Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders.


OBJECTIVE
The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method.


METHODS
Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues.


METHODS
This study was performed at a university hospital laboratory.


METHODS
This study comprised 12 regularly cycling women and 12 PCOS patients.


METHODS
Dysregulated signaling pathways in PCOSE were identified as a gene set.


RESULTS
Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE.


CONCLUSIONS
Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.
Kim
Jin Yeong
JY
Department of Obstetrics andGynecology, Cheil General Hospital and Women's Healthcare Center, Kwangdong University College of Medicine, Seoul, Korea.
Song
Haengseok
H
Kim
Hyunjoo
H
Kang
Hee Jung
HJ
Jun
Jin Hyun
JH
Hong
Sung Ran
SR
Koong
Mi Kyoung
MK
Kim
In Sun
IS
D000328:Adult; D000728:Androgens / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004717:Endometrium / Q000473:pathology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D020869:Gene Expression Profiling; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic
D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone