Fig. 9: Maternal obesity impairs embryo and fetal telomere elongation that is restored by pre-conception treatment with mitochondria-acting therapeutics.
From: Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization
Obese female mice ( > 36 g) and lean littermate controls were treated with BGP-15 (100 mg/kg) or saline vehicle prior to ovulation, IVF and analysis of embryos and fetal tissues (a) Created in BioRender. Gordon, Y. (2025) https://BioRender.com/z87s922. Zygotes were labelled with MitoSox Red (red) and Hoechst-3342 (blue) and red fluorescence measured (b; n = 12 lean, n = 11 lean+BGP-15, n = 17 obese, n = 10 obese+BGP-15). 8-cell embryos and morulae were stained with TMRM (red) and Hoechst-3342 (blue) and red fluorescence measured (c; 8-cell: n = 28 lean, n = 23 lean+BGP-15, n = 17 obese, n = 14 obese+BGP-15; morula: n = 11 lean, n = 17 lean+BGP-15, n = 10 obese, n = 7 obese+BGP-15). Telomere length per cell (telomere/ Rn18s (2-ΔΔCt)) was assessed by qPCR in individual MII oocytes (d; n = 250 lean, n = 218 lean+BGP-15, n = 104 obese, n = 100 obese+BGP-15), 8-cell embryos (e; n = 30 lean, n = 50 lean+BGP-15, n = 22 obese, n = 45 obese+BGP-15), whole blastocysts (f; n = 51 lean, n = 16 lean+BGP-15, n = 11 obese, n = 12 obese+BGP-15) and ICM (g; n = 31 lean, n = 24 obese, n = 17 obese+BGP-15). Metformin (2 mg/mL) or MitoQ (150 µM) was administered in drinking water to obese females for two weeks prior to gonadotropin stimulation and IVF of ovulated oocytes. Zygotes were labelled with MitoSox Red (red) and Hoechst-3342 (blue); and red fluorescence measured (h; n = 21 lean, n = 16 obese, n = 19 obese+Metformin, n = 23 obese+MitoQ). Telomere length in individual ICMs (i; n = 57 lean, n = 45 obese, n = 36 obese+Metformin, n = 37 obese+MitoQ). Blastocysts from oocytes of lean, obese, or obese BGP-15-treated (100 mg/kg) mice were transferred to surrogate females for gestation and fetal tissues collected at day 14.5 of pregnancy for qPCR telomere length analysis (telomere/36b4 (2-ΔΔCt)) of liver, kidney, and heart (j; liver: n = 16 lean, n = 17 obese, n = 12 obese+BGP-15; kidney: n = 12 lean, n = 12 obese, n = 10 obese+BGP-15, heart: n = 6 lean, n = 12 obese, n = 11 obese+BGP-15). Individual data points are plotted, horizontal lines are mean ± SEM (b, c, h). Violin plots show population distribution, and horizontal lines are mean ± SEM (d-g, i, j). qPCR data was log transformed for statistical analysis. Data analyzed using one-way ANOVA; *p < 0.05, **p < 0.009, ***p ≤ 0.0007, ****p < 0.0001. For exact P values see Supplementary Table 9. Source data are provided as a Source Data File.
