Male infertility can be caused by chromosomal abnormalities, mutations, and epigenetic defects. Epigenetic modifiers pre-program hundreds of spermatogenic genes in spermatogonial stem cells (SSCs) for expression later in spermatids, but it remains mostly unclear whether and how those genes are involved in fertility. Here, we report that Wfdc15a, a WFDC family protease inhibitor pre-programmed by KMT2B, is essential for spermatogenesis. We found that Wfdc15a is a non-canonical bivalent gene carrying both H3K4me3 and facultative H3K9me3 in SSCs but is later activated along with the loss of H3K9me3 and acquisition of H3K27ac during meiosis. We show that Wfdc15a deficiency causes defective spermiogenesis at the beginning of spermatid elongation. Notably, depletion of Wfdc15a causes substantial disturbance of the testicular protease-antiprotease network and leads to an orchitis-like inflammatory response associated with TNFa expression in round spermatids. Together, our results reveal a unique epigenetic program regulating innate immunity crucial for fertility.
A non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis
Pathway to Independence Programme: our 2024 PI fellows
Following a successful pilot year in 2023 with a fantastic set of postdocs, we are delighted to announce our second cohort of Pathway to Independence (PI) fellows, who we will be supporting with training, mentoring and networking opportunities over the coming years.
Development presents…
Development is excited to host a webinar series showcasing the latest developmental biology and stem cell research. The webinars are chaired each month by a different Development Editor, who invites talks from authors of exciting new papers and preprints. Visit Development presents... on the Node to see which topics are coming up and to catch up on recordings of past webinars.
40 years of the homeobox
2024 marks the 40th year since the discovery of the homeobox in 1984, a landmark that fundamentally impacted several fields including genetics, developmental biology, neuroscience and evolution. To celebrate this anniversary, Development has commissioned a series of articles from leaders in the field demonstrating the impact of the homeobox discovery on different disciplines.
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
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