown nuclear staining of the interstitial cells, myoid cell and some sertoli cells.
group II: (Omega-3 treated): Sections of this group showed normal histological features nearly similar to control group.
Subgroup IIIa: (Fluoxetine treated): Fluoxetine induced variable degrees of tubular affection in the form of distorted seminiferous tubules, cellular disorganization, germ cells sloughing and cytoplasmic vacuolation. The tubules were surrounded by thick irregular basal lamina. The lumen of tubules contained few spermatozoa. Some germ cells had deeply stained pyknotic nuclei. Acidophilic hyaline streaks were extended between the degenerated spermatogenic cells. The inter-tubular space appears wide containing degenerated distorted Leydig cells and congested dilated interstitial blood vessels. Acidophilic hyaline material and vacuolations were present in most of the interstitial spaces. There was marked increase of the collagen fibers deposition in the capsule, basal lamina and interstitium. Very strong PAS reaction in the basal lamina, inter-tubular space and around blood vessels was detected. Immunohistochemically, Fluoxetine treatment induced marked increase in cytoplasmic expression of caspase-3, decrease in the mean number of PCNA positive immunostaining germ cells and negative immunoexpression of androgen receptor.
Subgroup IIIb: (Fluoxetine arrested):
After arrest of Fluoxetine treatment there were partial improvements. The testis of this group still contained distorted seminiferous tubules. This group still showed few cells with intense caspase-3 expression, positive PCNA immunostaining in some germ cells and weak androgen receptor.
group IV: (Fluoxetine and Omega-3 treated):
Marked improvement was observed in the examination of testes of this group. Most tubules were more or less similar to those of control and they were lined by normal arrangement of spermatogenic cells. But some cells had vacuolated cytoplasm. The inter-tubular space remained wide and contained acidophilic material. Moderate collagen fibers deposition and moderate PAS reactions were detected. This group showed improved immunohistological results nearly similar to control.
Statistical results:
The animal body and testis weight:
The mean body and testis weight of Fluoxetine treated Subgroup IIIa showed highly significant decrease (p value<0.001), while that of recovery Subgroup IIIb showed significant decrease (p value<0.05) versus to control.
The mean number of positive PCNA cells
The mean number of positive PCNA cells of Fluoxetine treated subgroup IIIa showed highly significant decrease (p value<0.001). While that of recovery Subgroup IIIb showed significant decrease (p value<0.05) compared to control.