Figure 1.
Ancestral exposure to methoxychlor and transgenerational kidney disease.
Percentages of females (panel A, C, E) and males (panel B, D, F) with kidney diseases in the F1 and F3 generation control (open bars) and methoxychlor (black bars) lineages. The number of diseased rats / total number of rats in each lineage are also shown (* P<0.05; ** P<0.01).
Figure 2.
Ancestral exposure to methoxychlor and transgenerational pubertal abnormalities, and ovarian and uterine diseases.
Percentages of females F1 and F3 generation (panel A) and males (panel B) with pubertal abnormality or females with ovarian disease (panel C) or uterine infection (panel D). Percentages of the F1 and F3 generation females with primordial follicle loss (panel E) and polycystic ovary disease (panel F) in control and methoxychlor lineages. The number of diseased rats / total number of rats in each lineage are also shown. (** P<0.01; *** P<0.001).
Figure 3.
Ancestral exposure to methoxychlor and transgenerational tumor development and transgenerational obesity.
Percentages of F1 and F3 generation females (panel A) or males (panel B) with tumor development and percentages of females (panel C) or males (panel D) with obesity. Representative abdominal adiposity for obese (panel E) animals is presented with arrows indicating the excessive dorsal abdominal and retro-peritoneal adiposity distribution. The number of diseased rats / total number of rats is shown above the respective bar graphs (** P<0.01).
Figure 4.
Ancestral exposure to methoxychlor and adult-onset transgenerational disease in rats.
Incidences of F1 and F3 generation total female disease (panel A), total male disease (panel B), female multiple disease (panel C) and male multiple disease (panel D) in control and methoxychlor lineages. The number of diseased rats / total number of rats is shown above the respective bar graphs (* P<0.05; ** P<0.01; *** P<0.001).
Figure 5.
Ancestral exposure to methoxychlor promoted adult-onset transgenerational diseases in F4 generation reverse outcross offspring showing female germline transmission.
Incidences of kidney disease in females (panel A), in males (panel B), obesity in females (panel C) and in males (panel D) of the F4 generation outcross (OC) or reverse outcross (ROC) offspring of the control and methoxychlor lineages.
Figure 6.
Ancestral exposure to methoxychlor promoted adult-onset transgenerational diseases in F4 generation reverse outcross offspring increasing total female disease, total male disease and multiple male disease incidences.
Incidences of total disease in females (panel A), in males (panel B), multiple female disease (panel C), and multiple male disease (panel D) in the F4 generation outcross (OC) or reverse outcross (ROC) offspring of the control and methoxychlor lineages.
Figure 7.
Ancestral exposure to methoxychlor and transgenerational epigenetic changes and induced sperm intersection epimutations.
Chromosomal locations for regions with transgenerational change in DNA methylation (arrowheads). There were 37 differentially methylated regions in sperm DNA from methoxychlor lineage rats compared to control lineage rats for all three experiments.
Figure 8.
Ancestral exposure to methoxychlor and transgenerational epigenetic changes and induced sperm average epimutations.
Chromosomal locations for regions with transgenerational change in DNA methylation (arrowheads). There were 311 differentially methylated regions in sperm DNA from methoxychlor lineage rats compared to control lineage rats for all experiments. The box under the line at each chromosome represents a statistically significant over-representation (cluster) of epimutations.
Table 1.
Methoxychlor induced intersection sperm epimutations.
Figure 9.
Exposure specific transgenerational sperm epimutations in methoxychlor, vinclozolin, DDT, pesticide (DEET and permethrin) and plastics (BPA and phthalates).
A Venn diagram indicating the total number of intersection epimutations (A) and average epimutations (B) involving overlap between the various epimutation exposure data sets. Total number of epimutations for each exposure are in brackets next to label.
Table 2.
Pathway DMR associations.