Development of Apical-Out Human Fallopian Tube Organoids for Modeling Sperm-Epithelium Interactions

Area of Science:

• Reproductive biology
• Infertility research
• Organoid technology

Background:

• Elevated sperm DNA fragmentation index (DFI) is linked to adverse pregnancy outcomes, but mechanisms are unclear.
• The fallopian tube's role in sperm selection and its response to varying DFI levels are unknown.
• Lack of reliable in vitro models hinders investigation of sperm-fallopian tube interactions.

Purpose of the Study:

• To develop a reliable in vitro model for studying sperm-fallopian tube interactions.
• To investigate how the fallopian tube epithelium responds to sperm with different DFI levels.
• To elucidate mechanisms linking high DFI to infertility.

Main Methods:

• Established human fallopian tube organoids (FTOs) with reversed apical-out polarity.
• Utilized histological, immunofluorescence, ultrastructural, and gene expression analyses for validation.
• Developed a co-culture system for direct sperm-epithelium contact.

Main Results:

• Apical-out FTOs maintained epithelial integrity and supported sperm adhesion.
• FTOs improved sperm viability by reducing apoptosis and reactive oxygen species.
• Transcriptomic analysis showed normal sperm induced immune modulation, while high-DFI sperm triggered inflammatory responses.

Conclusions:

• Introduced and validated a novel apical-out human FTOs model for sperm-epithelium interaction studies.
• Demonstrated differential epithelial response to sperm DNA integrity.
• Provided new insights into the female reproductive tract's role in male factor infertility.