Alterations in the Maternal Peripheral Microvascular Response in Pregnancies Complicated by Preeclampsia and the Impact of Fetal Sex

Abstract Context Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. Sexually dimorphic signaling at early stages of placentation are not defined. Objective Investigate the impact of fetal sex on maternal-fetal crosstalk. Design Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq). Setting Academic institution. Samples Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies. Main outcome measures Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins. Results We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population. Conclusions Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.

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Does Fetal Sex Influence the Risk of Preterm Delivery in Dichorionic Twin Pregnancies After Spontaneous Conception?

Twin Research and Human Genetics ◽

10.1375/twin.13.5.495 ◽

2010 ◽

Vol 13 (5) ◽

pp. 495-500 ◽

Cited By ~ 6

Author(s):

Katharina Klein ◽

Christof Worda ◽

Maria Stammler-Safar ◽

Peter Husslein ◽

Norbert Gleicher ◽

...

Keyword(s):

Body Mass Index ◽

Preterm Delivery ◽

Body Mass ◽

Maternal Age ◽

Maternal Body Mass Index ◽

Fetal Sex ◽

Spontaneous Conception ◽

Spontaneous Preterm Delivery ◽

The Impact ◽

Twin Pregnancies

Objective: The incidence of preterm delivery has been increasing, and our aim was to estimate the influence of fetal sex on the risk of preterm delivery in dichorionic twins after spontaneous conception.Methods: 125 spontaneously conceived dichorionic twin gestations, with viable fetuses, born after 24 weeks and delivered spontaneously before 37 weeks, were enrolled. The impact of fetal sex, previous preterm delivery, maternal age, body-mass-index, smoking, and parity on gestational age at birth were evaluated.Results: Despite similar baseline characteristics in all three groups, women with one or two male fetuses delivered significantly more often before 34 weeks than patients with two female fetuses, 48% (23/48) and 43% (19/44) vs 21% (7/33),p= .04. Regression analyses, including fetal sex, maternal age, maternal body-mass-index, smoking, previous preterm delivery and parity, revealed that only fetal sex was significantly associated with spontaneous preterm delivery (p= .03).Conclusion: Fetal sex appears to be a risk factor for preterm delivery in spontaneously conceived dichorionic twin gestations. Twin pregnancies with one or two male fetuses seem to be at higher risk for spontaneous preterm delivery than those with only females.

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570: What is the impact of fetal sex on maternal glucose metabolism?

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2015.10.615 ◽

2016 ◽

Vol 214 (1) ◽

pp. S307

Author(s):

Edward H. Springel ◽

Erica K. Berggren ◽

Larraine Huston-Presley ◽

Patrick M. Catalano

Keyword(s):

Glucose Metabolism ◽

Fetal Sex ◽

The Impact ◽

Maternal Glucose

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110: The impact of fetal sex on pregnancy outcome in twin pregnancies – who is to blame?

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2009.10.125 ◽

2009 ◽

Vol 201 (6) ◽

pp. S56

Author(s):

Nir Melamed ◽

Yariv Yogev ◽

Marek Glezerman

Keyword(s):

Pregnancy Outcome ◽

Fetal Sex ◽

The Impact ◽

Twin Pregnancies

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Effect of Prenatal Vitamin D Supplementation on Placental Angiogenic Factors in Bangladesh (FS08-07-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.fs08-07-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Anita Subramanian ◽

Casey Carr ◽

Eszter Papp ◽

Kellie Murphy ◽

Abdullah Al Mahmud ◽

...

Keyword(s):

Vitamin D ◽

Growth Factor ◽

Controlled Trial ◽

Secondary Analysis ◽

Vitamin D Supplementation ◽

Angiogenic Factors ◽

Fetal Sex ◽

Maternal Vitamin ◽

The Mean ◽

The Impact

Abstract Objectives To determine the effect of prenatal vitamin D supplementation on expression of angiogenic factors in the placenta. Methods This is a secondary analysis of the Maternal Vitamin D for Infant Growth trial, a randomized controlled trial of maternal vitamin D supplementation in Dhaka, Bangladesh. We examined the expression of angiogenic factors in placental tissues. Women (n = 1300) were enrolled at 17–24 weeks gestation and randomized to receive: placebo, 4200 IU/week, 16,800 IU/week or 28,000 IU/week until delivery. We examined a subset of randomly selected placentas (n = 80) collected at birth, which included 20 tissues (10 male & 10 female offspring) from each treatment group in maternal/fetal pairs. A full thickness placental core was collected; fixed in formalin and embedded in paraffin. Tissue sections were stained for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) using immunofluorescence. ImageJ was used to quantify intensity and % area of expression. T-tests were used to estimate the effects of each vitamin D dose on expression of angiogenic factors, compared to placebo. Interactions by fetal sex were also examined. Results The mean (SD) for % area of expression was 17.0 (4.0) for VEGF and 14.8 (1.9) for PlGF. The mean (SD) for intensity was 6520 (1549) for VEGF and 5716 (734) for PlGF. There were no significant differences in VEGF and PlGF between any vitamin D treatment groups versus placebo for % area or intensity of expression (Table 1). The effect of vitamin D treatment was not modified by fetal sex. Conclusions Vitamin D supplementation starting from mid-pregnancy until delivery did not effect expression of two key angiogenic factors in the placenta at term. The impact of periconception vitamin D supplementation on expression of angiogenic factors in the placenta remains unknown. Funding Sources Bill and Melinda Gates Foundation. Supporting Tables, Images and/or Graphs

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