Developmental Diethylstilbestrol Exposure Alters Genetic Pathways of Uterine Cytodifferentiation

Autor: Jussi Vuoristo, John A. McLachlan, Wei-Wei Huang, Liang Ma, Tung-Chin Chiang, Neysa Garner, Yan Yin, Qun Bi
Rok vydání: 2005
Předmět:
Time Factors
Transcription
Genetic
Cellular differentiation
Apoptosis
Epithelium
Mice
Endocrinology
Pregnancy
In Situ Hybridization
Oligonucleotide Array Sequence Analysis
Mice
Knockout
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
General Medicine
Up-Regulation
Cell biology
DNA-Binding Proteins
Cell Transformation
Neoplastic
medicine.anatomical_structure
Prenatal Exposure Delayed Effects
Knockout mouse
Keratins
Female
medicine.medical_specialty
DNA
Complementary
Mice
Transgenic
Cell fate determination
Biology
Models
Biological
Wnt-5a Protein
Ribonucleases
Simple columnar epithelium
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Cell Lineage
Estrogens
Non-Steroidal
Diethylstilbestrol
Molecular Biology
Transcription factor
Cell Proliferation
DNA Primers
Homeodomain Proteins
Metaplasia
Uterus
Alkaline Phosphatase
Wnt Proteins
Gene expression profiling
WNT7A
Infertility
Mutation
Pregnancy
Animal
Zdroj: Molecular Endocrinology. 19:669-682
ISSN: 1944-9917
0888-8809
DOI: 10.1210/me.2004-0155
Popis: The formation of a simple columnar epithelium in the uterus is essential for implantation. Perturbation of this developmental process by exogenous estrogen, such as diethylstilbestrol (DES), results in uterine metaplasia that contributes to infertility. The cellular and molecular mechanism underlying this transformation event is not well understood. Here we use a combination of global gene expression analysis and a knockout mouse model to delineate genetic pathways affected by DES. Global gene expression profiling experiment revealed that neonatal DES treatment alters uterine cell fate, particularly in the luminal epithelium by inducing abnormal differentiation, characterized by the induction of stratified epithelial markers including members of the small proline-rich protein family and epidermal keratins. We show that Msx2, a homeodomain transcription factor, functions downstream of DES and is required for the proper expression of several genes in the uterine epithelium including Wnt7a, PLAP, and K2.16. Finally, Msx2−/− uteri were found to exhibit abnormal water trafficking upon DES exposure, demonstrating the importance of Msx2 in tissue responsiveness to estrogen exposure. Together, these results indicate that developmental exposure to DES can perturb normal uterine development by affecting genetic pathways governing uterine differentiation.
Databáze: OpenAIRE
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