title: Prenatal exposure to dexamethasone disturbs sex-determining gene expression and fetal testosterone production in male embryos.
abstract: Prenatal stress is known to cause intrauterine fetal growth retardation, and is also associated with various long-term effects in the form of metabolic and neurodevelopmental diseases in adults. Many of the diseases associated with prenatal stress exhibit a sex bias. Perturbations and vulnerability to prenatal stress are often more profound in males, but the mechanisms responsible for this relationship are not clear. We have previously shown that administration of the synthetic glucocorticoid, dexamethasone (Dex), at embryonic days 7.5, 8.5, and 9.5, induces embryonic growth restriction in a sex-dependent manner in a mouse model. Here we examined the effect of prenatal exposure to Dex on gonadal development. During male gonadal development, sex-determining genes, such as Sry, Sox9, and other downstream genes, were found to be dysregulated in response to prenatal Dex, whereas the genes for the ovarian pathway were affected to a lesser degree in females. In addition, fetal testosterone concentrations were decreased by prenatal exposure to Dex, in parallel with reduced numbers of 3β-hydroxysteroid dehydrogenase (3β-HSD)-positive cells in the embryonic testis. These results show that prenatal exposure to Dex differentially influences male versus female on the gene expression and hormone production during sex determination. We believe these studies provide valuable insights into possible mechanisms responsible for sex-specific responses to prenatal stress.
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: yshjyoon@hotmail.com.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: jylee517@yuhs.ac.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: mhkim1@yuhs.ac.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000506:poisoning; D003907:Dexamethasone / Q000506:poisoning*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000503:physiopathology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D000893:Anti-Inflammatory Agents; D013739:Testosterone; D003907:Dexamethasone
keywords: Dexamethasone; Glucocorticoid; Prenatal stress; Sex-determining genes; Testosterone