Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes.
OBJECTIVE
To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies.


METHODS
Prospective study.


METHODS
University women's clinic and academic research laboratory.


METHODS
Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.


METHODS
Placenta and placenta bed biopsies were collected after delivery.


METHODS
Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry.


RESULTS
Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha2 and gamma transcripts were significantly overexpressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains.


CONCLUSIONS
We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation.
Centlow
Magnus
M
Department of Obstetrics and Gynecology, Lund University, Lund, Sweden. magnus.centlow@med.lu.se
Carninci
Piero
P
Nemeth
Krisztian
K
Mezey
Eva
E
Brownstein
Michael
M
Hansson
Stefan R
SR
D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015723:Gene Library; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000098:blood supply* / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D006454:Hemoglobins; D012333:RNA, Messenger