UCI、出生前の一般的な汚染物質への曝露とマウス胎児の卵巣障害を関連付ける研究を実施(UCI study links prenatal exposure to common pollutant and ovary damage in mouse fetuses)


2022-09-17 カリフォルニア大学校アーバイン校(UCI)



妊娠中のベンゾ[a]ピレン曝露は、ミトコンドリアアポトーシス経路を通じてF1卵巣生殖細胞を破壊し、生存卵子の質を低下させる Gestational Benzo[a]pyrene Exposure Destroys F1 Ovarian Germ Cells Through Mitochondrial Apoptosis Pathway and Diminishes Surviving Oocyte Quality

Kelli F Malott, Kathleen Leon Parada, Melody Lee, Edward Swanson, Ulrike Luderer
Toxicological Sciences  Published:22 August 2022

A, Experimental design for gestational BaP exposure and assessment of F1 ovarian effects during 2 critical windows of ovarian development. B, Experimental design for in vitro BaP exposure and assessment of induction of mitochondrial apoptosis pathway. C, Experimental design for F1 gestational BaP exposure and assessment of F1-derived MII oocyte oxidative stress and developmental competence. All details of each exposure and endpoint are described in the Materials and Methods. Figure was created with the help of Biorender.com.


Polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BaP), are products of incomplete combustion. In female mouse embryos primordial germ cells proliferate before and after arriving at the gonadal ridge around embryonic (E) 10 and begin entering meiosis at E13.5. Now oocytes, they arrest in the first meiotic prophase beginning at E17.5. We previously reported dose-dependent depletion of ovarian follicles in female mice exposed to 2 or 10 mg/kg-day BaP E6.5–15.5. We hypothesized that embryonic ovaries are more sensitive to gestational BaP exposure during the mitotic developmental window, and that this exposure results in persistent oxidative stress in ovaries and oocytes of exposed F1 female offspring. We orally dosed timed-pregnant female mice with 0 or 2 mg/kg-day BaP in oil from E6.5–11.5 (mitotic window) or E12.5–17.5 (meiotic window). Cultured E13.5 ovaries were utilized to investigate the mechanism of BaP-induced germ cell death. We observed statistically significant follicle depletion and increased ovarian lipid peroxidation in F1 pubertal ovaries following BaP exposure during either prenatal window. Culture of E13.5 ovaries with BaP induced germ cell DNA damage and release of cytochrome c from the mitochondria in oocytes, confirming that BaP exposure induced apoptosis via the mitochondrial pathway. Mitochondrial membrane potential, oocyte lipid droplet (LD) volume, and mitochondrial-LD colocalization were decreased and mitochondrial superoxide levels were increased in the MII oocytes of F1 females exposed gestationally to BaP. Results demonstrate similar sensitivity to germ cell depletion and persistent oxidative stress in F1 ovaries and oocytes following gestational BaP exposure during mitotic or meiotic windows.