Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Abstract

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.

Hemopexin and α1-microglobulin heme scavengers with differential involvement in preeclampsia and fetal growth restriction

“…Additionally, we show that fetuses from PE pregnancies without FGR did not present any difference compared to controls. These findings were independent of fetal sex in line with previous reports on comparable free HbF levels among male and female fetuses [37,38].…”

Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas

“…The following are available online at , Figure S1: Negative controls for antibodies and in situ hybridization probes, Figure S2: In situ analysis of alpha- and gamma-globin mRNAs in placenta stroma, Figure S3: Semi-quantification of the images from immunostaining analyses using ImageJ, Table S1: Detailed description of clinical characteristics of the patients for each set of experiments [ 73 ].…”

Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

“…There is a lack of evidence regarding a molecular basis for the association between fetal sex and PE. Our previous study showed that CD99 mRNA was upregulated in umbilical cord blood erythroid cells from male fetuses in PE pregnancies [16], and we speculated that CD99 expression, regulated by the SNP rs311103 genotype, might play a role in the pathogenesis of PE in a fetal sex-dependent fashion.…”

“…The obstetric outcomes are determined by complex interactions between the mother, the placenta and the fetus in a fetal sex-dependent fashion [15]; the exact mechanisms, however, are not known. Recent transcriptome findings by Masoumi et al gave an indication that CD99 expression is upregulated in umbilical cord blood erythroid cells in male fetuses from PE pregnancies [16].…”