<em>Zingiber mioga</em> Alters Testicular Immune Microenvironment and Spermatogenesis by Decreasing Androgen Synthesis in Mice

Androgen from the testis is critical for maintaining immune environmental homeostasis and male spermatogenesis. Zingiber mioga (Z. mioga) is an edible vegetable belonging to the ginger family that has shown antimicrobial activity. Previous research has reported that the ginger species showed potential treatment effects in androgen-driven disease to enhance the immune system by inhibiting androgen synthesis and function. However, the anti-androgen effect of the ginger family and subsequently reproductive outcome has not been evaluated. In this study, the testis development and sperm generation were evaluated in control and feeding Z. mioga mice. The global gene expression pattern was examined in testis by RNA-sequencing and qRT-PCR. The results showed that testis/body weight significantly decreased from 32.5%±0.01 to 25%±0.01 and sperm concentration reduced from 7.6*106/ml±0.6 to 4.9*106/ml±0.6 after feeding Z. mioga. RNA-Seq data revealed that 480 transcripts were differentially expressed between control and treatment groups, with 300 upregulated genes and 180 downregulated genes in the treatment group compared with the control. Further analysis revealed that differential transcripts were associated with androgen synthesis and immunity function, including downregulated Scd1, Star, Cyp11a1, Hsd3b6, Cyp17a1, Hsd17b3, Lhcgr and upregulated MHC II+ marker genes. The results of gene expression difference were confirmed by qRT-PCR. This study demonstrated the important effects of Z. mioga intake on the process of spermatogenesis and revealed the potential anti-androgen action mechanism of ginger species regulating androgen synthesis and improving immunity homeostasis.