Xie, F.-Y. | Search bioRxiv

bioRxiv2025

Integrative analysis of GTEx data reveals that systemic transcriptomes correlate with human spermatogenic dysfunction

Declining of male fertility may stem from intrinsic testicular dysfunction or systemic influences from other tissues. However, beyond the hypothalamic-pituitary-testis axis, little is known about which organs interact with the testes or whether they affect spermatogenic capacity. To investigate this, we analyzed GTEx open-access data, comparing transcriptomic profiles across various tissues in men with high and low testicular spermatogenic activity. Our findings reveal significant associations between testicular function and the pituitary gland, adrenal gland, lungs, liver, and key brain regions involved in neuroendocrine regulation, including the amygdala, substantia nigra, anterior cingulate cortex, and frontal cortex. These results suggest potential extragonadal pathways that modulate male fertility, highlighting candidate biomarkers for testicular dysfunction and novel therapeutic targets for infertility intervention.

developmental biology↗

bioRxiv2020

Double-strand breaks can induce DNA replication and damage amplification in G2 phase-like oocytes of mice

Break-induced DNA replication (BIR) have been detected not only in the genome of rare disease patients but also in cancer cells, however, the mechanisms of BIR formation havent been explained in details. In the late G2 phase-like mouse oocytes, we found DNA double-strand breaks (DSBs) could induce Rad51 dependent small-scale DNA replication. In addition, we also found the DSBs could be amplified in mouse oocytes, and the amplification could be inhibited by Rad51 inhibitor IBR2 and DNA replication inhibitor ddATP. Lastly, we found the DSB repair was relatively inefficiency in hybrid mouse oocytes compared with that of the purebred mouse oocytes. We found DSBs could induce BIR more easier in hybrid mouse oocytes, indicating the DNA repair in oocytes could be affected by the sequence differences between homologous chromatids. In summary, our results indicated that the condensed chromatin configuration in late G2 phase and the sequence similarity between broken DNA and template DNA are causing factors of BIR in mammalian genome, and the DNA damage could be amplified in late G2 phase cells.

genetics↗