title: Investigation of sexual dimorphisms through mouse models and hormone/hormone-disruptor treatments.
abstract: Sexual dimorphism in mouse reproductive tissues is observable in adult, post-natal, and embryonic stages. The development of sexually dimorphic tissues starts with an ambisexual structure. It is followed by sex-specific organogenesis as guided by different signaling pathways that occur from late embryonic stages. The measurement of the anogenital distance (AGD), and the observation of the external genitalia are practical ways to distinguish male and female pups at birth and thereafter. Careful observation of the morphological or histological features and the molecular signatures of the external genitalia and perineum enable identification of sex or feminization/masculinization of embryos. Aberrations in hormone signaling via castration or treatment with hormones or hormone disruptors result in dysmorphogenesis of reproductive tissues. Several hormone disruptors have been used to modulate different aspects of hormone action through competitive inhibition and exogenous hormone treatment. Concomitantly, the vast advancement of conditional mutant mouse analysis leads to the frequent utilization of Cre recombination technology in the study of reproductive/urogenital tissue development. Mouse Cre-lines that are tissue-specific and cell-specific are also effective tools in identifying the molecular mechanisms during sexually dimorphic development. Cre-lines applicable to different cell populations in the prostate, seminal vesicles, testis and ovaries, and mammary glands are currently being utilized. In the external genitalia and perineum, Cre lines that examine the signaling pathways of cells of endodermal, ectodermal, and mesenchymal origin reveal the roles of these tissues in the development of the external genitalia. The interaction of hormones and growth factors can be examined further through a variety of techniques available for researchers. Such cumulative information about various technologies is summarized.
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan.
authors.forename: Lerrie Ann
authors.initials: LA
authors.lastname: Ipulan
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan.
authors.forename: Dennis
authors.initials: D
authors.lastname: Raga
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Murashima
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsumaru
authors.affiliation: Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Cunha
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, Japan. Electronic address: genyama77@yahoo.co.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005835:Genitalia / Q000196:embryology / Q000254:growth & development*; D006727:Hormone Antagonists / Q000008:administration & dosage; D006728:Hormones / Q000378:metabolism*; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics*; D012733:Sex Differentiation / Q000235:genetics*
chemical_list: D006727:Hormone Antagonists; D006728:Hormones; C045073:Cre recombinase; D019426:Integrases
keywords: Androgen; External genitalia; Hormone; Hormone disruption; Mouse Cre lines; Perineum; Reproductive tissue; Sexual dimorphism