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  • Jensen, Christian Fuglesang SkjødtUniversity of Copenhagen,Gentofte Hospital (author)

Sertoli and Germ Cells Within Atrophic Seminiferous Tubules of Men With Non-Obstructive Azoospermia

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-06-02
  • Frontiers Media SA,2022

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:55ed861e-900a-47d5-bb87-2624b8312836
  • https://lup.lub.lu.se/record/55ed861e-900a-47d5-bb87-2624b8312836URI
  • https://doi.org/10.3389/fendo.2022.825904DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Background: Infertile men with non-obstructive azoospermia (NOA) have impaired spermatogenesis. Dilated and un-dilated atrophic seminiferous tubules are often present in the testes of these patients, with the highest likelihood of active spermatogenesis in the dilated tubules. Little is known about the un-dilated tubules, which in NOA patients constitute the majority. To advance therapeutic strategies for men with NOA who fail surgical sperm retrieval we aimed to characterize the spermatogonial stem cell microenvironment in atrophic un-dilated tubules. Methods: Testis biopsies approximately 3x3x3 mm3 were obtained from un-dilated areas from 34 patients. They were classified as hypospermatogenesis (HS) (n=5), maturation arrest (MA) (n=14), and Sertoli cell only (SCO) (n= 15). Testis samples from five fertile men were included as controls. Biopsies were used for histological analysis, RT-PCR analysis and immunofluorescence of germ and Sertoli cell markers. Results: Anti-Müllerian hormone mRNA and protein expression was increased in un-dilated tubules in all three NOA subtypes, compared to the control, showing an immature state of Sertoli cells (p<0.05). The GDNF mRNA expression was significantly increased in MA (P=0.0003). The BMP4 mRNA expression showed a significant increase in HS, MA, and SCO (P=0.02, P=0.0005, P=0.02, respectively). The thickness of the tubule wall was increased 2.2-fold in the SCO-NOA compared to the control (p<0.05). In germ cells, we found the DEAD-box helicase 4 (DDX4) and melanoma-associated antigen A4 (MAGE-A4) mRNA and protein expression reduced in NOA (MAGE-A: 46% decrease in HS, 53% decrease in MA, absent in SCO). In HS-NOA, the number of androgen receptor positive Sertoli cells was reduced 30% with a similar pattern in mRNA expression. The γH2AX expression was increased in SCO as compared to HS and MA. However, none of these differences reached statistical significance probably due to low number of samples. Conclusions: Sertoli cells were shown to be immature in un-dilated tubules of three NOA subtypes. The increased DNA damage in Sertoli cells and thicker tubule wall in SCO suggested a different mechanism for the absence of spermatogenesis from SCO to HS and MA. These results expand insight into the differences in un-dilated tubules from the different types of NOA patients.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Wang, DanyangCopenhagen University Hospital,University of Copenhagen (author)
  • Mamsen, Linn SaltoCopenhagen University Hospital (author)
  • Giwercman, AleksanderLund University,Lunds universitet,Reproduktionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Reproductive medicine, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-agi (author)
  • Jørgensen, NielsCopenhagen University Hospital (author)
  • Fode, MikkelGentofte Hospital,University of Copenhagen (author)
  • Ohl, DanaUniversity of Michigan (author)
  • Dong, LihuaCopenhagen University Hospital (author)
  • Hildorf, Simone EngmannOdense University Hospital (author)
  • Pors, Susanne ElisabethCopenhagen University Hospital (author)
  • Fedder, JensOdense University Hospital (author)
  • Ntemou, ElissavetCopenhagen University Hospital (author)
  • Andersen, Claus YdingCopenhagen University Hospital,University of Copenhagen (author)
  • Sønksen, JensUniversity of Copenhagen,Gentofte Hospital (author)
  • University of CopenhagenGentofte Hospital (creator_code:org_t)

Related titles

  • In:Frontiers in Endocrinology: Frontiers Media SA131664-2392

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