BIO 313 Embryology Lecture #37 Germ Line & Birth Defects

BIO 313 EmbryologyLecture #37Germ Line & Birth Defects Embryonic Neuronal (red) and Glial Cells (green) Dr. Karen SchmeichelApril 25, 2008

Lit Review/Lab Reports/Lab Notebooks • Presentation Rubric • Thank you cards • Review Sheet • Final Exam next Monday 4/28 • Brunch on 5/5 8AM? Business:

Briefly consider germ line biology • - how are haploid germ cells specified? • Teratogens • - Sensitive stages in human development • - Environmental exposures and • birth defects • -Medical drugs • -Alcohol • - Extrogen Disruptors Objectives:

Germ line precursors are established very early in development Mammalian Oocyte in follicle Mouse Seminiferous Tubule

Fig.19.2 Inhibition of transcription in germ cell precursors of C. elegans – epigenetic regulation

Fig. 19.3 The pole plasm of Drosophila

Fig.19.16 Migration of primordial germ cells in the chick embryo

Fig.19.11 Migration of germ cells in the Drosophila embryo:attractive and repulsive forces at play

Embryonic Neuronal (red) and Glial Cells (green)

Pesticides damage animal’s embryos:Are humans immune?

1962The “Thalidomide Babies”Carson: “Thalidomide and pesticides… represent our willingness to rush ahead and use something without knowing what the results will be.”

Fig. 21.10 Periods and degrees of sensitivity of embryonic organs to teratogens Nervous system is always a target, organ systems susceptible from wk 3-8

Fig. 21.11 Comparison of a brain from an infant with Fetal Alcohol Syndrome with a brain from a normal infant of the same age

21.12 Alcohol-induced cell death in 9d mouse embryos No EtOH + EtOH + EtOH + Superoxide inhibitor

Fig. 21.12 7 mM EtOH (1 drink) causes reduced L1-mediated cell adhesion

Retinoic Acid (oxidized Vitamin A)

Fig. 21.13 DES is an “environmental estrogen”: endocrine disruptors

Fig. 21.13 Hox gene expression governs female reproductive tract organization

Fig. 21.14 In situ hybridization of a Hoxa10probe shows that DES exposure represses Hoxa10

Bisphenol A (BPA) is an estrogen mimetic used in plastics and to line aluminum cans

Fig. 21.16 Bisphenol A causes meiotic defects in maturing oocytes

Yes, there is a reason for concern here, but let’s not get hysterical! • It is good to be aware of human tendencies towards trying the latest technique/procedure: be informed! • Good news is added regulation through FDA etc. • -- (CDC’s National Center for Birth Defects and Developmental Disabilities: • http://www.cdc.gov/ncbddd/) • Remember to query the experimental model: mice have different metabolism than humans & and teratogen studies on cells in culture do not factor in drug modification and clearance. Summary

What Do Cells in the Human Breast Look Like? Luminal Epithelial Cells: Cells that give rise to tumors

Human Breast Cells in Culture Acinus in Tissue Explant Cultured Breast Cells Do these cultured cells look anything like breast cells? Does it matter?

Yes, It Does! Breast Tissue Explant Monolayer Culture Protein-rich Tissue Matrix 3-Dimensional Culture

Human Breast Cells in Culture Cultured Breast Cells Acinus in Tissue Explant Br. Cells in 3D Petersen et al. 1992 PNAS 89:9064

3-D Cultures Can Distinguish Normal vs Cancer Normal Breast Breast Tumor

Breast Cancer “Reversion” in 3D Cultures Cancer + Drug Normal Cancer Cytoskel. Nuclei Cell Junctions Weaver et al. 1997 JCB 137:231

AZU-1 Re-expression Induces Reversion in Breast Cancer Cells Cancer + AZU-1 gene Normal Cancer A B C

BIO 313 Embryology Lecture #37 Germ Line & Birth Defects