title: Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model.
abstract: The theory of fetal origins of adult disease was first proposed in 1989, and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. Because mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation, and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis, leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood; however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle, and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility, with maternal smoke-exposed animals having smaller litters and also taking longer to conceive. In conclusion, our results demonstrate that in utero and lactational exposure to cigarette smoke can have long-lasting effects on the fertility of the next generation of females.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Camlin
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia Telomere Length Regulation Group, Children's Medical Research Institute, Westmead, New South Wales, Australia.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Sobinoff
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: Sutherland
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Beckett
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Jarnicki
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Vanders
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia School of Biological Sciences, University of Auckland, Auckland, New Zealand eileen.mclaughlin@newcastle.edu.au.
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holt
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility / Q000187:drug effects*; D018811:Maternal Exposure; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D012906:Smoke / Q000009:adverse effects*; D013084:Sperm-Ovum Interactions
chemical_list: D012906:Smoke
keywords: cigarette smoke; in utero; oocyte; ovary; subfertility