ArticleBiology of reproduction2012
The autoimmune regulator prevents premature reproductive senescence in female mice.
Article in Biology of reproduction, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Genetic associations with diminished ovarian reserve: a systematic review of the literature.Journal of assisted reproduction and genetics · 2014Pooled it
- From Genes to Lives: Integrating the Complexities of Primary Ovarian Insufficiency.International journal of molecular sciences · 2026Review
- Quantitative proteomic analysis of pathological and physiological ovarian aging: model evaluation, molecular mechanisms, and identification of early biomarkers and therapeutic targets.Journal of ovarian research · 2025Article
- Autoimmune regulator deficiency causes sterile epididymitis and impacts male fertility through disruption of inorganic physiology.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Absence of CDK12 in oocyte leads to female infertility.Cell death & disease · 2025Article
- Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence.Life medicine · 2025Review
- Article
- Selected Genetic Factors Associated with Primary Ovarian Insufficiency.International journal of molecular sciences · 2023Review
- Fetal-placental antigens and the maternal immune system: Reproductive immunology comes of age.Immunological reviews · 2022Review
- Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation.The Journal of experimental medicine · 2021Article
- Multiple Lesions Contribute to Infertility in Males Lacking Autoimmune Regulator.The American journal of pathology · 2021Article
- ExtrathymicScience immunology · 2021Article
- TClinical and translational medicine · 2021Article
- The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis.Frontiers in immunology · 2021Review
- Article
- Novel variants in women with premature ovarian function decline identified via whole-exome sequencing.Journal of assisted reproduction and genetics · 2020Article
- Article
- Exploring the Origin and Antigenic Specificity of Maternal Regulatory T Cells in Pregnancy.Frontiers in immunology · 2020Review
- Effects of VEGFStem cell reviews and reports · 2019Article
- Autoimmune Regulator is required in female mice for optimal embryonic development and implantation†.Biology of reproduction · 2019Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in the autoimmune regulator (AIRE) gene are responsible for autoimmune polyglandular syndrome type 1 (APS-1), which commonly manifests as infertility in women. AIRE is a transcriptional regulator that promotes expression of tissue-restricted antigens in the thymus, including antigens specific to the ovary. Thymic expression of ovarian genes under AIRE's control may be critical for preventing ovarian autoimmune disease. Because mice lacking Aire are an important APS-1 model, we examined the reproductive properties of female Aire-deficient (Aire(-/-)) mice. Female Aire(-/-) mice on the BALB/c background were examined for reproductive parameters, including fertility, litter sizes, and ovarian follicular reserves. Although delayed puberty was observed in Aire(-/-) mice, all mice entered puberty and exhibited mating behavior. Only 50% of Aire(-/-) females gave an initial litter, and only 16% were able to produce two litters. Ovarian histopathologic examination revealed that 83% of previously bred females lost all ovarian follicular reserves. Among virgin females, follicular depletion was observed in 25% by 8 wk, and by 20 wk, 50%-60% of mice lost all follicles. This was associated with elevated serum follicle-stimulating hormone level and ovarian infiltration of proliferating CD3+ T lymphocytes. Ovulation rates of 6-wk-old Aire(-/-) mice were reduced by 22%, but this difference was not statistically significant. Finally, transplantation experiments revealed that follicular loss depended on factors extrinsic to the ovary. These results suggest that immune-mediated ovarian follicular depletion is a mechanism of infertility in Aire(-/-) mice. The results have important implications in the pathogenesis of ovarian autoimmune disease in women.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.