Embryonic loss due to exposure to polycyclic aromatic hydrocarbons is mediated by Bax.
The high miscarriage rates observed in women smokers raises the possibility that chemicals in cigarette smoke could be detrimental to embryo development. Previous studies have established that polycyclic aromatic hydrocarbons (PAHs), transactivate the arylhydrocarbon receptor (AhR), leading to cell death. Herein we show that PAH exposure results in murine embryo cell death, acting as a potential mechanism underlying cigarette-smoking-induced pregnancy loss. Cell death was preceded by increases in Bax levels, activation of caspase-3 and decreased litter size. Chronic exposure of females to PAHs prior to conception impaired development, resulting in a higher number of resorptions. This embryonic loss could not be prevented by the disruption of Hrk, but was diminished in embryos lacking Bax. We conclude that exposure of early embryos to PAHs reduces the allocation of cells to the embryonic and placental lineages by inducing apoptosis in a Bax-dependent manner, thus compromising the developmental potential of exposed embryos.
Detmar
Jacqui
J
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Rabaglino
Tatiana
T
Taniuchi
Yoshinari
Y
Oh
Jaymin
J
Acton
Beth M
BM
Benito
Adalberto
A
Nunez
Gabriel
G
Jurisicova
Andrea
A
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D001755:Blastocyst / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D006801:Humans; D008098:Litter Size / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009479:Neuropeptides / Q000502:physiology; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D012907:Smoking / Q000009:adverse effects; D051028:bcl-2-Associated X Protein / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C494827:Bax protein, mouse; C107631:Hrk protein, mouse; D009479:Neuropeptides; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; D053148:Caspase 3