Tris(1,3‐dichloro‐2‐propyl) phosphate disturbs mouse embryonic development by inducing apoptosis and abnormal DNA methylation

Abstract

Tris(1,3‐dichloro‐2‐propyl) phosphate (TDCPP) is a kind of additive flame retardants (FRs) and was found to affect early embryonic development in zebrafish; however, there are few studies to investigate whether TDCPP will disturb the development of early mouse embryos. In our studies, we used mouse embryos as models to study the toxicology of TDCPP on the early embryos. The results showed that TDCPP disturbed the development of early mouse embryos in a dose‐dependent manner. 10 μM TDCPP decreased the blastocyst formation and 100 μM TDCPP was a lethal concentration for the mouse embryos. We proved that TDCPP was detrimental to embryonic development potential by increasing the reactive oxygen species level and inducing early apoptosis. Furthermore, TDCPP changed the DNA methylation patterns of imprinted genes in treated blastocysts. The methylation of H19 and Snrpn promoter regions was increased from 37.67% to 46.00% and 31.56% to 44.38% in treated groups, respectively. In contrast, Peg3 promoter region methylation was declined from 86.55% to 73.27% in treated embryos. Taken together, our results demonstrated that TDCPP could adversely impair the early embryonic development in mouse. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Organophosphate Flame Retardants in Pregnant Women: Sources, Occurrence, and Potential Risks to Pregnancy Outcomes

“…Exposure to OPFRs during the embryonic stage also affects brain development by damaging the normal function of the rat placenta . Early mouse embryo development was dose-dependently inhibited by TDCIPP (Oral LD50 = 2250 mg/kg), with 10 μM TDCPP reducing blastocyst formation and 100 μM TDCIPP being deadly to mice embryos . Acute exposure to TPHP (Oral LD50 = 1320 mg/kg) inhibited mouse embryonic stem cell growth in a dose-dependent manner .…”

“…144 Early mouse embryo development was dosedependently inhibited by TDCIPP (Oral LD50 = 2250 mg/ kg), with 10 μM TDCPP reducing blastocyst formation and 100 μM TDCIPP being deadly to mice embryos. 145 Acute exposure to TPHP (Oral LD50 = 1320 mg/kg) inhibited mouse embryonic stem cell growth in a dose-dependent manner. 132 It is noteworthy that specific concentrations of OPFRs causing developmental toxicity, neurotoxicity, cardiotoxicity, and hepatotoxicity in zebrafish are within the upper limit of the levels of OPFRs in indoor dust, human breast milk, plasma, and urine.…”

Regulation of Developmental Cell Death in the Animal Kingdom: A Critical Analysis of Epigenetic versus Genetic Factors

“…As mentioned above, a general epigenetic modification rule accounting for cell death in different systems cannot be expected, as distinct modifications may favor cell death in distinct cell populations. Among the epigenetic signatures proposed to be associated with normal or abnormal developmental dying processes are histone modifications [71][72][73][74] and/or promoter methylation of specific genes, including master transcription factors [75,76], genes encoding secreted factors [77], or tumor suppressor and cell death regulatory genes [78,79].…”

Tris(1,3-dichloro-2-propyl) phosphate disrupts cellular metabolism within human embryonic kidney (HEK293) cells

“…In 2011, TDCIPP was added to California’s Proposition 65 (Prop 65) list based on its potential to cause cancer following ingestion [ 7 ]. In addition to being a suspected carcinogen, TDCIPP impacts DNA methylation within zebrafish and mice during early embryonic development [ 8 – 12 ]. Moreover, TDCIPP has been associated with adverse pregnancy outcomes within human cohorts [ 13 – 15 ].…”