TY - JOUR
T1 - Prenatal exposure to Di(2-ethylhexyl) phthalate causes long-term transgenerational effects on female reproduction in mice
AU - Brehm, Emily
AU - Rattan, Saniya
AU - Gao, Liying
AU - Flaws, Jodi A.
N1 - This work was supported by National Institutes of Health Grant P01 ES022848 (to J.A.F.), US Environmental Protection Agency Grant RD-83543401 (to J.A.F.), and National Institutes of Health Grant T32 ES007326 (to S.R.).
Financial Support: This work was supported by National Institutes of Health Grant P01 ES022848 (to J.A.F.), US Environmental Protection Agency Grant RD-83543401 (to J.A.F.), and National Institutes of Health Grant T32 ES007326 (to S.R.).
The authors thank the members of J.A.F.’s laboratory for assistance and the University of Virginia Center for Research in Reproduction Ligand Assay & Analysis Core [supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health (National Centers for Translational Research in Reproduction and Infertility) Grant P50-HD28934] for assistance with measuring serum hormone levels.
PY - 2018/2
Y1 - 2018/2
N2 - Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer in many consumer products. Although DEHP is a known endocrine disruptor, little is known about the effects of DEHP exposure on female reproduction. Thus, this study tested the hypothesis that prenatal DEHP exposure affects follicle numbers, estrous cyclicity, and hormone levels in multiple generations of mice. Pregnant CD-1 mice were orally dosedwithcornoil (vehicle control) orDEHP(20 and 200mg/kg/d and 500 and 750mg/kg/d) fromgestational day 11 until birth. The F1 females were mated with untreated males to create the F2 generation, and the F2 females were mated with untreated males to create the F3 generation. At 1 year, ovaries, hormones, and estrous cycles were analyzed in each generation. Prenatal DEHP exposure altered estrous cyclicity (750mg/kg/d), increased the presence of ovarian cysts (750mg/kg/d), and decreased total follicle numbers (750 mg/kg/d) in the F1 generation. It also decreased anogenital distance (200mg/kg/d) and altered follicle numbers (200mg/kg/d and 500 mg/kg/d) in the F2 generation, and it altered estrous cyclicity (20 and 200 mg/kg/d and 500 and 750 mg/kg/d) and decreased folliculogenesis (200 mg/kg/d and 500 mg/kg/d) in the F3 generation. Further, prenatal DEHP increased estradiol levels (F1 and F3), decreased testosterone levels (F1, F2, and F3), decreased progesterone levels (F2), altered gonadotropin hormone levels (F1 and F3), and decreased inhibin B levels (F1 and F3). Collectively, these data show that prenatal exposure to DEHP has multigenerational and transgenerational effects on female reproduction and it may accelerate reproductive aging.
AB - Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer in many consumer products. Although DEHP is a known endocrine disruptor, little is known about the effects of DEHP exposure on female reproduction. Thus, this study tested the hypothesis that prenatal DEHP exposure affects follicle numbers, estrous cyclicity, and hormone levels in multiple generations of mice. Pregnant CD-1 mice were orally dosedwithcornoil (vehicle control) orDEHP(20 and 200mg/kg/d and 500 and 750mg/kg/d) fromgestational day 11 until birth. The F1 females were mated with untreated males to create the F2 generation, and the F2 females were mated with untreated males to create the F3 generation. At 1 year, ovaries, hormones, and estrous cycles were analyzed in each generation. Prenatal DEHP exposure altered estrous cyclicity (750mg/kg/d), increased the presence of ovarian cysts (750mg/kg/d), and decreased total follicle numbers (750 mg/kg/d) in the F1 generation. It also decreased anogenital distance (200mg/kg/d) and altered follicle numbers (200mg/kg/d and 500 mg/kg/d) in the F2 generation, and it altered estrous cyclicity (20 and 200 mg/kg/d and 500 and 750 mg/kg/d) and decreased folliculogenesis (200 mg/kg/d and 500 mg/kg/d) in the F3 generation. Further, prenatal DEHP increased estradiol levels (F1 and F3), decreased testosterone levels (F1, F2, and F3), decreased progesterone levels (F2), altered gonadotropin hormone levels (F1 and F3), and decreased inhibin B levels (F1 and F3). Collectively, these data show that prenatal exposure to DEHP has multigenerational and transgenerational effects on female reproduction and it may accelerate reproductive aging.
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U2 - 10.1210/en.2017-03004
DO - 10.1210/en.2017-03004
M3 - Article
C2 - 29228129
AN - SCOPUS:85045924914
SN - 0013-7227
VL - 159
SP - 795
EP - 809
JO - Endocrinology
JF - Endocrinology
IS - 2
ER -