title: Environmental tobacco smoke exposure during intrauterine period promotes granulosa cell apoptosis: a prospective, randomized study.
abstract: OBJECTIVE
  To evaluate the intrauterine effect of cigarette smoke on cell death and DNA damage in follicular cells of fetal ovarian tissue.
  
  
  METHODS
  A prospective, randomized study was conducted with 25 female wistar-albino rats. The rats were randomized to be exposed either to cigarette smoke or to room air, initiating from proestrous period and during pregnancy. Newborn female rats were categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during intrauterine life and Group 2 (n = 7) that had been exposed to room air during intrauterine life. Bilateral ooferectomies were performed on the 2nd week of their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP-Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses with caspase-3 were used for detection of DNA damage and apoptosis. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary outcomes were ovarian follicle counts and birth weights of newborn rats.
  
  
  RESULTS
  There was a significant increase of HSCORE and apoptotic index in Group 1. Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method was observed in granulosa cells in Group 1.
  
  
  CONCLUSIONS
  Intrauterine exposure to cigarette smoke diminishes ovarian reserve of female offspring, raising the concern about the generational impact of maternal smoking on ovarian function in the human.
authors.affiliation: Department of Reproductive Endocrinology and IVF, Dr. Zekai Tahir Burak Women's Health, Education and Research Hospital, Cebeci, Ankara, Turkey.
authors.forename: Sevtap
authors.initials: S
authors.lastname: Kilic
authors.forename: Beril
authors.initials: B
authors.lastname: Yuksel
authors.forename: Nese
authors.initials: N
authors.lastname: Lortlar
authors.forename: Semra
authors.initials: S
authors.lastname: Sertyel
authors.forename: Tarik
authors.initials: T
authors.lastname: Aksu
authors.forename: Sertac
authors.initials: S
authors.lastname: Batioglu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D019570:Inhalation Exposure / Q000009:adverse effects*; D018811:Maternal Exposure / Q000009:adverse effects*; D006080:Ovarian Follicle / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D014028:Tobacco Smoke Pollution; D053148:Caspase 3