ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 61 citations in OpenAlex.
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- Lactylation of CREB is required for FSH-induced proliferation and differentiation of ovarian granulosa cells.Nucleic acids research · 2025Article
- Pyruvate Regulates the Expression ofCells · 2025Article
- Progressive Deactivation of Hydroxylases Controls Hypoxia-Inducible Factor-1α-Coordinated Cellular Adaptation to Graded Hypoxia.Research (Washington, D.C.) · 2025Article
- Lactate Promotes Hypoxic Granulosa Cells' Autophagy by Activating the HIF-1α/BNIP3/Beclin-1 Signaling Axis.Genes · 2024Article
- Delineating lipidomic landscapes in human and mouse ovaries: Spatial signatures and chemically-induced alterations via MALDI mass spectrometry imaging: Spatial ovarian lipidomics.Environment international · 2024Article
- Enhanced solute transport and steady mechanical stimulation in a novel dynamic perifusion bioreactor increase the efficiency of theFrontiers in bioengineering and biotechnology · 2024Article
- Glucose and redox metabolism in meiotically blocked in vitro grown mouse antral follicles.Journal of assisted reproduction and genetics · 2023Article
- Dynamic in vitro culture of bovine and human ovarian tissue enhances follicle progression and health.Scientific reports · 2023Article
- Recapitulating folliculogenesis and oogenesis outside the body: encapsulated in vitro follicle growth†.Biology of reproduction · 2023Article
- Advanced bioengineering of female germ cells to preserve fertility.Biology of reproduction · 2022Review
- Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling.Cell death & disease · 2022Article
- Kidney-Targeted Delivery of Prolyl Hydroxylase Domain Protein 2 Small Interfering RNA with Nanoparticles Alleviated Renal Ischemia/Reperfusion Injury.The Journal of pharmacology and experimental therapeutics · 2021Article
- Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway.Reproductive biology and endocrinology : RB&E · 2020Article
- Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome.Frontiers in immunology · 2020Article
- TRIB3 Promotes Lung Adenocarcinoma Progression via an Enhanced Warburg Effect.Cancer management and research · 2020Article
- Lessons from bioengineering the ovarian follicle: a personal perspective.Reproduction (Cambridge, England) · 2019Review
- Mitochondrial Toxicity of Azithromycin Results in Aerobic Glycolysis and DNA Damage of Human Mammary Epithelia and Fibroblasts.Antibiotics (Basel, Switzerland) · 2019Article
- Cell-free DNA in medium is associated with the maturation ability of in vitro cultured oocytes.The Journal of reproduction and development · 2019Article
- Prenatal retinoic acid exposure reveals candidate genes for craniofacial disorders.Scientific reports · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Oxygen tension is critical for follicle growth and metabolism, especially for early-stage follicles, where vascularity is limited. Its role and underlying mechanism in the in vitro activation and maturation of immature to ovulatory follicles is largely unknown. In this study, early secondary (110 μm) murine follicles were isolated and encapsulated in alginate hydrogels to replicate the in vivo environment of the growing/maturing follicle. Encapsulated follicles were cultured for 8 days at either 2.5 or 20% O2. Survival (2.6-fold) and growth (1.2-fold) were significantly higher for follicles cultured at 2.5% compared with 20% O2. Using a mouse hypoxia-signaling pathway qRT-PCR array and GeneGo Metacore analysis, we found that direct target genes of the hypoxia-activated HIF1-complex were significantly upregulated in follicles cultured for 8 days at 2.5% compared with 20% O2, including the carbohydrate transport and metabolism genes Slc2a3, Vegfa, Slc2a1, Edn1, Pgk1, Ldha, and Hmox1. Other upregulated genes included carbohydrate transporters (Slc2a1, Slc2a3, and Slc16a3) and enzymes essential for glycolysis (Pgk1, Hmox1, Hk2, Gpi1, Pfkl, Pfkp, Aldoa, Gapdh, Pgam1, Eno1, Pkm2, and Ldha). For follicles cultured at 2.5% O2, a 7.2-fold upregulation of Vegfa correlated to an 18-fold increase in VEGFA levels, and a 3.2-fold upregulation of Ldha correlated to a 4.8-fold increase in lactate levels. Both VEGFA and lactate levels were significantly higher in follicles cultured at 2.5% compared with 20% O2. Therefore, enhanced hypoxia-mediated glycolysis is essential for growth and survival of early secondary follicles and provides vital insights into improving in vitro culture conditions.
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Registered trials
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