ArticleThe Journal of experimental medicine2013
Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Programs to Strengthen Parent-Adolescent Communication About Reproductive Health: A Systematic Review.American journal of preventive medicine · 2015Pooled it
- The role of the cGAS-STING pathway in male reproductive disorders.Molecular biology reports · 2026Review
- The Emerging Roles of Protein Lipidation in Fertility and Reproductive Disorders: Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- CpG Methylation of Protein Prenyltransferase GenesEpigenomes · 2026Article
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- NPC1 as a novel therapeutic target for induction of pyroptosis in cancers.Biomarker research · 2025Article
- Geranylgeranyl diphosphate synthase deficiency impairs efferocytosis and resolution of acute lung injury.Respiratory research · 2025Article
- The consequences of climate change and male reproductive health: A review of the possible impact and mechanisms.Biochemistry and biophysics reports · 2025Review
- A Comprehensive Bibliometric Analysis of Orchitis Research from 1980 to 2023.Advances in experimental medicine and biology · 2025Review
- Molecular mechanisms of cellular dysfunction in testes from men with non-obstructive azoospermia.Nature reviews. Urology · 2024Review
- MGenes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Article
- Fumigaclavine C ameliorates liver steatosis by attenuating hepatic de novo lipogenesis via modulation of the RhoA/ROCK signaling pathway.BMC complementary medicine and therapies · 2023Article
- Targeting the mevalonate pathway suppresses ARID1A-inactivated cancers by promoting pyroptosis.Cancer cell · 2023Article
- DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome.Frontiers in immunology · 2023Article
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Single intratesticular injection of blood-serum-derived exosomes can potentially alleviate testopathy following testicular torsion.Animal models and experimental medicine · 2022Article
- Knockout of GGPPS1 restrains rab37-mediated autophagy in response to ventilator-induced lung injury.Human cell · 2022Article
- New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder.Human genetics · 2022Review
- Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction.Journal of molecular cell biology · 2021Article
- Severe Acute Respiratory Syndrome Coronavirus 2 and Male Reproduction: Relationship, Explanations, and Clinical Remedies.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mumps commonly affects children 5-9 yr of age, and can lead to permanent adult sterility in certain cases. However, the etiology of this long-term effect remains unclear. Mumps infection results in progressive degeneration of the seminiferous epithelium and, occasionally, Sertoli cell-only syndrome. Thus, the remaining Sertoli cells may be critical to spermatogenesis recovery after orchitis healing. Here, we report that the protein farnesylation/geranylgeranylation balance is critical for patients' fertility. The expression of geranylgeranyl diphosphate synthase 1 (GGPPS) was decreased due to elevated promoter methylation in the testes of infertile patients with mumps infection history. When we deleted GGPPS in mouse Sertoli cells, these cells remained intact, whereas the adjacent spermatogonia significantly decreased after the fifth postnatal day. The proinflammatory MAPK and NF-κB signaling pathways were constitutively activated in GGPPS(-/-) Sertoli cells due to the enhanced farnesylation of H-Ras. GGPPS(-/-) Sertoli cells secreted an array of cytokines to stimulate spermatogonia apoptosis, and chemokines to induce macrophage invasion into the seminiferous tubules. Invaded macrophages further blocked spermatogonia development, resulting in a long-term effect through to adulthood. Notably, this defect could be rescued by GGPP administration in EMCV-challenged mice. Our results suggest a novel mechanism by which mumps infection during childhood results in adult sterility.
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