Yoel Sadovsky

University of Pittsburgh

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D. Michael Nelson

University of South Carolina

Jean‐François Mouillet

Magee-Womens Research Institute

Yingshi Ouyang

University of Pittsburgh

Tianjiao Chu

Magee-Womens Research Institute

Samuel Parry

University of Pennsylvania

George R. Saade

The University of Texas Medical Branch at Galveston

Carolyn B. Coyne

Duke University

Michael W. Varner

Society for Maternal-Fetal Medicine

Joseph Biggio

Ochsner Medical Center

Radek Bukowski

The University of Texas at Austin

Cooperative Institutions

University of Pittsburgh

214

Washington University in St. Louis

149

Harvard University

126

Duke University

118

University of North Carolina at Chapel Hill

113

National Institutes of Health

104

Eunice Kennedy Shriver National Institute of Child Health and Human Development

103

University of California, San Francisco

101

Columbia University

101

University of Washington

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Utilization of Fetal Heart Rate Acceleration Following Vibroacoustic Stimulation in Labor to Predict Fetal Acidemia and Base Deficit Levels

The Journal of Maternal-Fetal & Neonatal Medicine (1995)

James Bartelsmeyer Yoel Sadovsky B. G. Fleming Roy H. Petrie

The absence of a fetal response to vibroacoustic stimulation (VAS) performed during labor may be an indicator of fetal acidemia. A lack of fetal heart rate (FHR) acceleration following VAS has been correlated with fetal scalp blood pH < 7.20. A measurement of pH alone cannot distinguish respiratory from metabolic acidosis. This study correlates the FHR response to VAS during labor with fetal scalp blood pH and base deficit levels. The mean pH and base deficit levels of patients not demonstrating FHR response were 7.24 and 5.90 mEq/L, respectively. A lack of FHR response after VAS was moderately sensitive to detect pH < 7.20 but more sensitive to detect pH < 7.10. A lack of FHR acceleration was moderately sensitive to detect base deficit > 7 mEq/L but was more sensitive to detect levels >10 mEq/L. All patients with pH < 7.20 and demonstrating FHR response after VAS had base deficit < 10 mEq/L. Forty-four percent of patients with pH < 7.20 and no FHR response after VAS had base deficit > 10 mEq/L. This study suggests that VAS during labor can predict fetal acidemia and differentiate between respiratory and metabolic acidosis.

Respiratory acidosis

Arterial pH

10.3109/14767059509017311

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Citations (1)

Microbial Vertical Transmission during Human Pregnancy

Cell Host & Microbe (2017)

Nitin Arora Yoel Sadovsky Terence S. Dermody Carolyn B. Coyne

Zika Virus

Transplacental

Rubella virus

10.1016/j.chom.2017.04.007

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Citations (342)

Perinatal Outcomes and Unconventional Natural Gas Operations in Southwest Pennsylvania

PLoS ONE (2015)

Shaina L. Stacy LuAnn L. Brink Jacob Larkin Yoel Sadovsky Bernard D. Goldstein

Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007–2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10–1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.

Quartile

10.1371/journal.pone.0126425

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Citations (136)

Internalization of trophoblastic small extracellular vesicles and detection of their miRNA cargo in P‐bodies

Journal of Extracellular Vesicles (2020)

Hui Li Itziar Pinilla‐Macua Yingshi Ouyang E Sadovsky Kazuhiro Kajiwara

ABSTRACT Pregnancy is a unique situation, in which placenta‐derived small extracellular vesicles (sEVs) may communicate with maternal and foetal tissues. While relevant to homoeostatic and pathological functions, the mechanisms underlying sEV entry and cargo handling in target cells remain largely unknown. Using fluorescently or luminescently labelled sEVs, derived from primary human placental trophoblasts or from a placental cell line, we interrogated the endocytic pathways used by these sEVs to enter relevant target cells, including the neighbouring primary placental fibroblasts and human uterine microvascular endothelial cells. We found that trophoblastic sEVs can enter target cells, where they retain biological activity. Importantly, using a broad series of pharmacological inhibitors and siRNA‐dependent silencing approaches, we showed that trophoblastic sEVs enter target cells using macropinocytosis and clathrin‐mediated endocytosis pathways, but not caveolin‐dependent endocytosis. Tracking their intracellular course, we localized the sEVs to early endosomes, late endosomes, and lysosomes. Finally, we used coimmunoprecipitation to demonstrate the association of the sEV microRNA (miRNA) with the P‐body proteins AGO2 and GW182. Together, our data systematically detail endocytic pathways used by placental sEVs to enter relevant fibroblastic and endothelial target cells, and provide support for “endocytic escape” of sEV miRNA to P‐bodies, a key site for cytoplasmic RNA regulation.

Internalization

Pinocytosis

Argonaute

P-bodies

Decidua

10.1080/20013078.2020.1812261

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Citations (31)

Restoration of estrogen-dependent progesterone receptor expression in a uterine myocyte cell line

Endocrinology (1993)

Yoel Sadovsky

Journal Article Restoration of estrogen-dependent progesterone receptor expression in a uterine myocyte cell line Get access Y Sadovsky, Y Sadovsky 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143. Search for other works by this author on: Oxford Academic Google Scholar P J Kushner, P J Kushner 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143. Search for other works by this author on: Oxford Academic Google Scholar J M Roberts, J M Roberts 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143. Search for other works by this author on: Oxford Academic Google Scholar R K Riemer R K Riemer 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143. Search for other works by this author on: Oxford Academic Google Scholar Endocrinology, Volume 132, Issue 4, 1 April 1993, Pages 1609–1613, https://doi.org/10.1210/endo.132.4.8462459 Published: 01 April 1993

Progesterone receptor

10.1210/en.132.4.1609

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Citations (5)

N-Myc Down-regulated Gene 1 Modulates the Response of Term Human Trophoblasts to Hypoxic Injury

Journal of Biological Chemistry (2005)

Baosheng Chen D. Michael Nelson Yoel Sadovsky

10.1074/jbc.m507330200

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Citations (139)

Peroxisome Proliferator-Activated Receptor-γ and Retinoid X Receptor Signaling Regulate Fatty Acid Uptake by Primary Human Placental Trophoblasts

The Journal of Clinical Endocrinology & Metabolism (2005)

W. Timothy Schaiff İbrahim Bildirici Monica Cheong Peggy L. Chern D. Michael Nelson

Context: Transplacental transfer of fatty acids from the maternal to the fetal circulation is essential for fetal development. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) regulates fatty acid transport and storage in adipocytes and other cell types. Objective: This study tested the hypothesis that PPARγ and its heterodimeric nuclear receptor partner, retinoid X receptor (RXR), regulate fatty acid uptake by human trophoblasts. Design: Prospective basic laboratory in vitro research was conducted using primary term human trophoblasts. Setting: The study was performed in the perinatal biology laboratory of an academic medical center. Patients or Other Participants: Study materials were obtained from healthy pregnant women at a gestational age of 37–41 wk. Interventions: There were no interventions. Main Outcome Measures: Fat uptake and accumulation in human placental trophoblasts were measured. Results: We initially demonstrated that activation of PPARγ and/or RXR with selective agonists increased the accumulation of neutral lipids in trophoblasts as well as uptake of free fatty acids. Furthermore, activation of PPARγ and RXR enhanced the expression of the fat droplet-associated protein adipophilin along with fatty acid transport protein (FATP)4, whereas expression of FATP2 was decreased by activation of RXR. Finally, we found that inhibition of p38 MAPK, which diminishes the activity of PPARγ in trophoblasts, inhibited fatty acid uptake and blocked the PPARγ- and RXR-dependent increases in adipophilin and FATP4 expression, yet stimulated the expression of FATP1, FATP2, and FATP3. Conclusions: These data support a role for PPARγ and RXR in regulation of fatty acid transport and storage in human placental trophoblasts.

Retinoid X receptor

10.1210/jc.2004-2265

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Citations (158)

“Only a Life Lived for Others Is Worth Living”: Redox Signaling by Oxygenated Phospholipids in Cell Fate Decisions

Antioxidants and Redox Signaling (2017)

Yulia Y. Tyurina Indira H. Shrivastava Vladimir A. Tyurin Gaowei Mao Haider H. Dar

Significance: Oxygenated polyunsaturated lipids are known to play multi-functional roles as essential signals coordinating metabolism and physiology. Among them are well-studied eicosanoids and docosanoids that are generated via phospholipase A2 hydrolysis of membrane phospholipids and subsequent oxygenation of free polyunsaturated fatty acids (PUFA) by cyclooxygenases and lipoxygenases. Recent Advances: There is an emerging understanding that oxygenated PUFA-phospholipids also represent a rich signaling language with yet-to-be-deciphered details of the execution machinery—oxygenating enzymes, regulators, and receptors. Both free and esterified oxygenated PUFA signals are generated in cells, and their cross-talk and inter-conversion through the de-acylation/re-acylation reactions is not sufficiently explored. Critical Issues: Here, we review recent data related to oxygenated phospholipids as important damage signals that trigger programmed cell death pathways to eliminate irreparably injured cells and preserve the health of multicellular environments. We discuss the mechanisms underlying the trans-membrane redistribution and generation of oxygenated cardiolipins in mitochondria by cytochrome c as pro-apoptotic signals. We also consider the role of oxygenated phosphatidylethanolamines as proximate pro-ferroptotic signals. Future Directions: We highlight the importance of sequential processes of phospholipid oxygenation and signaling in disease contexts as opportunities to use their regulatory mechanisms for the identification of new therapeutic targets.

10.1089/ars.2017.7124

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Citations (33)

Identifying the Critical Gaps in Research on Sex Differences in Metabolism Across the Life Span

Endocrinology (2017)

Jane E.B. Reusch T. Rajendra Kumar Judith G. Regensteiner Philip Zeitler Zoltàn Arany

The National Institutes of Health (NIH) Office of Research in Women's Health now functions under a mandate calling for the systematic inclusion of both female and male cells, animals, and human subjects in all types of research, so that sex as a biological variable is understood in health and disease. Sex-specific data can improve disease prevention, diagnosis, and treatment as well as reduce inequities. Inclusion of women in research studies has modestly improved over the last 20 years, yet preclinical research is still primarily done using male animal models and male-derived cells, with the result that many conclusions are made based on incomplete and sex-biased data. There are important, yet poorly studied, sex differences in cardiometabolic disease. To begin to address these sex differences, the Center for Women's Health Research at the University of Colorado held its inaugural National Conference, "Sex Differences Across the Lifespan: A Focus on Metabolism," in September 2016 (cwhr@ucdenver.edu). Research to address the important goal of understanding key sex differences in cardiometabolic disease across the life span is lacking. The goal of this article is to discuss the current state of research addressing sex differences in cardiometabolic health across the life span, to outline critical research gaps that must be addressed in response to NIH mandates, and, importantly, to develop strategies to address sex as a biological variable to understand disease mechanisms as well as develop diagnostic and therapeutic modalities.

Life span

Mandate

Modalities

10.1210/en.2017-03019

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Citations (35)

50: The influence of maternal obesity and diabetes on placental lipid trafficking

American Journal of Obstetrics and Gynecology (2008)

Christina Scifres Baosheng Chen D. Michael Nelson Yoel Sadovsky

10.1016/j.ajog.2008.09.072

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Citations (1)