Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing
Ben Bar-Sadeh; Or E. Amichai; Lilach Pnueli; Khurshida Begum; Gregory Leeman; Richard D. Emes; Reinhard Stöger; Gillian R. Bentley
BMC Biology2022
Summary (paraphrased)
Women who experienced high energetic demands in childhood show altered adult ovarian function and shorter reproductive lifespan, suggesting early-life programming of reproduction. Combining a mouse model with methylation analysis of proxy-tissue DNA from a well-characterized cohort of Bangladeshi migrants in the UK, the authors trace this programming to epigenetic regulation of 5-alpha-reductase-1. Methylation changes at the SRD5A1 locus are linked to later pubertal onset and altered reproductive function, showing that the gene encoding a key neurosteroidogenic enzyme is itself subject to lasting epigenetic control. The study demonstrates adaptive plasticity of 5-AR expression through DNA methylation in both animal and human data.
Why it’s in the corpus
Proof of principle that 5-alpha-reductase expression is epigenetically tunable with lasting phenotypic consequences — a direct precedent for the epigenetic persistence hypothesis in post-drug syndromes.
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SRD5A1SRD5A2SRD5A3PFS-0112025Core corpus - Powers gene claim
SRD5A1 — epigenetic silencing (acquired, not germline)
Confidence: direct
SRD5A1 (like AKR1C enzymes) can be epigenetically silenced, and valproic acid (an HDAC inhibitor) appears able to reverse this in his patients, with slow normalization over months.
SRD5A1PGL-SRD5A1circa May 2026PFSCore corpus