Mice 3D testicular organoid system as a novel tool to study Zika virus pathogenesis
Wei Yang1, Chen Zhang2, Yan-Hua Wu2
1Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China; Department of Neurosurgery, Capital Medical University Sanbo Brain Hospital, Beijing, 100093, China.
Abstract:
Zika virus (ZIKV) poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage. However, deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury. Organoids are relatively simple in vitro models, which could mimic the pathological changes of corresponding organs. In this study, we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice. Similar to the testis, this organoid system has a blood-testis barrier (BTB)-like structure and could synthesize testosterone. ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis. Therefore, our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.
Insights
Researchers developed a 3D testicular organoid model to study Zika virus (ZIKV) effects on male reproductive health. This model mimics the human testis, aiding research into ZIKV-induced testicular injury.
Area of Science:
- Reproductive Biology
- Virology
- Biomedical Engineering
Background:
- Zika virus (ZIKV) is a global health concern linked to neurological and male reproductive damage.
- Limited human testicular samples impede research on ZIKV's impact on the male reproductive system.
- Organoid technology offers a promising in vitro approach to model organ-specific pathologies.
Purpose of the Study:
- To develop a 3D testicular organoid model for studying ZIKV-induced male reproductive injury.
- To assess the model's fidelity in mimicking mammalian testicular structure and function.
- To evaluate ZIKV tropism and pathological effects within the developed testicular organoids.
Main Methods:
- Construction of a 3D testicular organoid using primary testicular cells from adult BALB/c mice.
- Characterization of the organoid's blood-testis barrier (BTB)-like structure and testosterone synthesis.
- Infection of the organoid model with ZIKV to observe tropism and pathological changes.
Main Results:
- The 3D testicular organoid successfully replicated key features of the native testis, including a BTB-like structure and testosterone production.
- ZIKV exhibited similar tropism in the organoid model as observed in mammalian testes.
- Pathological changes induced by ZIKV in the organoid mirrored those seen in vivo.
Conclusions:
- The developed 3D testicular organoid serves as a viable and reproducible in vitro model for investigating ZIKV-induced testicular injury.
- This model overcomes limitations posed by the scarcity of human testicular samples.
- It provides a valuable platform for understanding ZIKV's reproductive health implications and for developing potential therapeutic strategies.
