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Published on: December 8, 2021
Testicular expression of long non-coding RNAs is affected by curative GnRHa treatment of cryptorchidism
Faruk Hadziselimovic1, Gilvydas Verkauskas2, Beata Vincel3
1Cryptorchidism Research Institute, Children's Day Care Center, 4410 Liestal, Switzerland.
Background:
Cryptorchidism is a frequent endocrinopathy in boys that has been associated with an increased risk of developing testicular cancer and infertility. The condition is curable by combined surgery and hormonal treatment during early pre-pubertal stages using gonadotropin releasing hormone agonist (GnRHa). However, whether the treatment also alters the expression of testicular long non-coding RNAs (lncRNAs) is unknown. To gain insight into the effect of GnRHa on testicular lncRNA levels, we re-analyzed an expression dataset generated from testicular biopsies obtained during orchidopexy for bilateral cryptorchidism.
Results:
We identified EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, and MTOR-AS1 as potentially relevant for the stimulation of cell proliferation mediated by GnRHa based on their direct or indirect association with rapidly dividing cells in normal and pathological tissues. Surgery alone failed to alter the expression of these transcripts.
Conclusion:
Given that lncRNAs can cooperate with chromatin-modifying enzymes to promote epigenetic regulation of genes, GnRHa treatment may act as a surrogate for mini-puberty by triggering the differentiation of Ad spermatogonia via lncRNA-mediated epigenetic effects. Our work provides additional molecular evidence that infertility and azoospermia in cryptorchidism, resulting from defective mini-puberty cannot be cured with successful orchidopexy alone.
Insights
Gonadotropin releasing hormone agonist (GnRHa) treatment, not surgery alone, alters testicular long non-coding RNA (lncRNA) expression in boys with cryptorchidism. This suggests GnRHa may improve fertility outcomes by influencing epigenetic regulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Cryptorchidism is a common endocrine disorder in boys, linked to higher risks of testicular cancer and infertility.
- Current treatment involves surgery and hormonal therapy with gonadotropin releasing hormone agonist (GnRHa) during pre-puberty.
- The impact of GnRHa on testicular long non-coding RNA (lncRNA) expression remains largely unknown.
Purpose of the Study:
- To investigate the effect of GnRHa treatment on testicular lncRNA expression in boys with cryptorchidism.
- To identify specific lncRNAs potentially involved in GnRHa-mediated cellular processes.
Main Methods:
- Re-analysis of a gene expression dataset from testicular biopsies of boys undergoing orchidopexy for bilateral cryptorchidism.
- Identification of lncRNAs associated with cell proliferation and GnRHa treatment effects.
Main Results:
- Surgery alone did not affect the expression of the studied lncRNAs.
- Several lncRNAs, including EGFR-AS1, Linc-ROR, and MTOR-AS1, were identified as potentially relevant to GnRHa-stimulated cell proliferation.
- These identified lncRNAs showed association with rapidly dividing cells in various tissues.
Conclusions:
- GnRHa treatment may influence Ad spermatogonia differentiation through lncRNA-mediated epigenetic mechanisms, potentially mimicking natural mini-puberty.
- Successful orchidopexy alone may not resolve infertility or azoospermia associated with cryptorchidism due to defective mini-puberty.
- lncRNAs play a role in the epigenetic regulation of genes, offering a molecular basis for GnRHa's therapeutic effects.
