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Prenatal Exposure to DEHP Affects Spermatogenesis and Sperm DNA Methylation in a Strain-Dependent Manner.

Prados J, Stenz L, Somm E, Stouder C, Dayer A, Paoloni-Giacobino A - PLoS ONE (2015)

Bottom Line: Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents.The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N.In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain.

View Article: PubMed Central - PubMed

Affiliation: Department of Mental Health and Psychiatry, Division of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.

ABSTRACT
Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents. Here we investigated the impact of prenatal exposure to DEHP on spermatogenesis and DNA sperm methylation in two distinct, selected, and sequenced mice strains. FVB/N and C57BL/6J mice were orally exposed to 300 mg/kg/day of DEHP from gestation day 9 to 19. Prenatal DEHP exposure significantly decreased spermatogenesis in C57BL/6J (fold-change = 0.6, p-value = 8.7*10-4), but not in FVB/N (fold-change = 1, p-value = 0.9). The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N. At the promoter level, three important subsets of genes were massively affected. Promoters of vomeronasal and olfactory receptors coding genes globally followed the same trend, more pronounced in the C57BL/6J strain, of being hyper-methylated in DEHP related conditions. In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain. We additionally analyze both the presence of functional genetic variations within genes that were associated with the detected DMRs and that could be involved in spermatogenesis, and DMRs related with the DEHP exposure that affected both strains in an opposite manner. The major finding in this study indicates that prenatal exposure to DEHP can decrease spermatogenesis in a strain-dependent manner and affects sperm DNA methylation in promoters of large sets of genes putatively involved in both sperm chemotaxis and post-transcriptional regulatory mechanisms.

No MeSH data available.


Related in: MedlinePlus

Production of spermatozoa in 8 weeks-old F1 males prenatally exposed to DEHP.Histogram plot showing on the y-axis the spermatozoa count expressed as millions spermatozoa per milliliters (mio/ml) recorded from sperm of F1 males mice, and on the x-axis, the two genetic backgrounds studied with either prenatal exposure to 300 mg/kg/day DEHP diluted in corn oil (gray bars), or corn oil vehicle only (white bars). Prenatal exposure consists of oral administration during pregnancy days 9 to 19 to the pregnant mice childbearing the future F1 males. Errors bars represent standards deviation. *Statistical significant T-test performed between counts recorded in C57BL/6J controls compared with C57BL/6J DEHP treated (Mean C57BL/6J CTL = 21.3, mean C57BL/6J DEHP 300 = 12.1, t = 5, df = 8, p-value = 8.7*10−4).
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pone.0132136.g001: Production of spermatozoa in 8 weeks-old F1 males prenatally exposed to DEHP.Histogram plot showing on the y-axis the spermatozoa count expressed as millions spermatozoa per milliliters (mio/ml) recorded from sperm of F1 males mice, and on the x-axis, the two genetic backgrounds studied with either prenatal exposure to 300 mg/kg/day DEHP diluted in corn oil (gray bars), or corn oil vehicle only (white bars). Prenatal exposure consists of oral administration during pregnancy days 9 to 19 to the pregnant mice childbearing the future F1 males. Errors bars represent standards deviation. *Statistical significant T-test performed between counts recorded in C57BL/6J controls compared with C57BL/6J DEHP treated (Mean C57BL/6J CTL = 21.3, mean C57BL/6J DEHP 300 = 12.1, t = 5, df = 8, p-value = 8.7*10−4).

Mentions: The number of sperm cells expressed as millions spermatozoa per milliliters (mio/ml) decreased in a statistically significant manner upon DEHP exposure at 300 mg/kg/day in C57BL/6J strain as compared with controls (Mean CTL = 21.3, mean DEHP 300 = 12.1, t = 5.043, df = 8.384, p-value = 8.7*10−4), and the difference between the means was two-fold higher than the delta threshold of 4.4 determined by the power T-test (Fig 1). No effect of DEHP could be detected on the number of sperm cells in the FVB/N strain at 300 mg/kg/day (mean CTL = 17.96, mean DEHP 300 = 17.80, t = 0.13, df = 11, p-value = 0.9).


Prenatal Exposure to DEHP Affects Spermatogenesis and Sperm DNA Methylation in a Strain-Dependent Manner.

Prados J, Stenz L, Somm E, Stouder C, Dayer A, Paoloni-Giacobino A - PLoS ONE (2015)

Production of spermatozoa in 8 weeks-old F1 males prenatally exposed to DEHP.Histogram plot showing on the y-axis the spermatozoa count expressed as millions spermatozoa per milliliters (mio/ml) recorded from sperm of F1 males mice, and on the x-axis, the two genetic backgrounds studied with either prenatal exposure to 300 mg/kg/day DEHP diluted in corn oil (gray bars), or corn oil vehicle only (white bars). Prenatal exposure consists of oral administration during pregnancy days 9 to 19 to the pregnant mice childbearing the future F1 males. Errors bars represent standards deviation. *Statistical significant T-test performed between counts recorded in C57BL/6J controls compared with C57BL/6J DEHP treated (Mean C57BL/6J CTL = 21.3, mean C57BL/6J DEHP 300 = 12.1, t = 5, df = 8, p-value = 8.7*10−4).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526524&req=5

pone.0132136.g001: Production of spermatozoa in 8 weeks-old F1 males prenatally exposed to DEHP.Histogram plot showing on the y-axis the spermatozoa count expressed as millions spermatozoa per milliliters (mio/ml) recorded from sperm of F1 males mice, and on the x-axis, the two genetic backgrounds studied with either prenatal exposure to 300 mg/kg/day DEHP diluted in corn oil (gray bars), or corn oil vehicle only (white bars). Prenatal exposure consists of oral administration during pregnancy days 9 to 19 to the pregnant mice childbearing the future F1 males. Errors bars represent standards deviation. *Statistical significant T-test performed between counts recorded in C57BL/6J controls compared with C57BL/6J DEHP treated (Mean C57BL/6J CTL = 21.3, mean C57BL/6J DEHP 300 = 12.1, t = 5, df = 8, p-value = 8.7*10−4).
Mentions: The number of sperm cells expressed as millions spermatozoa per milliliters (mio/ml) decreased in a statistically significant manner upon DEHP exposure at 300 mg/kg/day in C57BL/6J strain as compared with controls (Mean CTL = 21.3, mean DEHP 300 = 12.1, t = 5.043, df = 8.384, p-value = 8.7*10−4), and the difference between the means was two-fold higher than the delta threshold of 4.4 determined by the power T-test (Fig 1). No effect of DEHP could be detected on the number of sperm cells in the FVB/N strain at 300 mg/kg/day (mean CTL = 17.96, mean DEHP 300 = 17.80, t = 0.13, df = 11, p-value = 0.9).

Bottom Line: Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents.The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N.In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain.

View Article: PubMed Central - PubMed

Affiliation: Department of Mental Health and Psychiatry, Division of Psychiatric Specialties, University Hospitals of Geneva, Geneva, Switzerland; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.

ABSTRACT
Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents. Here we investigated the impact of prenatal exposure to DEHP on spermatogenesis and DNA sperm methylation in two distinct, selected, and sequenced mice strains. FVB/N and C57BL/6J mice were orally exposed to 300 mg/kg/day of DEHP from gestation day 9 to 19. Prenatal DEHP exposure significantly decreased spermatogenesis in C57BL/6J (fold-change = 0.6, p-value = 8.7*10-4), but not in FVB/N (fold-change = 1, p-value = 0.9). The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N. At the promoter level, three important subsets of genes were massively affected. Promoters of vomeronasal and olfactory receptors coding genes globally followed the same trend, more pronounced in the C57BL/6J strain, of being hyper-methylated in DEHP related conditions. In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain. We additionally analyze both the presence of functional genetic variations within genes that were associated with the detected DMRs and that could be involved in spermatogenesis, and DMRs related with the DEHP exposure that affected both strains in an opposite manner. The major finding in this study indicates that prenatal exposure to DEHP can decrease spermatogenesis in a strain-dependent manner and affects sperm DNA methylation in promoters of large sets of genes putatively involved in both sperm chemotaxis and post-transcriptional regulatory mechanisms.

No MeSH data available.


Related in: MedlinePlus