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New discovery of cryptorchidism: Decreased retinoic acid in testicle
Jinpu Peng1, Lianju Shen1, Jinjun Chen1
1Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Key Laboratory of Pediatrics in Chongqing, Chongqing 400014, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.
Abstract:
This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group (n = 10) and normal control group (n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.
Insights
Flutamide-induced cryptorchidism in rats significantly reduces retinoic acid levels and impairs sperm production. This highlights potential therapeutic targets for treating infertility associated with undescended testes.
Area of Science:
- Reproductive Biology
- Toxicology
- Histopathology
Background:
- Cryptorchidism, or undescended testes, is a common cause of male infertility.
- Flutamide is an anti-androgen that can induce cryptorchidism in animal models.
- Retinoic acid plays a crucial role in spermatogenesis.
Purpose of the Study:
- To investigate the effects of flutamide-induced cryptorchidism on testicular histopathology and retinoic acid concentration.
- To explore potential new treatments for cryptorchidism-related infertility.
Main Methods:
- Induction of cryptorchidism in Sprague Dawley rats using flutamide.
- Histopathological examination using Hematoxylin and Eosin (HE) staining.
- Transmission electron microscopy (TEM) to assess Sertoli cell tight junctions.
- Sperm count and morphology analysis.
- Immunohistochemistry, Western blot, and quantitative Polymerase Chain Reaction (Q-PCR) for stimulated by retinoic acid gene 8 (Stra8) expression.
- High-performance liquid chromatography (HPLC) for retinoic acid quantification.
Main Results:
- Flutamide-induced cryptorchidism led to reduced sperm quantity and quality compared to controls.
- TEM revealed loosened tight junctions between Sertoli cells in the cryptorchidism group.
- Stra8 expression was significantly decreased in the cryptorchidism group.
- Retinoic acid levels were significantly lower in the testes of rats with flutamide-induced cryptorchidism.
Conclusions:
- Flutamide-induced cryptorchidism causes significant testicular damage, including disrupted Sertoli cell tight junctions and reduced Stra8 expression.
- Decreased retinoic acid content in testicular tissue is associated with spermatogenesis disorders in cryptorchidism.
- Targeting retinoic acid pathways may offer a novel therapeutic approach for infertility caused by cryptorchidism.
