title: Does paternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affect the sex ratio of offspring?
abstract: In 1976, men who were exposed to the highest concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after an explosion at a chemical plant near Seveso, Italy, produced more girls than boys. However, few studies have examined the possibility that the exposure of laboratory animals to TCDD, especially that of males, could lead to a lower male/female sex ratio. The aim of this study was to investigate whether direct paternal exposure to TCDD affects the sex ratio of offspring using a relatively large-scale experimental design. Male ICR mice (n=120) were randomly assigned to three, one of which served as a vehicle control, the other two were administered TCDD orally with an initial loading dose of 2 or 2,000 ng TCDD/kg, followed by a weekly maintenance dose of 0.4 (T2/0.4 group) or 400 (T2000/400 group) ng/kg prior to mating. The major organs of each mouse were weighed and histopathologically and immunohistologically investigated, and the sex ratio of offspring [males/(males + females) x 100] was calculated in each dam. There were no significant effects on organ weights, or on the structure of the testis and epididymis between the control and TCDD-exposed males, but TCDD administration produced a significantly lower proportion of male offspring from T2000/400-exposed sires despite no alteration in litter size (
  
  
  METHODS
  53.1 +/- 1.7; T2/0.4: 48.8 +/- 2.5; T2000/400: 46.2 +/- 2.1). In addition, we further divided the T2000/400 group into 3 subgroups based on the proportion of CYP1A1-immunoreactive areas in the liver; there was a significant correlation between sex ratio and CYP1A1 immunoreactivity. Thus, the present study confirms that direct paternal exposure to TCDD might be associated with an alteration in the sex ratio of offspring. Possible mechanisms through which TCDD might decrease the fertility potential of Y-bearing gametes before conception are discussed.
authors.affiliation: Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Ishihara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Warita
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanida
authors.forename: Teruo
authors.initials: T
authors.lastname: Sugawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004822:Epididymis / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018812:Paternal Exposure; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D011897:Random Allocation; D012744:Sex Ratio; D013737:Testis / Q000473:pathology
chemical_list: D052244:Endocrine Disruptors; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1