Immunohistology of aquaporin-1 and stem cell factor-receptor in human undescended testes

Nicòtina, Piero Antonio; Romeo, Carmelo; Arena, Salvatore; Impellizzeri, Pietro; Antonuccio, Pietro; Arena, Francesco; Zuccarello, Biagio; Giuseppe, Romeo

doi:10.1007/s00383-003-1125-z

Cited by 12 publications

(5 citation statements)

References 14 publications

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“…, 2006). As c‐kit is reported to be expressed in prepubertal human testis (Nicotina et al. , 2004), and the pattern of expression of the PDGF receptor in fetal and adult human testicular tissue is suggested to be comparable with that in rats (Basciani et al.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of tyrosine kinases PDGFR and C‐Kit by imatinib mesylate interferes with postnatal testicular development in the rat

Nurmio¹,

Toppari

Zaman

et al. 2007

Int J of Andrology

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The tyrosine kinase receptor c-kit and its interaction with the ligand, stem cell factor (SCF), play an essential role in the developing testis. C-kit is important for the development of the Leydig cells and for the migration, proliferation and survival of spermatogonia. Platelet-derived growth factor (PDGF) and its tyrosine kinase receptor (PDGFR) are important for the development of Leydig cells and myoid cells. The chemotherapeutic agent, imatinib mesylate (STI571, Glivec; Novartis) inhibits both of these tyrosine kinase receptors. Three-day treatment of immature male rats (SD) with imatinib (150 mg/kg) on postnatal days 5-7 delayed the formation of germ-line stem cell pool, reduced proliferation of type A spermatogonia and induced germ cell apoptosis. PDGFR-mediated proliferation of mesenchymal myoid precursors was also decreased and the length of the seminiferous cord was reduced. However, at the age of 11 weeks the exposed animals had normal epididymal sperm counts, whereas plasma levels of luteinizing hormone and follicle stimulating hormone were significantly increased. Imatinib serves as a good tool to study postnatal formation of the male germ-line stem cell pool and factors determining the final testicular size. As development of the human testis is controlled by the same mechanisms, further studies with primate and human models are needed to explore whether imatinib affects the testis in children as well.

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Section: Discussionmentioning

confidence: 99%

Inhibition of tyrosine kinases PDGFR and C‐Kit by imatinib mesylate interferes with postnatal testicular development in the rat

Nurmio¹,

Toppari

Zaman

et al. 2007

Int J of Andrology

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Section: Discussionmentioning

confidence: 99%

“…In this study, clear signals of mRNA expression were detected in the human testis but neither the RNA nor the protein was detected in ejaculated spermatozoa. Expression of AQP1 in the normal human testis is restricted to the endothelial cells of blood vessels in normal tissue (Nicotina et al, 2004). Despite positive Western results in canine spermatozoa, where antibody specificity and protein localization still need to be demonstrated (Ito et al, 2008), the absence of AQP1 protein from murine (Lu et al, 2008) and ovine spermatozoa (Curry et al, 1995b) has been reported.…”

Section: Discussionmentioning

confidence: 99%

Aquaporins in the human testis and spermatozoa – identification, involvement in sperm volume regulation and clinical relevance

Yeung¹,

Callies²,

Tüttelmann

et al. 2010

Int J of Andrology

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Despite the high water-permeability of human spermatozoa, little is known about the identity and the role of aquaporins (AQP) in them or germ cells. Using ejaculates from donors, sperm AQPs were identified by western blotting followed by the analysis of mRNA with RT-PCR. Protein expression in the testis and spermatozoa was localized by immunocytochemistry. Inhibitors were used to investigate the involvement of aquaporins in water transport when ejaculated spermatozoa were swollen in medium mimicking uterine hypo-osmolality by quinine that blocks volume regulation. Sperm AQP7 and AQP8 in 39 infertile patients and 11 healthy donors were quantified by flow cytometry. AQP1 was absent from spermatozoa. Sperm and testicular AQP7-9 had nucleotide sequences identical to those of somatic cells but AQP8 mRNA also showed shorter variants. AQP7 was expressed abundantly by round and elongated spermatids and ejaculated spermatozoa, AQP8 by all germ cells and spermatozoa, and AQP9 rarely by spermatocytes or Sertoli cells. Protein bands showed specificity by western blotting for AQP7 and AQP8 but not AQP9. The absence of sperm AQP9 was further suggested by the ineffectiveness of its inhibitor phloretin in blocking quinine-induced swelling, but HgCl(2,) which inhibits AQP8, was effective. Sperm AQP7 expression was correlated with progressive motility and was lower in patients than in donors. Sperm AQP8 expression was inversely correlated with the extent of sperm coiling, which is a swelling phenomenon, but showed no difference between patients and donors. In conclusion, AQP7 and AQP8 were identified in human spermatozoa and could play a role in glycerol metabolism and water transport respectively.

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“…However, similar observations were noticed in that study of Nurmio regarding the number of Sertoli cells as the number of Sertoli cells /cord cross section increased at PND70 as in our study as Sertoli cells do not show an expressing of c-kit or PDGFR receptors, so, Sertoli cells undergo proliferation as in normal states (35). Although the present study used the rat as an animal model, immature human testes is also susceptible to the impact of imatinib since c-kit is reported to show an expression in human testis at prepuberty (39) and the mode of expression of the PDGF receptor in human fetus and adult testicular section is similar to that in rats (31).…”

Section: Discussionmentioning

confidence: 99%

A histological study on the effect of imatinib on the rats' testis after early postnatal exposure

Khalel¹,

Al-Ashoo²

2021

IJVS

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The safety region of imatinib, and markedly its role in testicular toxicity has been studied in a controversial manner in current years. This study was designed to address the repercussion of administration of groups of pups with imatinib mesylate (at neonatal or infantile periods) using histological analysis of their testes in several end points and in adulthood. Intact pups (albino-male) exposed to 200 mg/kg of oral imatinib once daily at neonatal and early infantile period on PND 1 to PND10 (for ten days). All experiments performed with age and weight matched control which administered with Distilled water. Pups were into categorized into 4 subgroups, according to the ages of euthanasia: 15 days postpartum (PND); 40days postpartum; 70 days postpartum and 140 days postpartum. The histological analysis was conducted in blind fashion after staining with (Harris Hematoxylin and Eosin stain. Ten randomly selected testicular sections from each rat were analyzed qualitatively and quantitavely. In addition, Johnsen' scores were used to analyze the effect of drug on spermatogenesis. Data were recorded and value is considered as significant when it P<0.05. imatinib induced several alterations in testicular sections in comparison with those of control group including significant reduction of number of peripheral germ cells layers at PND 15. Different histological changes were more frequent in tissues obtained from rats euthanized at PND 40 and PND70. Quantitative changes were also noticed as diminishing of seminiferous tubular diameter of the, height of epithelial layer especially at PND70. Partial recovery was noticed in sections of rats euthanized at PND140. In conclusion, imatinib does affect the histology of rat testis markedly, but this effect is reversible once the drug administration is ceased. That may provide a benefit for the specialists in planning and addressing of the fertility associated issues in young patientsthroughout their reproductive periods-who are being on imatinib treatment for gastrointestinal tumors and chronic myeloid leukemia (CML).

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Immunohistology of aquaporin-1 and stem cell factor-receptor in human undescended testes

Cited by 12 publications

References 14 publications

Inhibition of tyrosine kinases PDGFR and C‐Kit by imatinib mesylate interferes with postnatal testicular development in the rat

Inhibition of tyrosine kinases PDGFR and C‐Kit by imatinib mesylate interferes with postnatal testicular development in the rat

Aquaporins in the human testis and spermatozoa – identification, involvement in sperm volume regulation and clinical relevance

A histological study on the effect of imatinib on the rats' testis after early postnatal exposure

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