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

Abstract

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.

The effects of polycyclic aromatic compounds (PACs) on mammalian ovarian function

“…Interestingly, however, the observed effects were influenced by alkylation ( Lee et al, 2017 ). Similarly, another study conducted in human placental trophoblast cells reported that the alkylated congener of a petroleum-derived S-containing heterocyclic PAC, 2,4,7-trimethyldibenzothiophene, but not its parent compound dibenzothiophene, significantly increased E2 secretion in association with surrogate markers for angiogenesis ( Raez-Villanueva et al, 2021 ).…”

“…There is considerable evidence that PACs can function as EDCs and negatively affect reproductive function ( Bolden et al, 2017 , Khan et al, 2021 ; Lee et al, 2017 , Raez-Villanueva et al, 2021 ; Zhang et al, 2016 ). However, reports on the impacts of PACs on the ovary in mammals are limited.…”