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Axin-1, a negative regulator of Wnt signaling, is a versatile scaffold protein involved in centrosome separation and spindle assembly in mitosis, but its function in mammalian oogenesis remains unknown. Here we examined the localization and function of Axin-1 during meiotic maturation in mouse oocytes. Immunofluorescence analysis showed that Axin-1 was localized around the spindle. Knockdown of the Axin1 gene by microinjection of specific short interfering (si)RNA into the oocyte cytoplasm resulted in severely defective spindles, misaligned chromosomes, failure of first polar body (PB1) extrusion, and impaired pronuclear formation. However, supplementing the culture medium with the Wnt pathway activator LiCl improved spindle morphology and pronuclear formation. Downregulation of Axin1 gene expression also impaired the spindle pole localization of γ-tubulin/Nek9 and resulted in retention of the spindle assembly checkpoint protein BubR1 at kinetochores after 8.5 h of culture. Our results suggest that Axin-1 is critical for spindle organization and cell cycle progression during meiotic maturation in mouse oocytes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902301 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157197 | PLOS |
FASEB J
September 2025
Faculty of Medicine in Pilsen, Biomedical Center, Charles University, Prague, Czech Republic.
Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional Tfam knockout (Tfam; Zp3-Cre) to produce Tfam oocytes for investigation of the mitochondrial abundance in oocytes and early embryos.
View Article and Find Full Text PDFCell Discov
September 2025
Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
Adverse intrauterine environments, such as hyperglycemia, impair sexual reproduction and species continuity, yet the underlying mechanisms remain poorly understood. In this study, we demonstrated that intrauterine hyperglycemia significantly disrupted primordial germ cell (PGC) development, especially in female offspring, thus reducing fertility. Using Oct4-EGFP transgenic mice with intrauterine hyperglycemia exposure, we revealed that hyperglycemia compromised sexually specific chromatin accessibility and DNA methylation reprogramming during PGC development.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 400-8510 Yamanashi, Japan.
Background: Lysosomes serve not only in the degradation of cellular components but also as calcium (Ca) stores. In this study, we investigated the effects of trans-Ned19, an inhibitor of lysosomal calcium channels known to block two-pore channels (TPCs), on fertilization and oocyte activation in mice.
Methods: Pronuclear formation was assessed via Hoechst 33342 staining, cortical granule release was evaluated using agglutinin-fluorescein isothiocyanate (LCA-FITC) staining, intracellular Ca levels were monitored with Cal-520 AM, and sperm motility was analyzed using a sperm motility analysis system (SMAS).
J Cell Mol Med
September 2025
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Diminished ovarian reserve (DOR) poses significant challenges in reproductive health, with emerging evidence implicating DNA damage repair pathways. While GADD45A is a critical regulator of DNA repair, cell cycle and apoptosis, its role in DOR pathogenesis remains unexplored. We employed transcriptome sequencing, qPCR and Western Blot analyses to compare GADD45A expression in granulosa cells (GCs) between DOR patients and controls.
View Article and Find Full Text PDFMol Hum Reprod
September 2025
Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Antwerp, Belgium.
Maternal diet-induced obesity (DIO) may affect adult offspring oocyte quality due to mitochondrial dysfunction. Here, we investigated whether offspring of DIO mothers exhibit mitochondrial abnormalities in their primordial follicle oocytes (PFOs) already at birth, and if (further) alterations can be detected at weaning. Female Swiss mice were fed a control or obesogenic diet for 7 weeks before mating, and throughout pregnancy and lactation.
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