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Article ; Online: Extracellular Vesicles in Preeclampsia: Can Small Packages Carry a Big Punch?

Hess, Philip E / Winn, Virginia D

2022 Volume 134, Issue 4, Page(s) 710–712

MeSH term(s)	Cardiovascular Physiological Phenomena ; Extracellular Vesicles ; Female ; Humans ; Placenta/physiopathology ; Pre-Eclampsia/diagnosis ; Pre-Eclampsia/physiopathology ; Pregnancy
Language	English
Publishing date	2022-04-22
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80032-6
ISSN	1526-7598 ; 0003-2999
ISSN (online)	1526-7598
ISSN	0003-2999
DOI	10.1213/ANE.0000000000005898
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Article ; Online: Cell-Free Nucleic Acids for Early Prediction of Preeclampsia.

Moufarrej, Mira N / Winn, Virginia D / Quake, Stephen R

Current hypertension reports

2023 Volume 26, Issue 4, Page(s) 175–182

Abstract: Purpose of review: This review summarizes the potential of cell-free nucleic acids for predicting preeclampsia, contrasts them with other methods, and discusses these findings' relevance to preeclampsia's pathogenesis and care.: Recent findings: ... ...

Abstract	Purpose of review: This review summarizes the potential of cell-free nucleic acids for predicting preeclampsia, contrasts them with other methods, and discusses these findings' relevance to preeclampsia's pathogenesis and care. Recent findings: Recent studies have demonstrated the utility of cell-free nucleic acids in early preeclampsia risk prediction. Encouragingly, nucleic acid measurement exhibits similar or better sensitivity as compared to standard screening assays and furthermore sheds light on preeclampsia's underlying placental biology. Over the past decade, liquid biopsies measuring cell-free nucleic acids have found diverse applications, including in prenatal care. Recent advances have extended their utility to predict preeclampsia, a major cause of maternal mortality. These assays assess methylation patterns in cell-free DNA (cfDNA) or gene levels in cell-free RNA (cfRNA). Currently, preeclampsia care focuses on blood pressure control, seizure prevention, and delivery. If validated, early prediction of preeclampsia through liquid biopsies can improve maternal health and deepen our understanding of its causes.
MeSH term(s)	Pregnancy ; Humans ; Female ; Cell-Free Nucleic Acids/genetics ; Pre-Eclampsia ; Placenta ; Hypertension ; Blood Pressure
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2023-12-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-023-01291-z
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Article ; Online: Solving the Puzzle of Preterm Birth.

Stevenson, David K / Winn, Virginia D / Shaw, Gary M / England, Sarah K / Wong, Ronald J

Clinics in perinatology

2024 Volume 51, Issue 2, Page(s) 291–300

Abstract: Solving the puzzle of preterm birth has been challenging and will require novel integrative solutions as preterm birth likely arises from many etiologies. It has been demonstrated that many sociodemographic and psychological determinants of preterm birth ...

Abstract	Solving the puzzle of preterm birth has been challenging and will require novel integrative solutions as preterm birth likely arises from many etiologies. It has been demonstrated that many sociodemographic and psychological determinants of preterm birth relate to its complex biology. It is this understanding that has enabled the development of a novel preventative strategy, which integrates the omics profile (genome, epigenome, transcriptome, proteome, metabolome, microbiome) with sociodemographic, environmental, and psychological determinants of individual pregnant people to solve the puzzle of preterm birth.
MeSH term(s)	Humans ; Premature Birth/epidemiology ; Female ; Pregnancy ; Infant, Newborn ; Risk Factors
Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	193116-7
ISSN	1557-9840 ; 0095-5108
ISSN (online)	1557-9840
ISSN	0095-5108
DOI	10.1016/j.clp.2024.02.001
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Article ; Online: A Letter to President Biden and Secretary Designate of HHS Xavier Becerra: Remove Barriers to Federal Funding of Human Embryo and Fetal Tissue Research.

Santoro, Nanette / Caplan, Arthur / Strauss, Jerome / Winn, Virginia D

Reproductive sciences (Thousand Oaks, Calif.)

2021 Volume 28, Issue 4, Page(s) 933–935

Abstract: Human fetal tissue (HFT) has been used in biomedical research for nearly a century and has led to extraordinarily valuable discoveries that have benefitted humankind. Politicization of the use of HFT over recent years has led to the creation of numerous ... ...

Abstract	Human fetal tissue (HFT) has been used in biomedical research for nearly a century and has led to extraordinarily valuable discoveries that have benefitted humankind. Politicization of the use of HFT over recent years has led to the creation of numerous obstacles to scientific progress in this field. In July 2019, the imposition of redundant ethics policies was supplemented with the creation of the Human Fetal Tissue Ethics Advisory Board, which withheld funding of 13 out of 14 NIH grants that were favorably peer reviewed in the Summer of 2020. We believe that these new sets of restrictions are harmful to the goals of scientific progress and call upon the new administration of our government to allow peer review, not politics, to determine scientific merit and to reinstitute the previously existing ethics policies that were more than adequate to assure the appropriateness of human fetal tissue research.
MeSH term(s)	Biomedical Research ; Federal Government ; Fetal Research ; Fetus ; Humans ; United States
Language	English
Publishing date	2021-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2276411-2
ISSN	1933-7205 ; 1933-7191
ISSN (online)	1933-7205
ISSN	1933-7191
DOI	10.1007/s43032-021-00491-9
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Article ; Online: Corrigendum: Advances and potential of omics studies for understanding the development of food allergy.

Sindher, Sayantani B / Chin, Andrew R / Aghaeepour, Nima / Prince, Lawrence / Maecker, Holden / Shaw, Gary M / Stevenson, David / Nadeau, Kari C / Snyder, Michael / Khatri, Purvesh / Boyd, Scott D / Winn, Virginia D / Angst, Martin S / Chinthrajah, R Sharon

Frontiers in allergy

2024 Volume 5, Page(s) 1373485

Abstract: This corrects the article DOI: 10.3389/falgy.2023.1149008.]. ...

Abstract	[This corrects the article DOI: 10.3389/falgy.2023.1149008.].
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Published Erratum
ISSN	2673-6101
ISSN (online)	2673-6101
DOI	10.3389/falgy.2024.1373485
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Article ; Online: Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.

Miller, Hayley E / Tierney, Seda / Stefanick, Marcia L / Mayo, Jonathan A / Sedan, Oshra / Rosas, Lisa G / Melbye, Mads / Boyd, Heather A / Stevenson, David K / Shaw, Gary M / Winn, Virginia D / Hlatky, Mark A

American heart journal

2024 Volume 272, Page(s) 96–105

Abstract: Background: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the ... ...

Abstract	Background: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. Methods: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. Results: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). Conclusion: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.
MeSH term(s)	Humans ; Female ; Pregnancy ; Adult ; Carotid Intima-Media Thickness ; Hypertension, Pregnancy-Induced/physiopathology ; Hypertension, Pregnancy-Induced/epidemiology ; Vascular Stiffness/physiology ; Blood Pressure/physiology ; Risk Factors ; Atherosclerosis/physiopathology ; Atherosclerosis/epidemiology ; Atherosclerosis/diagnosis ; Atherosclerosis/complications ; Pulse Wave Analysis ; Carotid Arteries/diagnostic imaging ; Carotid Arteries/physiopathology ; Pre-Eclampsia/physiopathology ; Pre-Eclampsia/epidemiology ; Pre-Eclampsia/diagnosis ; Case-Control Studies ; Endothelium, Vascular/physiopathology
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80026-0
ISSN	1097-6744 ; 0002-8703
ISSN (online)	1097-6744
ISSN	0002-8703
DOI	10.1016/j.ahj.2024.03.004
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Article ; Online: Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers.

Sotiros, Alexandra / Thornhill, Dianne / Post, Miriam D / Winn, Virginia D / Armstrong, Jennifer

PloS one

2021 Volume 16, Issue 11, Page(s) e0260094

Abstract: Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and ... ...

Abstract	Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16-2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985-1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.
MeSH term(s)	Adult ; Female ; Fetal Blood/immunology ; Fetal Development ; Gestational Age ; Humans ; Infant, Newborn ; Interleukin-6/metabolism ; Maternal Age ; Middle Aged ; Placenta/immunology ; Placenta/pathology ; Pre-Eclampsia/immunology ; Pregnancy ; Premature Birth/immunology ; Prospective Studies ; Up-Regulation ; Young Adult
Chemical Substances	IL6 protein, human ; Interleukin-6
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0260094
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Article ; Online: Association of preconception paternal health and adverse maternal outcomes among healthy mothers.

Murugappan, Gayathree / Li, Shufeng / Leonard, Stephanie A / Winn, Virginia D / Druzin, Maurice L / Eisenberg, Michael L

American journal of obstetrics & gynecology MFM

2021 Volume 3, Issue 5, Page(s) 100384

Abstract: Background: Maternal morbidity continues to be an issue of national and global concern. Paternal preconception health may play a significant role in pregnancy outcomes and has received less attention than maternal health.: Objective: This study aimed ...

Abstract	Background: Maternal morbidity continues to be an issue of national and global concern. Paternal preconception health may play a significant role in pregnancy outcomes and has received less attention than maternal health. Objective: This study aimed to examine the association between preconception paternal health and the risk for adverse maternal outcomes among healthy mothers. Study design: This was a retrospective analysis of live births from 2009 through 2016 to healthy women aged 20 to 45 years recorded in the IBM Marketscan research database. Infants were linked to paired mothers and fathers using family ID. Preconception paternal health was assessed using the number of metabolic syndrome component diagnoses and the most common individual chronic disease diagnoses (hypertension, diabetes mellitus, obesity, hyperlipidemia, chronic obstructive pulmonary disease, cancer, and depression). Women with metabolic syndrome components were excluded to avoid potential confounding of maternal and paternal factors. Adverse maternal outcomes that were assessed included (1) abnormal placentation including placenta accreta spectrum, placenta previa, and placental abruption; (2) preeclampsia with and without severe features including eclampsia; and (3) severe maternal morbidity, identified as any indicator from the Centers for Disease Control and Prevention Index of life-threatening complications at the time of delivery to 6 weeks postpartum. The trend between preconception paternal health and each maternal outcome was determined using the Cochran-Armitage Trend test. The independent association of paternal health with maternal outcomes was also determined using generalized estimating equations models, accounting for some mothers who contributed multiple births during the study period, and by adjusting for maternal age, paternal age, region of birth, year of birth, maternal smoking, and average number of outpatient visits per year. Results: Among 669,256 births to healthy mothers, there was a significant trend between all adverse maternal outcomes and worsening preconception paternal health defined either as the number of metabolic syndrome diagnoses or number of chronic disease diagnoses (P<.001; Cochran-Armitage Trend test). In the generalized estimating equations model, the odds for preeclampsia without severe features increased in a dose-dependent fashion and were 21% higher (95% confidence interval, 1.17-1.26) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for preeclampsia with severe features and eclampsia increased in a dose-dependent fashion and were 19% higher (95% confidence interval, 1.09-1.30) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for severe maternal morbidity were 9% higher (95% confidence interval, 1.002-1.19) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for abnormal placentation were similar between the groups (adjusted odds ratio, 0.96; 95% confidence interval, 0.89-1.03). Conclusion: Among healthy mothers, we report that preconception paternal health is significantly associated with increased odds of preeclampsia with and without severe features and weakly associated with increased odds of severe maternal morbidity. These findings suggest that paternally derived factors may play significant roles in the development of adverse maternal outcomes in healthy women with a low a priori risk of obstetrical complications.
MeSH term(s)	Fathers ; Female ; Humans ; Infant ; Male ; Mothers ; Placenta ; Pregnancy ; Pregnancy Outcome/epidemiology ; Retrospective Studies
Language	English
Publishing date	2021-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2589-9333
ISSN (online)	2589-9333
DOI	10.1016/j.ajogmf.2021.100384
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Article ; Online: Siglec-6 Signaling Uses Src Kinase Tyrosine Phosphorylation and SHP-2 Recruitment.

Stefanski, Adrianne L / Renecle, Michael D / Kramer, Anita / Sehgal, Shilpi / Narasimhan, Purnima / Rumer, Kristen K / Winn, Virginia D

Cells

2022 Volume 11, Issue 21

Abstract: Preeclampsia is a pregnancy-specific disorder involving placental abnormalities. Elevated placental Sialic acid immunoglobulin-like lectin (Siglec)-6 expression has been correlated with preeclampsia. Siglec-6 is a transmembrane receptor, expressed ... ...

Abstract	Preeclampsia is a pregnancy-specific disorder involving placental abnormalities. Elevated placental Sialic acid immunoglobulin-like lectin (Siglec)-6 expression has been correlated with preeclampsia. Siglec-6 is a transmembrane receptor, expressed predominantly by the trophoblast cells in the human placenta. It interacts with sialyl glycans such as sialyl-TN glycans as well as binds leptin. Siglec-6 overexpression has been shown to influence proliferation, apoptosis, and invasion in the trophoblast (BeWo) cell model. However, there is no direct evidence that Siglec-6 plays a role in preeclampsia pathogenesis and its signaling potential is still largely unexplored. Siglec-6 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an ITIM-like motif in its cytoplasmic tail suggesting a signaling function. Site-directed mutagenesis and transfection were employed to create a series of Siglec-6 expressing HTR-8/SVneo trophoblastic cell lines with mutations in specific functional residues to explore the signaling potential of Siglec-6. Co-immunoprecipitation and inhibitory assays were utilized to investigate the association of Src-kinases and SH-2 domain-containing phosphatases with Siglec-6. In this study, we show that Siglec-6 is phosphorylated at ITIM and ITIM-like domains by Src family kinases. Phosphorylation of both ITIM and ITIM-like motifs is essential for the recruitment of phosphatases like Src homology region 2 containing protein tyrosine phosphatase 2 (SHP-2), which has downstream signaling capabilities. These findings suggest Siglec-6 as a signaling molecule in human trophoblasts. Further investigation is warranted to determine which signaling pathways are activated downstream to SHP-2 recruitment and how overexpression of Siglec-6 in preeclamptic placentas impacts pathogenesis.
MeSH term(s)	Female ; Humans ; Pregnancy ; Amino Acid Motifs/genetics ; Amino Acid Sequence ; Phosphorylation ; Placenta/metabolism ; Pre-Eclampsia/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Sialic Acid Binding Immunoglobulin-like Lectins/metabolism ; src-Family Kinases/metabolism ; Tyrosine/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Lectins/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism
Chemical Substances	Protein Tyrosine Phosphatase, Non-Receptor Type 6 (EC 3.1.3.48) ; Sialic Acid Binding Immunoglobulin-like Lectins ; src-Family Kinases (EC 2.7.10.2) ; Tyrosine (42HK56048U) ; SIGLEC6 protein, human ; Antigens, Differentiation, Myelomonocytic ; Lectins ; PTPN11 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48)
Language	English
Publishing date	2022-10-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11213427
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Article ; Online: Implementation of a comprehensive fertility biobanking initiative.

Wignarajah, Anjali / Alvero, Ruben / Lathi, Ruth B / Aghajanova, Lusine / Eisenberg, Michael / Winn, Virginia D / Behr, Barry / Murugappan, Gayathree

F&S science

2022 Volume 3, Issue 3, Page(s) 228–236

Abstract: Objective: To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment.: Design: Technical description article.: Setting: Academic ... ...

Abstract	Objective: To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment. Design: Technical description article. Setting: Academic fertility center. Patient(s): Fertility patients >18 years of age. Intervention(s): Enroll the patients interested in research in biobanking protocols. Main outcome measure(s): Patient recruitment and sample inventory from September 2020 to September 2021. Result(s): A total of 253 patients have enrolled in the Stanford Fertility and Reproductive Health biobanking initiatives since September 2020. The current inventory consists of 1,176 samples, including serums, plasmas, buffy coats, endometria, maternal deciduae, miscarriage chorionic villi, and human embryos (zygote, cleavage, and blastocyst stages). Conclusion(s): This biobanking initiative addresses a critical, unmet need in reproductive health research to make it possible for patients to donate excess embryos and gametes and preserves, for future research, valuable somatic and reproductive tissues that would otherwise be discarded. We present the framework of this biobanking initiative in order to support future efforts of establishing similar biorepositories.
MeSH term(s)	Abortion, Spontaneous ; Biological Specimen Banks ; Blastocyst ; Female ; Fertility ; Humans ; Pregnancy ; Zygote
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article
ISSN	2666-335X
ISSN (online)	2666-335X
DOI	10.1016/j.xfss.2022.01.001
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