TY - JOUR
T1 - Di(2-ethylhexyl) phthalate exposure during prenatal development causes adverse transgenerational effects on female fertility in mice
AU - Rattan, Saniya
AU - Brehm, Emily
AU - Gao, Liying
AU - Flaws, Jodi A.
N1 - National Institutes of Health (P01 ES022848 and T32 ES007326); Environmental Protection Agency (RD 83459301).
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant and endocrine disrupting chemical, but little is known about its effects on female reproduction. Thus, we tested the hypothesis that prenatal exposure to DEHP accelerates the onset of puberty, disrupts estrous cyclicity, disrupts birth outcomes, and reduces fertility in the F1, F2, and F3 generations of female mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 μg/kg/day and 500 and 750 mg/kg/day) from gestation day 10.5 until birth. F1 females were mated with untreated males to obtain the F2 generation. F2 females were mated with untreated males to produce the F3 generation. In all generations, the onset of puberty, estrous cyclicity, select birth outcomes, and fertility-related indices were evaluated. In the F1 generation, prenatal DEHP exposure (200 μg/kg/day) accelerated the onset of puberty, it (200 μg and 500 mg/kg/day) disrupted estrous cyclicity, and it (20 and 200 μg/kg/day) decreased fertility-related indices. In the F2 generation, ancestral DEHP exposure (500 mg/kg/day) accelerated the onset of puberty, it (20 and 200 μg/kg/day) disrupted estrous cyclicity, it (20 μg and 500 mg/kg/day) increased litter size, and it (500 mg/kg/day) decreased fertility-related indices. In the F3 generation, ancestral DEHP exposure (20, 200 μg, and 500 mg/kg/day) accelerated the onset of puberty, it (20 μg/kg/day) disrupted estrous cyclicity, and it (750 mg/kg/day) decreased female pup anogenital index. Collectively, these data indicate that prenatal DEHP exposure causes female reproductive problems in a multigenerational and transgenerational manner.
AB - Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant and endocrine disrupting chemical, but little is known about its effects on female reproduction. Thus, we tested the hypothesis that prenatal exposure to DEHP accelerates the onset of puberty, disrupts estrous cyclicity, disrupts birth outcomes, and reduces fertility in the F1, F2, and F3 generations of female mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 μg/kg/day and 500 and 750 mg/kg/day) from gestation day 10.5 until birth. F1 females were mated with untreated males to obtain the F2 generation. F2 females were mated with untreated males to produce the F3 generation. In all generations, the onset of puberty, estrous cyclicity, select birth outcomes, and fertility-related indices were evaluated. In the F1 generation, prenatal DEHP exposure (200 μg/kg/day) accelerated the onset of puberty, it (200 μg and 500 mg/kg/day) disrupted estrous cyclicity, and it (20 and 200 μg/kg/day) decreased fertility-related indices. In the F2 generation, ancestral DEHP exposure (500 mg/kg/day) accelerated the onset of puberty, it (20 and 200 μg/kg/day) disrupted estrous cyclicity, it (20 μg and 500 mg/kg/day) increased litter size, and it (500 mg/kg/day) decreased fertility-related indices. In the F3 generation, ancestral DEHP exposure (20, 200 μg, and 500 mg/kg/day) accelerated the onset of puberty, it (20 μg/kg/day) disrupted estrous cyclicity, and it (750 mg/kg/day) decreased female pup anogenital index. Collectively, these data indicate that prenatal DEHP exposure causes female reproductive problems in a multigenerational and transgenerational manner.
KW - DEHP
KW - Fertility
KW - Prenatal
KW - Transgenerational
UR - http://www.scopus.com/inward/record.url?scp=85048107942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048107942&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfy042
DO - 10.1093/toxsci/kfy042
M3 - Article
C2 - 29471507
AN - SCOPUS:85048107942
SN - 1096-6080
VL - 163
SP - 420
EP - 429
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 2
ER -