Effects of dibenzothiophene, a sulfur‐containing heterocyclic aromatic hydrocarbon, and its alkylated congener, 2,4,7‐trimethyldibenzothiophene, on placental trophoblast cell function

Published on Sep 1, 2021in Journal of Applied Toxicology3.446
· DOI :10.1002/JAT.4128
Sergio Raez-Villanueva3
Estimated H-index: 3
(McMaster University),
Genevieve A. Perono3
Estimated H-index: 3
(McMaster University)
+ 2 AuthorsAlison C. Holloway48
Estimated H-index: 48
(McMaster University)
Worldwide demand for petroleum products has resulted in increased oil and gas activities in many countries. Conventional and unconventional oil and gas extraction, production, and transport lead to increased levels of petroleum-derived polycyclic aromatic hydrocarbons (PAHs) in the environment. PAH exposure has profound effects on reproduction by affecting pathways involved in placental trophoblast cell function and impairing normal placental development and function-key contributors to reproductive success. However, other components found in petroleum and wastewaters from oil and gas extraction, including the sulfur-containing heterocyclic aromatic compounds such as dibenzothiophene (DBT) and its alkylated derivatives, may also impact reproductive success. The goal of this study was to examine the effect of exposure to DBT, a compound commonly detected in the environment, and one of its alkylated analogues, 2,4,7-trimethyldibenzothiophene (2,4,7-DBT), on steroidogenic and angiogenic pathways critical for mammalian development in placental trophoblast cells (HTR-8/SVneo cells). 2,4,7-DBT but not DBT increased estradiol output in association with increased tube-like formation (surrogate for angiogenesis). These changes in angiogenesis did not appear to be related to altered expression of the key placental angiogenic gene targets (ANGPTL4, VEGFA, and PGF). Neither compound showed a concentration related effect on progesterone synthesis or its receptor expression. Our results suggest that 2,4,7-DBT can disrupt key pathways important for placental trophoblast function and highlight the importance of determining the impact of exposure to both parent and alkylated compounds. Further, these data suggest that exposure to sulfur-containing heterocyclic aromatic compounds may lead to placental dysfunction and impact reproductive success at environmentally relevant levels.
#1Philippe ThomasH-Index: 1
#1Ewelina Goryszewska (PAN: Polish Academy of Sciences)H-Index: 5
#2Piotr Kaczyński (PAN: Polish Academy of Sciences)H-Index: 23
Last. Agnieszka Waclawik (PAN: Polish Academy of Sciences)H-Index: 21
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Pregnancy establishment in mammals, including pigs, requires proper communication between embryos and the maternal reproductive tract. Prokineticin 1 (PROK1) has been described as a secretory protein with pleiotropic functions and as a novel tissue-specific angiogenic factor. However, despite the studies performed mainly on human cell lines and in mice, the function of PROK1 in the endometrium during early pregnancy is still not fully elucidated. We hypothesized that PROK1 contributes to pregnan...
#1Susan C. Nagel (MU: University of Missouri)H-Index: 30
#2Christopher D. Kassotis (Duke University)H-Index: 17
Last. V.D. Balise (UNM: University of New Mexico)H-Index: 1
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Abstract Unconventional oil and natural gas extraction (UOG) combines directional drilling and hydraulic fracturing and produces billions of liters of wastewater per year. Herein, we review experimental studies that evaluated the potential endocrine-mediated health impacts of exposure to a mixture of 23 UOG chemicals commonly found in wastewater. The purpose of this manuscript is to synthesize and summarize a body of work using the same UOG-mix but with different model systems and physiological ...
During pregnancy, the maternal cardiovascular system undergoes significant changes, including increased heart rate, cardiac output, plasma volume, and uteroplacental blood flow (UPBF) that are required for a successful pregnancy outcome. The increased UPBF is secondary to profound circumferential growth that extends from the downstream small spiral arteries to the upstream conduit main uterine artery. Although some of the mechanisms underlying uterine vascular remodeling are, in part, known, the...
#1Nicole C. Deziel (Yale University)H-Index: 18
#2Eran Brokovich (Ministry of Energy)H-Index: 1
Last. Keren Agay-Shay (BIU: Bar-Ilan University)H-Index: 7
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Abstract Background Hydraulic fracturing together with directional and horizontal well drilling (unconventional oil and gas (UOG) development) has increased substantially over the last decade. UOG development is a complex process presenting many potential environmental health hazards, raising serious public concern. Aim To conduct a scoping review to assess what is known about the human health outcomes associated with exposure to UOG development. Methods We performed a literature search in MEDLI...
#1Rebecca L. Zur (U of T: University of Toronto)H-Index: 1
#2John Kingdom (U of T: University of Toronto)H-Index: 73
Last. Sebastian R. Hobson (U of T: University of Toronto)H-Index: 11
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Placental dysfunction is a major contributing factor to fetal growth restriction. Placenta-mediated fetal growth restriction occurs through chronic fetal hypoxia owing to poor placental perfusion through a variety of mechanisms. Maternal vascular malperfusion is the most common placental disease contributing to fetal growth restriction; however, the role of rare placental diseases should not be overlooked. Although the features of maternal vascular malperfusion are identifiable on placental path...
#1Zi-Run Tang (CAU: China Agricultural University)H-Index: 2
#2Xue-Ling Xu (CAU: China Agricultural University)H-Index: 3
Last. Kun Yu (CAU: China Agricultural University)H-Index: 12
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Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. So...
Unconventional oil and gas (UOG) extraction (fracking) has increased in the United States, as well as interest in the associated risks and benefits. This study’s purpose was to qualitatively examin...
#1Min Liu (CQMU: Chongqing Medical University)H-Index: 2
#2Ting Deng (CQMU: Chongqing Medical University)H-Index: 1
Last. Xuemei Chen (CQMU: Chongqing Medical University)H-Index: 21
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Abstract Benzo [a]pyrene (BaP) is a well-known endocrine disruptor. Exposure to BaP is known to impair embryo implantation. The corpus luteum (CL), the primary source of progesterone during early pregnancy, plays a pivotal role in embryo implantation and pregnancy maintenance. The inappropriate luteal function may result in implantation failure and spontaneous abortions. However, the effect of BaP on CL remains unknown. This study investigated the deleterious effects of BaP on the structure and ...
#1Cloelle Danforth (Environmental Defense Fund)H-Index: 3
#2Weihsueh A. Chiu (A&M: Texas A&M University)H-Index: 34
Last. Elena Craft (Environmental Defense Fund)H-Index: 8
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Abstract In the United States, onshore oil and gas extraction operations generate an estimated 900 billion gallons of produced water annually, making it the largest waste stream associated with upstream development of petroleum hydrocarbons. Management and disposal practices of produced water vary from deep well injection to reuse of produced water in agricultural settings. However, there is relatively little information with regard to the chemical or toxicological characteristics of produced wa...
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