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Record W2074820551 · doi:10.1073/pnas.1323416111

TAp73 is required for spermatogenesis and the maintenance of male fertility

2014· article· en· W2074820551 on OpenAlexafffund
Satoshi Inoue, Richard Tomasini, Alessandro Rufini, Andrew Elia, Massimiliano Agostini, Ivano Amelio, Dave W. Cescon, David Dinsdale, Lily Zhou, Isaac S. Harris, Sophie Lac, Jennifer Silvester, Wanda Y. Li, Masato Sasaki, Jillian Haight, Anne Brüstle, Andrew Wakeham, Colin McKerlie, Andrea Jurisicova, Gerry Melino, Tak W. Mak

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2014
Typearticle
Languageen
FieldMedicine
TopicReproductive Biology and Fertility
Canadian institutionsMount Sinai HospitalHospital for Sick ChildrenUniversity Health NetworkUniversity of TorontoOntario Institute for Cancer Research
FundersScience and Technology Facilities CouncilCanadian Institutes of Health ResearchUniversità degli Studi di Roma Tor VergataMedical Research CouncilAssociazione Italiana per la Ricerca sul Cancro
KeywordsBiologySpermatogenesisSpermiogenesisGerm cellCell biologySpermatidGene knockdownMale infertilityAndrologyGeneticsGeneInfertilityEndocrinologyMedicine

Abstract

fetched live from OpenAlex

The generation of viable sperm proceeds through a series of coordinated steps, including germ cell self-renewal, meiotic recombination, and terminal differentiation into functional spermatozoa. The p53 family of transcription factors, including p53, p63, and p73, are critical for many physiological processes, including female fertility, but little is known about their functions in spermatogenesis. Here, we report that deficiency of the TAp73 isoform, but not p53 or ΔNp73, results in male infertility because of severe impairment of spermatogenesis. Mice lacking TAp73 exhibited increased DNA damage and cell death in spermatogonia, disorganized apical ectoplasmic specialization, malformed spermatids, and marked hyperspermia. We demonstrated that TAp73 regulates the mRNA levels of crucial genes involved in germ stem/progenitor cells (CDKN2B), spermatid maturation/spermiogenesis (metalloproteinase and serine proteinase inhibitors), and steroidogenesis (CYP21A2 and progesterone receptor). These alterations of testicular histology and gene expression patterns were specific to TAp73 null mice and not features of mice lacking p53. Our work provides previously unidentified in vivo evidence that TAp73 has a unique role in spermatogenesis that ensures the maintenance of mitotic cells and normal spermiogenesis. These results may have implications for the diagnosis and management of human male infertility.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.349
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.003
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.052
GPT teacher head0.320
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations93
Published2014
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicReproductive Biology and FertilityFrench-language works237,207