ArticleEndocrinology2022
Human INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice.
Article in Endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- A Western-style diet exacerbates male infertility in M1ap knockout mice.Human reproduction (Oxford, England) · 2026Article
- CCDC89 is required for optimal sperm motility and male fertility in mammals.Human reproduction (Oxford, England) · 2025Article
- Introduction to androgenetics: terminology, approaches, and impactful studies across 60 years.Andrology · 2025Review
- Improvement in Heat Stress-Induced Damage to Sperm Quality Following Fecal Microbiota Transplantation from L-Arginine-Treated Mice.Animals : an open access journal from MDPI · 2025Article
- AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.Cell death & disease · 2024Article
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Authors and funding
16 authors at 7 institutions in 6 countries.
Funding
Abstract
Testicular-derived inhibin B (α/β B dimers) acts in an endocrine manner to suppress pituitary production of follicle-stimulating hormone (FSH), by blocking the actions of activins (β A/B/β A/B dimers). Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising from uniparental disomy of chromosome 2 in the INHBB gene (β B-subunit of inhibin B and activin B) in a man suffering from infertility (azoospermia). In this study, we aimed to test the causality of the p.Met360Thr variant in INHBB and testis function. Here, we used CRISPR/Cas9 technology to generate InhbbM364T/M364T mice, where mouse INHBB p.Met364 corresponds with human p.Met360. Surprisingly, we found that the testes of male InhbbM364T/M364T mutant mice were significantly larger compared with those of aged-matched wildtype littermates at 12 and 24 weeks of age. This was attributed to a significant increase in Sertoli cell and round spermatid number and, consequently, seminiferous tubule area in InhbbM364T/M364T males compared to wildtype males. Despite this testis phenotype, male InhbbM364T/M364T mutant mice retained normal fertility. Serum hormone analyses, however, indicated that the InhbbM364T variant resulted in reduced circulating levels of activin B but did not affect FSH production. We also examined the effect of this p.Met360Thr and an additional INHBB variant (c.314C>T: p.Thr105Met) found in another infertile man on inhibin B and activin B in vitro biosynthesis. We found that both INHBB variants resulted in a significant disruption to activin B in vitro biosynthesis. Together, this analysis supports that INHBB variants that limit activin B production have consequences for testis composition in males.
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