Exosome Nanotherapy Rescues Male Fertility by Delivering Integrin β1 to Repair Environmental Stress-Damaged Testes

Area of Science:

• Reproductive biology
• Nanomedicine
• Cellular biology

Background:

• Environmental thermal-mechanical (T&M) stress poses a global threat to male fertility.
• Currently, no molecular therapies exist for stress-induced testicular damage.

Purpose of the Study:

• To investigate macrophage-derived exosomes (Mφ-EVs) as a nanomedicine for T&M stress-induced male infertility.
• To determine the therapeutic efficacy of Mφ-EVs delivering Integrin β1 (ITGB1) for restoring fertility.

Main Methods:

• Utilized validated T&M stress models in C57BL/6 mice and GC-2 spermatocytes.
• Administered Mφ-EVs and assessed sperm motility, abnormalities, and cytoskeletal protein expression.
• Employed biodistribution tracking, molecular docking, and cellular thermal shift assays.

Main Results:

• T&M stress caused significant reproductive dysfunction, including reduced sperm motility and increased abnormalities.
• Mφ-EVs treatment normalized sperm parameters and cytoskeletal homeostasis.
• Exosomal ITGB1 was shown to form high-affinity complexes with ITGA1, stabilizing protein structure.

Conclusions:

• Macrophage-derived exosomes (Mφ-EVs) represent a novel, clinically translatable nanotherapy for male infertility.
• This exosome-based approach effectively repairs T&M stress-induced testicular damage by delivering ITGB1.
• Scalable nanotherapy holds potential for addressing widespread fertility disorders caused by environmental factors.