Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

Caneguim, Breno Henrique; Cerri, Paulo Sérgio; Spolidório, Luís Carlos; Miraglia, Stefania; Sasso-Cerri, Estela

doi:10.1186/1477-7827-7-19

Cited by 41 publications

(41 citation statements)

References 45 publications

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“…This was confirmed in our experiment by the fact that the weights and tubular areas of denervated testes were lower on PD90 than on PD60. This abnormal development of seminiferous tubules is presumed to be the main cause of inhibiting spermatogenesis [23,24]. Thus, there were few mature spermatids in the seminiferous tubule lumen and a significant reduction in the cauda epididymal sperm count in the rats with denervated testes.…”

Section: Denervation On Testicular Developmentmentioning

confidence: 97%

“…The numbers of PCNA-positive cells and total cells (Sertoli cells, spermatogonia, spermatocytes and spermatids) per tubule were quantified in 10 tubules/animal [23]. Caspase-3-labeled cells were identified by brown nuclear, cytoplasmic and whole cell staining, as caspases translocate from the cytoplasm to the nucleus after activation [25].…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…The areas of the seminiferous epithelium and lumen were measured using Adobe Acrobat 7.0 Professional [23]. The following four categories classified according to the tubular area were used to evaluate the seminiferous tubules: a) reduced (19- [23,24].…”

Section: Morphometrymentioning

confidence: 99%

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Testicular Denervation in Prepuberty Rat Inhibits Seminiferous Tubule Development and Spermatogenesis

Huo

Zhang

et al. 2010

Journal of Reproduction and Development

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Abstract. In the adult rat, the superior spermatic nerve (SSN) and inferior spermatic nerve (ISN) are involved in regulating testosterone secretion and spermatogenesis, in addition to endocrine control mechanisms. However, there are currently few data on how the testis nerve supply regulates testicular development and related mechanisms. The present study was thus designed to investigate the regulating effects of testis nerve supply to testicular maturation, spermatogenesis and the involved mechanisms from prepuberty to adulthood in rats. We transected the SSNs and ISNs of rats on postnatal day (PD) 30 and then analyzed changes in testicular morphology and cauda epididymal sperm content, cell proliferation and apoptosis and primary spermatocyte meiosis on PD60 and PD90. The results demonstrated that testicular denervation significantly reduced testis mass, cauda epididymal sperm counts and serum testosterone concentrations. Proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 immunohistochemistry staining proved that the denervation had no influence on the proliferation of spermatogonia and primary spermatocytes, but obviously promoted the apoptosis of round spermatids and Leydig cells. It is novel that denervation reduced the meiotic activation of zygotene and pachytene spermatocytes through the expression of synaptonemal complex protein 3 (SCP3)-a marker of meiosis. In addition, RT-PCR showed that testis denervation significantly decreased testis 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) and luteinizing hormone receptor (LHR) mRNA levels, but had no obvious influence on testis follicle stimulating hormone receptor (FSHR) mRNA expression. These results suggest that the testicular nerve supply plays an important role in supporting seminiferous tubule development and spermatogenesis from prepuberty to adulthood. Key words: Apoptosis, Maldevelopment and spermatogenesis, Meiosis, Testicular denervation (J. Reprod. Dev. 56: [370][371][372][373][374][375][376][377][378] 2010) he development and function of the mammalian testis is regulated by endocrine factors and nervous supply. Compared with the endocrine effects, there are few studies on the nervous control of testicular development, although it has been reported that testicular denervation inhibits testosterone secretion and spermatogenesis in adult rats [1][2][3][4] and that spinal cord injury impairs the fertility of men [5].The nerve supply to the adult rat testis mainly involves the superior spermatic nerve (SSN) and inferior spermatic nerve (ISN). The SSN supplies the testis following the testicular artery [6,7], whereas the ISN enters the testis through the inferior testicular ligament [8]. Bilateral resection of the SSN blocks the acute stressinduced rise in plasma testosterone and decreases testicular luteinizing hormone receptor (LHR) expression [9][10][11]. Stimulation of the SSN increases both testosterone concentration and norepinephrine output in the spermatic vein [3], suggesting that the SSN has a positive effect on regulating testi...

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Section: Denervation On Testicular Developmentmentioning

confidence: 97%

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

See 1 more Smart Citation

Testicular Denervation in Prepuberty Rat Inhibits Seminiferous Tubule Development and Spermatogenesis

Huo

Zhang

et al. 2010

Journal of Reproduction and Development

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“…Currently, however, the side effects of tacrolimus regarding male fertility remains largely unknown [20] and reports indicating lower levels of inhibin B among men treated with tacrolimus compared with cyclosporine raises further questions [10]. Tacrolimus also induced morphological alterations in the seminiferous tubules and a reduction of the number of Sertoli cells in rats [24]. More studies are needed to evaluate the possible differences in aspects of fertility regarding modern immunosuppressive protocols and to study the mechanisms involved in Sertoli cell dysfunction among uremic and transplanted men.…”

Section: Discussionmentioning

confidence: 99%

Impact of Kidney Transplantation on Reproductive Hormone Levels in Males: A Longitudinal Study

Eckersten

Giwercman

Pihlsgård

et al. 2017

Nephron

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Background/Aims: Male patients with end-stage renal disease suffer from sexual disturbances and infertility. Disturbances in the hypothalamic-pituitary-gonadal axis are one of the causes of this. Decreased testosterone synthesis in Leydig cells of the testes and hyperprolactinemia are common. Kidney transplantation, unlike hemodialysis, normalizes these changes. However, how kidney transplantation affects Sertoli cell function is poorly understood. This study is aimed at investigating the changes in fertility-related hormones in men before, during, and after renal transplantation. Methods: This longitudinal and prospective single center study enrolled 12 men undergoing living donor kidney transplantation. Plasma levels of creatinine, cystatin C, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, sex hormone-binding globulin, inhibin B, and anti-Müllerian hormone (AMH) were assayed at 10 different time points before, during, and after kidney transplantation. Results: A rapid decrease in creatinine and cystatin C levels indicated successful renal transplantation. High pre-transplantation plasma levels of prolactin (mean 516 ± 306 mIE/L) and LH (9.4 ± 4.7 IU/L) were normalized after 7 days (248 ± 161 mIE/L and 6.1 ± 3.1 IU/L, respectively). Testosterone decreased rapidly during transplantation and increased again one week post-transplantation. Sertoli cell-derived hormone inhibin B decreased after transplantation, and there was a small non-significant trend of increased AMH after 12 months. Conclusion: Sertoli cell function, based on AMH and inhibin B levels, does not improve to the same extent or as fast as Leydig cell function after kidney transplantation, as determined by testosterone and LH levels.

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“…In addition to germ cells, a significant decrease in the number of SCs was also observed. These epithelial disorders seem to be related to a possible effect of tacrolimus on the peritubular tissue due to the fact that portions of this tissue surrounding the damaged seminiferous tubules were folded in tacrolimus-treated rats [Caneguim et al, 2009].…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

Caneguim

Cerri

Spolidório

et al. 2011

Cells Tissues Organs

Self Cite

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Treatment with tacrolimus (FK-506) has been shown to induce a significant decrease in the number of spermatocytes, spermatids, and Sertoli cells. Regarding the importance of the peritubular tissue for the maintenance of Sertoli cells, the integrity of the cellular and extracellular components of the peritubular tissue was evaluated in adult rats that were treated with 1 mg/kg/day of FK-506 for 30 and 60 days. Testicular sections were used for a quantitative analysis of the peritubular cells (PCs) and were submitted to the PAS method. Paraffin sections were submitted to the TUNEL method and to immunohistochemistry for the detection of caspase-3. Several testicular fragments were analyzed under a transmission electron microscope (TEM). A weak PAS reaction was noted in the peritubular tissue of the tacrolimus-treated animals. Next to the damaged peritubular tissue, the Sertoli cell nuclei were absent or dislocated from the basement membrane. In the treated animals, the number of PCs decreased significantly compared to the control animals, and these cells showed apoptotic features, were TUNEL positive, and were caspase-3 immunolabeled. Using the TEM, apoptosis was confirmed in myoid cells; moreover, the thickness and undulation of the basal laminae and an enlargement of the collagen I layer adjacent to the myoid cells was observed. Long-term treatment with the immunosuppressor induced peritubular myoid cell death by apoptosis and disarrangement of the peritubular extracellular layers. Future studies are necessary to confirm whether the structural alterations in the seminiferous epithelium are related to the effect of FK-506 on peritubular tissue.

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Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

Cited by 41 publications

References 45 publications

Testicular Denervation in Prepuberty Rat Inhibits Seminiferous Tubule Development and Spermatogenesis

Testicular Denervation in Prepuberty Rat Inhibits Seminiferous Tubule Development and Spermatogenesis

Impact of Kidney Transplantation on Reproductive Hormone Levels in Males: A Longitudinal Study

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

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