X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome

Sofia B. Winge; Niels E Skakkebæk; Lise Aksglaede; Gülizar Saritas; Ewa Rajpert-De Meyts; Anders Juul; Ellen Goossens; Kristian Almstrup

doi:10.1038/s41419-024-06792-6

X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome

Sofia B. Winge, Niels E Skakkebæk, Lise Aksglaede, Gülizar Saritas, Ewa Rajpert-De Meyts, Anders Juul, Ellen Goossens, Kristian Almstrup

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.

Original language	English
Article number	396
Number of pages	9
Journal	Cell & Death Disease
Volume	15
DOIs	https://doi.org/10.1038/s41419-024-06792-6
Publication status	Published - 5 Jun 2024

Bibliographical note

Funding Information:
We thank the Novo Nordisk Foundation (grant no. NNF21OC0069913 to KA) for financial support. The authors have benefited from networking grants of COST Action CA20119 (ANDRONET) supported by European Cooperation in Science and Technology (www.cost.eu). The authors wish to acknowledge Lisa Leth Maroun and Svetlana Teplaia for assistance with the DNA FISH staining, and John E. Nielsen and Ana Ricci C. G. Nielsen for technical assistance with the IHC experiments. We also want to thank Professor Mikkel H. Schierup for helpful input to the manuscript.

Publisher Copyright:
© The Author(s) 2024.

Keywords

klinefelter syndrome
X chromosome loss
Sertoli cells
Spermatogenesis

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10.1038/s41419-024-06792-6Licence: CC BY

Cite this

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title = "X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome",

abstract = "Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.",

keywords = "klinefelter syndrome, X chromosome loss, Sertoli cells, Spermatogenesis",

author = "Winge, {Sofia B.} and Skakkeb{\ae}k, {Niels E} and Lise Aksglaede and G{\"u}lizar Saritas and {Rajpert-De Meyts}, Ewa and Anders Juul and Ellen Goossens and Kristian Almstrup",

note = "Funding Information: We thank the Novo Nordisk Foundation (grant no. NNF21OC0069913 to KA) for financial support. The authors have benefited from networking grants of COST Action CA20119 (ANDRONET) supported by European Cooperation in Science and Technology (www.cost.eu). The authors wish to acknowledge Lisa Leth Maroun and Svetlana Teplaia for assistance with the DNA FISH staining, and John E. Nielsen and Ana Ricci C. G. Nielsen for technical assistance with the IHC experiments. We also want to thank Professor Mikkel H. Schierup for helpful input to the manuscript. Publisher Copyright: {\textcopyright} The Author(s) 2024.",

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doi = "10.1038/s41419-024-06792-6",

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AU - Winge, Sofia B.

AU - Skakkebæk, Niels E

AU - Aksglaede, Lise

AU - Saritas, Gülizar

AU - Rajpert-De Meyts, Ewa

AU - Juul, Anders

AU - Goossens, Ellen

AU - Almstrup, Kristian

N1 - Funding Information: We thank the Novo Nordisk Foundation (grant no. NNF21OC0069913 to KA) for financial support. The authors have benefited from networking grants of COST Action CA20119 (ANDRONET) supported by European Cooperation in Science and Technology (www.cost.eu). The authors wish to acknowledge Lisa Leth Maroun and Svetlana Teplaia for assistance with the DNA FISH staining, and John E. Nielsen and Ana Ricci C. G. Nielsen for technical assistance with the IHC experiments. We also want to thank Professor Mikkel H. Schierup for helpful input to the manuscript. Publisher Copyright: © The Author(s) 2024.

PY - 2024/6/5

Y1 - 2024/6/5

N2 - Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.

AB - Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.

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KW - Spermatogenesis

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X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome

Abstract

Bibliographical note

Keywords

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Other files and links

SRP89: SRP-Groeifinanciering: The spermatogonial stem cell: the key to prevention and treatment of male infertility

Cite this

X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Projects

SRP89: SRP-Groeifinanciering: The spermatogonial stem cell: the key to prevention and treatment of male infertility

Cite this