scholarly journals Histological and immunohistochemical study of cyclophosphamide effect on adult rat testis

Author(s):  
Hoda H. Anan ◽  
Nashwa S. Wahba ◽  
Maha A. Abdallah ◽  
Dalia A. Mohamed

<p class="abstract"><strong>Background:</strong> Nowadays, cyclophosphamide is widely used as anticancer and immunosuppressive agent in various drug regimens in many diseases and in young and old age. The aim of this research is to study the possible histological changes that may occur in the testes of adult male albino rats as a result of chronic exposure to cyclophosphamide and the prognosis of this effect.</p><p class="abstract"><strong>Methods:</strong> Thirty healthy adult male albino rats were used in this study.  They were equally divided into three groups; a control, an experimental and a withdrawal groups. The Animals of the experimental group were treated with daily dose of 5 mg/ kg cyclophosphamide orally for successive 28 days. Animals of the withdrawal group were left without treatment and sacrificed after 28 days from the last dose of cyclophosphamide.  At the time of sacrifice, all animals were anesthetized by ether inhalation and their testes were dissected out carefully and processed for light and electron microscope examinations<span lang="EN-IN">. </span><span lang="EN-IN"> </span></p><p class="abstract"><strong>Results:</strong> Testes of the cyclophosphamide treated group revealed presence of many distorted shrunken seminiferous tubules which appeared with marked reduction in the thickness of the epithelium and wide lumina. Many germ cells with deeply stained nuclei, giant cells in mitosis and intracellular vacuoles were observed. Cross sections in mid pieces of sperms showed marked affection of axoneme, fibrous sheath and mitochondrial sheath. The cytoplasm of the Leydig cells contained mitochondria, dilated SER, Golgi cisternae and RER. Testes of the withdrawal group showed that the seminiferous tubules still had reduced height of their epithelium with wide intercellular spaces. Abnormal stratification and destructed germinal epithelium were evident with desquamated germ cells. Cross sections of mid pieces of the sperms showed distorted axoneme and swollen mitochondrial sheath. The cytoplasm of leydig cells contained many electron dense granules, RER, many dilated SER and mitochondria.</p><p class="abstract"><strong>Conclusions:</strong> Chronic cyclophosphamide treatment not only produced serious histological changes of the testis but also in its serological parameter. These changes persisted after cessation of cyclophosphamide administration which indicates the cumulative irreversible toxic effect of cyclophosphamide. So, it is advisable to avoid the usage of cyclophosphamide as possible especially in young patients<span lang="EN-IN">. </span></p><p class="abstract"> </p>

2017 ◽  
Vol 23 (2) ◽  
Author(s):  
Rubina Iqbal ◽  
Saud Iqbal ◽  
Iram Atta

AbstractObjectives:  The objective of this research work was to observe the testicular morphological changes produced by fluoroquinolones in the reproductive organs of adult male albino rats, and to see whether these changes are reversible after discontinuation of the drugs.Materials and Method:  Eighty adult male albino rats weighing 200 – 300 gms were randomly selected and divided into four groups i.e. A, B, C & D, having 20 animals in each group. A, B & C, were the experimental groups & D served as control group. All the groups were further divided into sub groups 1 & 2. Three fluoroquinolones i.e. Ciprofloxacin (135 mg / kg / day), Ofloxacin (75 mg / kg / day) & Enoxacin (12.5 mg / kg/ day) were given to the groups A, B & C respectively for 42 days. Animals of group D received dis-tilled water only. Animals of sub groups A1, B1, C1 &D1 were sacrificed on 42nd day and testicular tissue was obtained for morphological study. Animals of subgroups A2, B2, C2 & D2 were sacrificed on 84th day and testicular tissue for morphological changes was taken. No of leydig cells, height of epithelium and diameter of seminiferous tubules were taken as experimental parameters for morphological changes.Results:  The study indicated statistically significant (P < 0.05) decrease in height of epithelium, diameter of seminiferous tubules and no. of leydig cells in experimental groups as compared to the control groups.Conclusion:  The changes observed in morphology could lead to decrease in sperm count and testosterone levels. This study suggests gonadotoxic potentials of fluoroquinolones and adds concern to the indiscriminate and widespread use of fluoroquinolones and recommends more rational use of these drugs.


2020 ◽  
Vol 318 (6) ◽  
pp. C1092-C1106
Author(s):  
Wei Qu ◽  
Shuo Yuan ◽  
Chao Quan ◽  
Qian Huang ◽  
Qi Zhou ◽  
...  

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that is indispensable for the formation and maintenance of cilia and flagella; however, the implications and functions of IFT81 remain unknown. In this study, we disrupted IFT81 expression in male germ cells starting from the spermatocyte stage. As a result, homozygous mutant males were completely infertile and displayed abnormal sperm parameters. In addition to oligozoospermia, spermatozoa presented dysmorphic and nonfunctional flagella. Histological examination of testes from homozygous mutant mice revealed abnormal spermiogenesis associated with sloughing of germ cells and the presence of numerous multinucleated giant germ cells (symblasts) in the lumen of seminiferous tubules and epididymis. Moreover, only few elongated spermatids and spermatozoa were seen in analyzed cross sections. Transmission electron microscopy showed a complete disorganization of the axoneme and para-axonemal structures such as the mitochondrial sheath, fibrous sheath, and outer dense fibers. In addition, numerous vesicles that contain unassembled microtubules were observed within developing spermatids. Acrosome structure analysis showed normal appearance, thus excluding a crucial role of IFT81 in acrosome biogenesis. These observations showed that IFT81 is an important member of the IFT process during spermatogenesis and that its absence is associated with abnormal flagellum formation leading to male infertility. The expression levels of several IFT components in testes, including IFT20, IFT25, IFT27, IFT57, IFT74, and IFT88, but not IFT140, were significantly reduced in homozygous mutant mice. Overall, our study demonstrates that IFT81 plays an essential role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.


2021 ◽  
Vol 11 (1) ◽  
pp. 70-79
Author(s):  
Sassia O. Regeai ◽  
Salma A. Abusrer ◽  
Naema S. Shibani

Background: Male infertility has been on the rise since the past seven decades. Recently, in Libya, bee venom therapy (BVT) has become a popular method among alternative healthcare practitioners for treating male infertility. However, a literature search did not find any published studies that investigated the use of BVT for infertility treatment. Aim: To investigate the effect of bee venom on the male reproductive status through measurements of semen quality parameters and testicular histological changes in adult male mice. Methods: A total of 48 male mice were randomly divided into three experimental groups (which were subdivided into two subgroups with eight mice each) as follows: control, bee venom sting (BVS), and bee venom injection (BVI). The normal control subgroup mice were not subjected to any treatment, while the vehicle control subgroup mice were injected (i.p.) with 200 μl of 0.9% saline solution. In the BVS-treated subgroups, each mouse was stung by one live bee for five times (BVS-5) or seven times (BVS-7) every third day for 2 or 3 weeks. While each mouse in the BVI-treated subgroups received 23 μg/kg in a dose volume of 200 μl BVIs (i.p.) for five times (BVI-5) or seven times (BVI-7) every third day for 15 or 21 days. Results: The findings of this study showed that repeated bee venom treatment by sting or injection to adult male mice resulted in a significant decline in testosterone levels, sperm count, sperm motility, and a very significant increase in the percentage of abnormal sperm morphology; also, there were harmful testicular histological changes in the structural organization of seminiferous tubules and degenerative changes in the germinal epithelium compared to control group. Conclusion: The results of this study provide evidence for the low semen quality and adverse testicular histological changes in male mice treated with bee venom. Hence, there is a desperate need for educating alternative healthcare practitioners and infertile couples about the harmful effects of BVT on reproductive status.


2017 ◽  
Vol 40 (2) ◽  
pp. 336-347
Author(s):  
Nawal Rizkalla ◽  
Eman Habib ◽  
Mariam Amin ◽  
Diana Aziz

2017 ◽  
Vol 51 (4) ◽  
pp. 193-204 ◽  
Author(s):  
Dibyendu Dutta ◽  
In Park ◽  
Hiwot Guililat ◽  
Samuel Sang ◽  
Arpita Talapatra ◽  
...  

Abstract Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. Methods. Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone. The testosterone depletion effects after 7 days post-EDS were verified by replacing the testosterone exogenously into EDS-treated rats. Serum or testicular testosterone was measured by radioimmunoassay. Using qPCR, mRNAs of granzyme variants in testes were quantified. The germ cell apoptosis was identified by TUNEL assay and the localization of GZMK was by immunohistochemistry. Results. EDS treatment eliminated the Leydig cells and depleted serum and testicular testosterone. At 7 days post-EDS, testis weights were reduced 18% with increased germ cell apoptosis plus elevation GZMK expression. GZMK was not associated with TUNEL-positive cells, but was localized to stripped cytoplasm of spermatids. In addition, apoptotic round spermatids were observed in the caput epididymis. Conclusions. GZMK expression in testes is testosterone dependent. GZMK is located adjacent to germ cells in seminiferous tubules and the presence of apoptotic round spermatids in the epididymis suggest its role in the degradation of microtubules in ectoplasmic specializations. Thus, overexpression of GZMK may indirectly regulate germ cell apoptosis by premature release of round spermatids from seminiferous tubule lumen.


Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Yongmei Chen ◽  
Huizhen Wang ◽  
Nan Qi ◽  
Hui Wu ◽  
Weipeng Xiong ◽  
...  

Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM−/−) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM−/− testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM−/− mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM−/− Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM−/− mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.


2019 ◽  
Vol 9 (1) ◽  
pp. 13-16
Author(s):  
Twana Mustafa ◽  
Hamza Abdulah

Vascular disease and heart attacks are a common phenomenon in the modern world, where lipid accumulates inside blood vessels and causes plug, eventually heart stroke and death. Utilize lipidlowering drugs are the most effective factors to prevent heart disease. Atorvastatin is the most important drugs that used in this field. The aim of this study was to investigate the adverse effects of atorvastatin (20 mg/kg/b.wt/day) on some organs of albino. 12 adult male albino rats weighing 200 ± 20 g were used and divided into two groups: First group served as control group, was given 0.72 ml distilled water/rat. The second group was subjected to treatments with atorvastatin in a dose of 20 mg/kg/b.wt/day as a single daily dose (0.72 ml contained 1.44 mg of atorvastatin) orally by gastric tube for 4 weeks. Histological alterations were examined, and the results of atorvastatintreated groups showed changes in the kidney sections, which include focal tubular edema and glomerular atrophy, also liver sections revealed foci of lymphocyte accumulation, cytoplasmic vacuolization, as well as sections of the testes showed degenerative changes in the seminiferous tubules. According to this study, we can conclude that atorvastatin-induced various deleterious changes in the histological structure of the testes, kidneys and cause mild liver alteration of adult male albino rat.


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