Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice

Lyda Yuliana Parra-Forero, Arlet Veloz-Contreras, Shirley Vargas-Marín, María Angelica Mojica-Villegas, Elim Alfaro-Pedraza, Mayrut Urióstegui-Acosta, Isabel Hernández-Ochoa

Research output: Contribution to journalArticle

Abstract

Because di(2-ethylhexyl) phthalate (DEHP) toxicity on ovarian function is incomplete, effects of DEHP oocyte fertilization and the resulting zygotes were investigated. Further, an analysis characterizing the stage of zygote arrest was performed. Female CD1 mice were dosed orally with DEHP (0, 20, 200 and 2000 μg/kg/day) for 30 days. Following an in vivo mating post-dosing, DEHP-treated females exhibited fewer oocytes/zygotes, fewer oocytes displaying the polar body extrusion, fewer 1-cell zygotes having 2-pronuclei, more unfertilized oocytes, and decreased number of zygotes at every stage of development. DEHP induced blastomere fragmentation in zygotes. DNA replication in zygotes directly assessed by the 5-Ethynyl-2′-deoxyuridine (5-EdU) incorporation assay and indirectly by dosing mice with 5-fluorouracil (5-FU) suggested that DEHP inhibits DNA replication. Our data suggest that DEHP at doses found in ‘every-day’ (200 μg/Kg/day) or occupational (2000 μg/Kg/day) environments induces zygote fragmentation and arrests its development from the 2-cell stage potentially impairing DNA replication.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalReproductive Toxicology
Volume90
DOIs
StatePublished - Dec 2019

Fingerprint

Zygote
Oocytes
Young Adult
DNA Replication
DNA
Polar Bodies
Blastomeres
phthalic acid
Fluorouracil
Extrusion
Toxicity
Fertilization
Assays

Keywords

  • DEHP
  • In vivo fertilization
  • Oocyte
  • Zygote
  • Zygote fragmentation

Cite this

Parra-Forero, L. Y., Veloz-Contreras, A., Vargas-Marín, S., Mojica-Villegas, M. A., Alfaro-Pedraza, E., Urióstegui-Acosta, M., & Hernández-Ochoa, I. (2019). Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice. Reproductive Toxicology, 90, 53-61. https://doi.org/10.1016/j.reprotox.2019.08.012
Parra-Forero, Lyda Yuliana ; Veloz-Contreras, Arlet ; Vargas-Marín, Shirley ; Mojica-Villegas, María Angelica ; Alfaro-Pedraza, Elim ; Urióstegui-Acosta, Mayrut ; Hernández-Ochoa, Isabel. / Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice. In: Reproductive Toxicology. 2019 ; Vol. 90. pp. 53-61.
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abstract = "Because di(2-ethylhexyl) phthalate (DEHP) toxicity on ovarian function is incomplete, effects of DEHP oocyte fertilization and the resulting zygotes were investigated. Further, an analysis characterizing the stage of zygote arrest was performed. Female CD1 mice were dosed orally with DEHP (0, 20, 200 and 2000 μg/kg/day) for 30 days. Following an in vivo mating post-dosing, DEHP-treated females exhibited fewer oocytes/zygotes, fewer oocytes displaying the polar body extrusion, fewer 1-cell zygotes having 2-pronuclei, more unfertilized oocytes, and decreased number of zygotes at every stage of development. DEHP induced blastomere fragmentation in zygotes. DNA replication in zygotes directly assessed by the 5-Ethynyl-2′-deoxyuridine (5-EdU) incorporation assay and indirectly by dosing mice with 5-fluorouracil (5-FU) suggested that DEHP inhibits DNA replication. Our data suggest that DEHP at doses found in ‘every-day’ (200 μg/Kg/day) or occupational (2000 μg/Kg/day) environments induces zygote fragmentation and arrests its development from the 2-cell stage potentially impairing DNA replication.",
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Parra-Forero, LY, Veloz-Contreras, A, Vargas-Marín, S, Mojica-Villegas, MA, Alfaro-Pedraza, E, Urióstegui-Acosta, M & Hernández-Ochoa, I 2019, 'Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice', Reproductive Toxicology, vol. 90, pp. 53-61. https://doi.org/10.1016/j.reprotox.2019.08.012

Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice. / Parra-Forero, Lyda Yuliana; Veloz-Contreras, Arlet; Vargas-Marín, Shirley; Mojica-Villegas, María Angelica; Alfaro-Pedraza, Elim; Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel.

In: Reproductive Toxicology, Vol. 90, 12.2019, p. 53-61.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alterations in oocytes and early zygotes following oral exposure to di(2-ethylhexyl) phthalate in young adult female mice

AU - Parra-Forero, Lyda Yuliana

AU - Veloz-Contreras, Arlet

AU - Vargas-Marín, Shirley

AU - Mojica-Villegas, María Angelica

AU - Alfaro-Pedraza, Elim

AU - Urióstegui-Acosta, Mayrut

AU - Hernández-Ochoa, Isabel

PY - 2019/12

Y1 - 2019/12

N2 - Because di(2-ethylhexyl) phthalate (DEHP) toxicity on ovarian function is incomplete, effects of DEHP oocyte fertilization and the resulting zygotes were investigated. Further, an analysis characterizing the stage of zygote arrest was performed. Female CD1 mice were dosed orally with DEHP (0, 20, 200 and 2000 μg/kg/day) for 30 days. Following an in vivo mating post-dosing, DEHP-treated females exhibited fewer oocytes/zygotes, fewer oocytes displaying the polar body extrusion, fewer 1-cell zygotes having 2-pronuclei, more unfertilized oocytes, and decreased number of zygotes at every stage of development. DEHP induced blastomere fragmentation in zygotes. DNA replication in zygotes directly assessed by the 5-Ethynyl-2′-deoxyuridine (5-EdU) incorporation assay and indirectly by dosing mice with 5-fluorouracil (5-FU) suggested that DEHP inhibits DNA replication. Our data suggest that DEHP at doses found in ‘every-day’ (200 μg/Kg/day) or occupational (2000 μg/Kg/day) environments induces zygote fragmentation and arrests its development from the 2-cell stage potentially impairing DNA replication.

AB - Because di(2-ethylhexyl) phthalate (DEHP) toxicity on ovarian function is incomplete, effects of DEHP oocyte fertilization and the resulting zygotes were investigated. Further, an analysis characterizing the stage of zygote arrest was performed. Female CD1 mice were dosed orally with DEHP (0, 20, 200 and 2000 μg/kg/day) for 30 days. Following an in vivo mating post-dosing, DEHP-treated females exhibited fewer oocytes/zygotes, fewer oocytes displaying the polar body extrusion, fewer 1-cell zygotes having 2-pronuclei, more unfertilized oocytes, and decreased number of zygotes at every stage of development. DEHP induced blastomere fragmentation in zygotes. DNA replication in zygotes directly assessed by the 5-Ethynyl-2′-deoxyuridine (5-EdU) incorporation assay and indirectly by dosing mice with 5-fluorouracil (5-FU) suggested that DEHP inhibits DNA replication. Our data suggest that DEHP at doses found in ‘every-day’ (200 μg/Kg/day) or occupational (2000 μg/Kg/day) environments induces zygote fragmentation and arrests its development from the 2-cell stage potentially impairing DNA replication.

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KW - In vivo fertilization

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