Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Epigenetics

Background:

• The PIWI-interacting RNA (piRNA) pathway is essential for transposon silencing in germline cells.
• HENMT1 (Hells domain-containing methyltransferase 1) and PIWI proteins are key components of this pathway.
• Understanding their role in human testis is crucial for reproductive health and cancer research.

Purpose of the Study:

• To define the expression patterns of HENMT1 and PIWI proteins in human testis.
• To investigate their association with transposon expression (LINE-1).
• To explore their correlation with infertility subtypes and testicular germ cell tumors (TGCTs).

Main Methods:

• Immunolocalization and RT-PCR on normal testis biopsies to determine HENMT1 and PIWIL1 localization.
• RT-qPCR analysis of 222 testis biopsies (normal, hypospermatogenesis, arrests, SCO, TGCTs) for HENMT1, PIWIL1-4, and LINE-1 expression.
• RT-qPCR analysis of HENMT1-overexpressing TCam2 cell lines.

Main Results:

• HENMT1 and PIWIL1 coexpressed in pachytene spermatocytes and spermatids.
• Expression of HENMT1, PIWIL1, and PIWIL2 correlated with germ cell content; low levels detected in some Sertoli cell-only (SCO) samples.
• Reduced expression of HENMT1, PIWIL1, and PIWIL2 observed in TGCTs.
• Expression of HENMT1, PIWIL2, and PIWIL4 associated with significantly lower transposon expression.
• HENMT1 overexpression in TCam2 cells reduced LINE-1 expression.

Conclusions:

• The transposon-regulating function of the piRNA pathway is conserved in adult human testis.
• HENMT1 and PIWI proteins exhibit germ-cell-specific expression.
• These proteins are essential for transposon control in the human testis.
• Dysregulation may be linked to infertility and TGCT development.