ArticleEndocrinology2014
Loss of Ntrk2/Kiss1r signaling in oocytes causes premature ovarian failure.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- Interactions Between Neurotrophins and Ovarian Steroids in Endometriosis and Their Implications for Neuroangiogenesis: A Narrative Review.Current issues in molecular biology · 2026Review
- BDNF Promotes In Vitro Maturation of Sheep Oocytes by Alleviating Oxidative Stress and Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Serum kisspeptin levels in pregnant and non-pregnant diestrus bitches: a pilot study.Frontiers in veterinary science · 2026Article
- Transcriptome Sequencing and Differential Analysis of Ovaries Across Diverse States (Follicular and Non-Follicular Phases).Animals : an open access journal from MDPI · 2025Article
- The kisspeptin analog C6 reverses reproductive dysfunction in a mouse model of hyperprolactinemia.Reproduction (Cambridge, England) · 2025Article
- Hypothalamic FTO upregulates BDNF to promote GnRH expression through the PI3K/Akt pathway, leading to precocious puberty.Frontiers in endocrinology · 2025Article
- Deletion of Nuclear Progesterone Receptors From Kisspeptin Cells Does Not Impair Negative Feedback in Female Mice.Endocrinology · 2024Article
- HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy.Theranostics · 2024Article
- Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients.Frontiers in physiology · 2023Review
- Classical music restored fertility status in rat model of premature ovarian failure.BMC complementary medicine and therapies · 2022Article
- Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure.Human reproduction (Oxford, England) · 2022Article
- TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice.Nature communications · 2022Article
- The role of Kisspeptin signaling in Oocyte maturation.Frontiers in endocrinology · 2022Review
- KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene ExpressionFrontiers in cell and developmental biology · 2022Article
- LncRNA DLEU1 is overexpressed in premature ovarian failure and sponges miR-146b-5p to increase granulosa cell apoptosis.Journal of ovarian research · 2021Article
- Article
- Genome-wide association study and pathway analysis identify NTRK2 as a novel candidate gene for litter size in sheep.PloS one · 2021Article
- Peripheral action of kisspeptin at reproductive tissues-role in ovarian function and embryo implantation and relevance to assisted reproductive technology in livestock: a review.Biology of reproduction · 2020Review
- Exploring the roles of fecundity-related long non-coding RNAs and mRNAs in the adrenal glands of small-tailed Han Sheep.BMC genetics · 2020Article
- Serum and follicular fluid levels of serotonin, kisspeptin, and brain-derived neurotrophic factor in patients undergoingThe Journal of international medical research · 2020Observational
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Neurotrophins (NTs), once believed to be neural-specific trophic factors, are now known to also provide developmental cues to non-neural cells. In the ovary, NTs contribute to both the formation and development of follicles. Here we show that oocyte-specific deletion of the Ntrk2 gene that encodes the NTRK2 receptor (NTRK2) for neurotrophin-4/5 and brain-derived neurotrophic factor (BDNF) results in post-pubertal oocyte death, loss of follicular organization, and early adulthood infertility. Oocytes lacking NTRK2 do not respond to gonadotropins with activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mediated signaling. Before puberty, oocytes only express a truncated NTRK2 form (NTRK2.T1), but at puberty full-length (NTRK2.FL) receptors are rapidly induced by the preovulatory gonadotropin surge. A cell line expressing both NTRK2.T1 and the kisspeptin receptor (KISS1R) responds to BDNF stimulation with activation of Ntrk2 expression only if kisspeptin is present. This suggests that BDNF and kisspeptin that are produced by granulosa cells (GCs) of periovulatory follicles act in concert to mediate the effect of gonadotropins on Ntrk2 expression in oocytes. In keeping with this finding, the oocytes of NTRK2-intact mice fail to respond to gonadotropins with increased Ntrk2 expression in the absence of KISS1R. Our results demonstrate that the preovulatory gonadotropin surge promotes oocyte survival at the onset of reproductive cyclicity by inducing oocyte expression of NTRK2.FL receptors that set in motion an AKT-mediated survival pathway. They also suggest that gonadotropins activate NTRK2.FL expression via a dual communication pathway involving BDNF and kisspeptin produced in GCs and their respective receptors NTRK2.T1 and KISS1R expressed in oocytes.
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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.