Fig. 7: Advanced maternal age impairs embryo telomere elongation that is restored by preconception treatment with mitochondria-acting therapeutics.
From: Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization
Female mice that were reproductively aged (12 months old) and young (3-4 months) controls were treated with BGP-15 (100 mg/kg) or saline vehicle before ovulation, IVF and embryo assessments (a) Created in BioRender. Gordon, Y. (2025) https://BioRender.com/c74d013. Zygotes were labelled with MitoSox Red (red, and Hoechst-3342 (blue)); and red fluorescence measured (b; n = 21 young, n = 12 aged, n = 10 aged+BGP-15). Morulae were stained with TMRM (red) and Hoechst-3342 (blue) and red fluorescence measured (c; n = 3 young, n = 20 young+BGP-15, n = 14 aged, n = 8 aged+BGP-15). Telomere length per cell (telomere/ Rn18s (2-ΔΔCt)) in individual MII oocytes of young vs 12-month-old mice (d; n = 108 young, n = 66 aged); as well as oocytes from 12 month old mice that were nulliparous vs multiparous (e; n = 46 nulliparous, n = 37 multiparous). Telomere length per cell in individual 8-cell embryos (f; n = 36 young, n = 33 young+BGP-15, n = 19 aged, n = 44 aged+BGP-15), whole blastocysts (g; n = 31 young, n = 10 aged, n = 24 aged+BGP-15) and isolated ICM (h; n = 12 young, n = 19 aged, n = 20 aged+BGP-15). Metformin (2 mg/mL) or MitoQ (150 µM) was administered in drinking water to reproductively aged females for two weeks prior to gonadotropin stimulation and IVF of ovulated oocytes (i) Created in BioRender. Gordon, Y. (2025) https://BioRender.com/m49j079. Zygotes were labelled with MitoSox Red (red, and Hoechst-3342 (blue)); and red fluorescence measured (j; n = 20 young, n = 31 aged, n = 21 aged+Metformin, n = 20 aged+MitoQ). Telomere length in individual ICMs (k; n = 47 young, n = 19 aged, n = 25 aged+Metformin, n = 16 aged+MitoQ). Individual data points are plotted, horizontal lines are mean ± SEM (b, c, j). Violin plots show population distribution, and horizontal lines are mean ± SEM. qPCR data was log transformed for statistical analysis. Statistical tests were one-way ANOVA (b, c, f-h, j, k) or two-sided unpaired t-test (d, e); *p < 0.05, **p ≤ 0.0095, ****p < 0.0001. For exact P values see Supplementary Table 7. Representative images shown, scale bar: 20 µm (b, c, j). Source data are provided as a Source Data File.
