Evidence map›Paper›PMID 40102860›Full record

ArticleReproductive biology and endocrinology : RB&E2025

FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development.

Laura Danti, Karolina Lundin, Petra Nedeczey-Ruzsák, Timo Tuuri, Juha S Tapanainen

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Article in Reproductive biology and endocrinology : RB&E, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Canine XX Disorders/Differences of Sex Development (SRY-Negative): A Potential Role for theSexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026
    Review
4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Laura DantiDepartment of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Helsinki, 00029 HUS, Finland.
Karolina LundinDepartment of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Helsinki, 00029 HUS, Finland. karolina.lundin@helsinki.fi.
Petra Nedeczey-RuzsákDepartment of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Helsinki, 00029 HUS, Finland.
Timo Tuuri *Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Helsinki, 00029 HUS, Finland.
Juha S Tapanainen *Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Helsinki, 00029 HUS, Finland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundForkhead box L2 (FOXL2) is a transcription factor from the forkhead box family primarily expressed in the pituitary, ovaries, and eyelids. Human mutations in FOXL2 cause blepharophimosis, ptosis, epicanthus and inversus syndrome (BPES), which can be associated with primary ovarian insufficiency, and is indirectly linked with differences of sex development (DSD). Animal studies have shown the crucial role that FOXL2 plays in the development, function, and maintenance of the ovary as well as in sex determination. However, the specific role of FOXL2 in early human somatic cell ovarian development is largely unknown.

methodsIn this study, we utilised CRISPR/Cas9 genome activation and a previously published in-house 14-day gonadal differentiation protocol to study the role of FOXL2.

resultsOur results demonstrate that FOXL2 downregulates coelomic epithelial markers GATA4 and LHX9, female gonadal markers RSPO1 and WNT4, and male gonadal markers SOX9, NR0B1 and DHH. The differentially expressed genes were mostly associated with Kyoto encyclopaedia of genes and genomes (KEGG) pathways relating to cell adhesion molecules and gene ontology (GO) pathways relating to extracellular matrix and junction formation. Furthermore, a comparative analysis with existing single cell RNA sequencing data from human in vivo-derived samples elucidated that FOXL2 initiates the downregulation of coelomic epithelial genes GATA4, LHX9 and UPK3B at day 6. By day 8, the genes ARX and GATA2 are transiently upregulated by FOXL2 induction and then downregulated as the genes LGR5, TSPAN8, OSR1 and TAC1 become upregulated.

conclusionsThese findings suggest that FOXL2 facilitates the exit of differentiating cells from the coelomic epithelium and initially drives them towards a transitional identity before progressing into early supporting gonadal-like cells. The findings of this study significantly advance our understanding of normal gonadal development which can be used as a basis to elucidate pathological gonadal development underlying BPES.

Indexed as

Cell DifferentiationForkhead Box Protein L2OvaryFemaleGene Expression Regulation, DevelopmentalHumansMaleSex DifferentiationForkhead Box Protein L2FOXL2 protein, humanCRISPR/Cas9FOXL2Granulosa cellOvaryStem cells

Identifiers

PMID40102860
PMCPMC11917015

What Socratic holds

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Registered trials

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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 Socratic graph.