An intrascrotal bioadhesive nanoplatform for sustained hydrogen delivery ameliorates age-associated testicular dysfunction.
- 1Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China.
- 2Allergy and Cancer Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.
Abstract
Testicular aging is characterized by progressive spermatogenic decline. Accumulating oxidative injury and insufficient metabolic support from Sertoli cells may contribute to this process. Although molecular hydrogen has shown antioxidant potential, its therapeutic application in reproductive aging is limited by rapid dissipation after administration. To overcome this barrier, we developed the localized hydrogen-releasing system S-H/B. This platform integrates hydrogenated silicon nanosheets (S-H) with a bioadhesive polymer, aldehyde-functionalized polylactic acid-hyperbranched polyglycerol (PLA-HPG-al). The resulting formulation adhered to peritesticular tissue following intrascrotal injection, showed prolonged local retention, and enabled sustained hydrogen release under physiological conditions. This sustained local hydrogen delivery reduced age-associated testicular degeneration and promoted spermatogenesis in aged mice. Notably, single-cell RNA sequencing revealed enhanced HIF-1 signaling and glycolysis-related transcriptional programs in aged Sertoli cells following S-H/B treatment. Further mechanistic analyses indicated that S-H/B reduced ONOO⁻ levels and limited PHD1-dependent HIF-1α hydroxylation, thereby slowing HIF-1α degradation and promoting its nuclear localization. Consistently, S-H/B increased glycolytic enzyme expression, glucose uptake, glycolytic flux, and lactate production in Sertoli cells, whereas HIF-1α inhibition attenuated these metabolic changes. The increased lactate production may have contributed to improved seminiferous epithelial function. Overall, this work presents a bioadhesive hydrogen delivery strategy for age-associated male reproductive dysfunction and suggests that metabolic remodeling in Sertoli cells may contribute to its beneficial effects.
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BibTeX
@article{liang2026intrascrotal,
title = {{An intrascrotal bioadhesive nanoplatform for sustained hydrogen delivery ameliorates age-associated testicular dysfunction.}},
author = {Shu Liang and Jiawei Lv and Zun Li and Zheng Li and Jiachun Jiang and Shaoqing Yu and Cheng Wang and Xiongjun Wang and Lingyun Xiao and Guanzhen Yu},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103732},
url = {https://europepmc.org/article/MED/42898181},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - An intrascrotal bioadhesive nanoplatform for sustained hydrogen delivery ameliorates age-associated testicular dysfunction.
AU - Shu Liang
AU - Jiawei Lv
AU - Zun Li
AU - Zheng Li
AU - Jiachun Jiang
AU - Shaoqing Yu
AU - Cheng Wang
AU - Xiongjun Wang
AU - Lingyun Xiao
AU - Guanzhen Yu
PY - 2026
DA - 2026/10/07
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103732
UR - https://europepmc.org/article/MED/42898181
AB - Testicular aging is characterized by progressive spermatogenic decline. Accumulating oxidative injury and insufficient metabolic support from Sertoli cells may contribute to this process. Although molecular hydrogen has shown antioxidant potential, its therapeutic application in reproductive aging is limited by rapid dissipation after administration. To overcome this barrier, we developed the localized hydrogen-releasing system S-H/B. This platform integrates hydrogenated silicon nanosheets (S-H) with a bioadhesive polymer, aldehyde-functionalized polylactic acid-hyperbranched polyglycerol (PLA-HPG-al). The resulting formulation adhered to peritesticular tissue following intrascrotal injection, showed prolonged local retention, and enabled sustained hydrogen release under physiological conditions. This sustained local hydrogen delivery reduced age-associated testicular degeneration and promoted spermatogenesis in aged mice. Notably, single-cell RNA sequencing revealed enhanced HIF-1 signaling and glycolysis-related transcriptional programs in aged Sertoli cells following S-H/B treatment. Further mechanistic analyses indicated that S-H/B reduced ONOO⁻ levels and limited PHD1-dependent HIF-1α hydroxylation, thereby slowing HIF-1α degradation and promoting its nuclear localization. Consistently, S-H/B increased glycolytic enzyme expression, glucose uptake, glycolytic flux, and lactate production in Sertoli cells, whereas HIF-1α inhibition attenuated these metabolic changes. The increased lactate production may have contributed to improved seminiferous epithelial function. Overall, this work presents a bioadhesive hydrogen delivery strategy for age-associated male reproductive dysfunction and suggests that metabolic remodeling in Sertoli cells may contribute to its beneficial effects.
SN - 2590-0064
ER -