AZFc deletions do not affect the function of human spermatogonia in vitro

Area of Science:

• Reproductive Biology
• Human Genetics
• Cell Biology

Background:

• Azoospermic factor c (AZFc) deletions cause 10% of azoospermia or severe oligozoospermia.
• While AZFc deletions are understood molecularly, their impact on germ cell functionality remains unclear.
• Most men with AZFc deletions produce fertile sperm, implying differentiation can occur without the AZFc region.

Purpose of the Study:

• To investigate the functionality of spermatogonia in men with AZFc deletions.
• To compare in vitro behavior and gene expression of spermatogonia from AZFc-deleted individuals versus controls.

Main Methods:

• Cultured spermatogonia in vitro from six men with complete AZFc deletions and three normozoospermic controls.
• Assessed spermatogonia behavior through passages, germ cell cluster formation, and gene expression analysis.
• Analyzed expression of spermatogonial markers (UCHL1, ZBTB16, GFRA1) and differentiation markers (STAT3, SOHLH2, KIT, SYCP3).

Main Results:

• AZFc-deleted and control spermatogonia exhibited similar behavior during short-term (18 days) and long-term (48 days) in vitro culture.
• Expression levels of most tested spermatogonial and differentiation markers were comparable between groups.
• Melanoma antigen family A4 (MAGEA4) showed lower expression in AZFc-deleted samples during short-term culture.

Conclusions:

• Spermatogonia from men with AZFc deletions appear functionally similar to those from non-deleted men in vitro.
• This in vitro similarity suggests potential therapeutic strategies involving in vitro propagation and autotransplantation of spermatogonial stem cells (SSCs).
• Such strategies could enhance sperm counts and restore fertility in men with AZFc deletions.