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Perspective: A Neuro-Hormonal Systems Approach to Understanding the Complexity of Cryptorchidism Susceptibility
Julia S Barthold1, Richard Ivell2
1Nemours Biomedical Research, Division of Urology, Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
Frontiers in Endocrinology
|August 8, 2018
Summary
Cryptorchidism, or undescended testes, involves genetic and environmental factors disrupting testicular descent. This study proposes a neuro-hormonal model implicating RBFOX genes and sensory signaling in cryptorchidism development.
Area of Science:
- Developmental Biology
- Genetics
- Endocrinology
Background:
- Nonsyndromic cryptorchidism is a common condition with risks of infertility and testicular cancer.
- Understanding its multifactorial causes is crucial for improved prediction and prevention.
Purpose of the Study:
- To synthesize clinical and translational data to understand the complexity of cryptorchidism.
- To propose an integrated neuro-hormonal model for testicular descent.
Main Methods:
- Comparative analysis of genome-wide association study (GWAS) data for cryptorchidism.
- Re-analysis of fetal testis transcriptome data from a rat model.
- Quantitative reverse transcription PCR (qRT-PCR) to assess sensory transcripts.
Main Results:
- RBFOX family genes identified as candidate susceptibility loci for cryptorchidism.
- Downregulation of Leydig cell progenitor genes observed in a rat model.
- Dysregulation of dorsal root ganglia (DRG) sensory transcripts found ipsilateral to undescended testes.
Conclusions:
- A multi-level, integrated neuro-hormonal model of testicular descent is proposed.
- Cryptorchidism susceptibility may result from combined genetic variants (e.g., RBFOX genes) and environmental exposures.
- A systems approach is essential for further insights into cryptorchidism causes and consequences.
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