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Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice.

Guerrero-Bosagna CM, Sabat P, Valdovinos FS, Valladares LE, Clark SJ - BMC Physiol. (2008)

Bottom Line: Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females).Acta1 is known to be developmentally regulated and related to morphomotric features.This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA, 99164-4231, USA. guerrerobosagna@gmail.com

ABSTRACT

Background: Developmental effects of exposure to endocrine disruptors can influence adult characters in mammals, but could also have evolutionary consequences. The aim of this study was to simulate an environmental exposure of an experimental population of mice to high amounts of nutritional phytoestrogens and to evaluate parameters of relevance for evolutionary change in the offspring. The effect of a continuous pre- and post-natal exposure to high levels of dietary isoflavones was evaluated on sexual maturity, morphometric parameters and DNA methylation status in mice. Adult mice male/female couples were fed ad libitum either with control diet (standard laboratory chow) or ISF diet (control diet plus a soy isoflavone extract at 2% (w/w) that contained the phytoestrogens genistein and daidzein). In the offspring we measured: i) the onset of vaginal opening (sexual maturation) in females, ii) weight and size in all pups at 7, 14, 21 and 42 days post-natal (dpn) and iii) DNA methylation patterns in skeletal alpha-actin (Acta1), estrogen receptor-alpha and c-fos in adults (42 dpn).

Results: Vaginal opening was advanced in female pups in the ISF group, from 31.6 +/- 0.75 dpn to 25.7 +/- 0.48. No differences in size or weight at ages 7, 14 or 21 dpn were detected between experimental groups. Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females). Also, natural differences seen in DNA methylation at Acta1 promoter in the offspring originated in the control group were suppressed in the ISF group. Acta1 is known to be developmentally regulated and related to morphomotric features.

Conclusion: This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.

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Comparison of morphometric parameters between pups 42 days old. Variation in adult weight and size observed in the offspring of a population of mice subjected to ISF or control diet is shown. (a) indicates the general trend of decreased size (P = 0.03, *) and weight (P = 0.06, #) in the ISF group with regard to controls, when pooling males and females. Size differences in (a) are explained by variations in both sexes, as shown in (b). Weight differences in (a) are accounted for by variations only in males, which are heavier in the control group than in the ISF group (P = 0.04, ‡), as can be seen in (c). Also, in the control group males are heavier that females (P < 0.001; c, right, ±), difference that is suppressed in the ISF group (P = 0.3; c, left).
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Figure 4: Comparison of morphometric parameters between pups 42 days old. Variation in adult weight and size observed in the offspring of a population of mice subjected to ISF or control diet is shown. (a) indicates the general trend of decreased size (P = 0.03, *) and weight (P = 0.06, #) in the ISF group with regard to controls, when pooling males and females. Size differences in (a) are explained by variations in both sexes, as shown in (b). Weight differences in (a) are accounted for by variations only in males, which are heavier in the control group than in the ISF group (P = 0.04, ‡), as can be seen in (c). Also, in the control group males are heavier that females (P < 0.001; c, right, ±), difference that is suppressed in the ISF group (P = 0.3; c, left).

Mentions: When pooling males and females, no differences were detected in the offspring among experimental groups in size or weight at ages 7, 14 or 21 dpn. However, reduced size (P = 0.03) and weight (P = 0.06) (2-way ANOVA; nISF = 19, nCONTROL = 24) were observed at age 42 dpn in the ISF group (Fig. 4a). Contribution of both sexes variation account for size differences observed, as shown in Figure 4b, because no significant changes were detected independently for each gender (males, P = 0.09, Students t test; nISF = 9, nCONTROL = 12; females, P = 0.19, Students t test; nISF = 10, nCONTROL = 12). Weight differences, in turn, are accounted for by variations only in males (P = 0.04, Students t test; nISF = 9, nCONTROL = 12), but not in females (P = 0.8, Students t test; nISF = 10, nCONTROL = 12), as seen in Figure 4c. Thus, normal gender differences in weight seen in the control group (males heavier that females, P < 0.001; Student's t test; nFEMALES = 12, nMALES = 12; Fig. 4c, right) are suppressed in the ISF group (P = 0.3; Student's t test; nFEMALES = 10, nMALES = 9; Fig. 4c, left). Finally, no differences were detected among experimental groups in ano-genital distance for either males or females.


Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice.

Guerrero-Bosagna CM, Sabat P, Valdovinos FS, Valladares LE, Clark SJ - BMC Physiol. (2008)

Comparison of morphometric parameters between pups 42 days old. Variation in adult weight and size observed in the offspring of a population of mice subjected to ISF or control diet is shown. (a) indicates the general trend of decreased size (P = 0.03, *) and weight (P = 0.06, #) in the ISF group with regard to controls, when pooling males and females. Size differences in (a) are explained by variations in both sexes, as shown in (b). Weight differences in (a) are accounted for by variations only in males, which are heavier in the control group than in the ISF group (P = 0.04, ‡), as can be seen in (c). Also, in the control group males are heavier that females (P < 0.001; c, right, ±), difference that is suppressed in the ISF group (P = 0.3; c, left).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2556694&req=5

Figure 4: Comparison of morphometric parameters between pups 42 days old. Variation in adult weight and size observed in the offspring of a population of mice subjected to ISF or control diet is shown. (a) indicates the general trend of decreased size (P = 0.03, *) and weight (P = 0.06, #) in the ISF group with regard to controls, when pooling males and females. Size differences in (a) are explained by variations in both sexes, as shown in (b). Weight differences in (a) are accounted for by variations only in males, which are heavier in the control group than in the ISF group (P = 0.04, ‡), as can be seen in (c). Also, in the control group males are heavier that females (P < 0.001; c, right, ±), difference that is suppressed in the ISF group (P = 0.3; c, left).
Mentions: When pooling males and females, no differences were detected in the offspring among experimental groups in size or weight at ages 7, 14 or 21 dpn. However, reduced size (P = 0.03) and weight (P = 0.06) (2-way ANOVA; nISF = 19, nCONTROL = 24) were observed at age 42 dpn in the ISF group (Fig. 4a). Contribution of both sexes variation account for size differences observed, as shown in Figure 4b, because no significant changes were detected independently for each gender (males, P = 0.09, Students t test; nISF = 9, nCONTROL = 12; females, P = 0.19, Students t test; nISF = 10, nCONTROL = 12). Weight differences, in turn, are accounted for by variations only in males (P = 0.04, Students t test; nISF = 9, nCONTROL = 12), but not in females (P = 0.8, Students t test; nISF = 10, nCONTROL = 12), as seen in Figure 4c. Thus, normal gender differences in weight seen in the control group (males heavier that females, P < 0.001; Student's t test; nFEMALES = 12, nMALES = 12; Fig. 4c, right) are suppressed in the ISF group (P = 0.3; Student's t test; nFEMALES = 10, nMALES = 9; Fig. 4c, left). Finally, no differences were detected among experimental groups in ano-genital distance for either males or females.

Bottom Line: Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females).Acta1 is known to be developmentally regulated and related to morphomotric features.This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA, 99164-4231, USA. guerrerobosagna@gmail.com

ABSTRACT

Background: Developmental effects of exposure to endocrine disruptors can influence adult characters in mammals, but could also have evolutionary consequences. The aim of this study was to simulate an environmental exposure of an experimental population of mice to high amounts of nutritional phytoestrogens and to evaluate parameters of relevance for evolutionary change in the offspring. The effect of a continuous pre- and post-natal exposure to high levels of dietary isoflavones was evaluated on sexual maturity, morphometric parameters and DNA methylation status in mice. Adult mice male/female couples were fed ad libitum either with control diet (standard laboratory chow) or ISF diet (control diet plus a soy isoflavone extract at 2% (w/w) that contained the phytoestrogens genistein and daidzein). In the offspring we measured: i) the onset of vaginal opening (sexual maturation) in females, ii) weight and size in all pups at 7, 14, 21 and 42 days post-natal (dpn) and iii) DNA methylation patterns in skeletal alpha-actin (Acta1), estrogen receptor-alpha and c-fos in adults (42 dpn).

Results: Vaginal opening was advanced in female pups in the ISF group, from 31.6 +/- 0.75 dpn to 25.7 +/- 0.48. No differences in size or weight at ages 7, 14 or 21 dpn were detected between experimental groups. Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females). Also, natural differences seen in DNA methylation at Acta1 promoter in the offspring originated in the control group were suppressed in the ISF group. Acta1 is known to be developmentally regulated and related to morphomotric features.

Conclusion: This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.

Show MeSH
Related in: MedlinePlus