Effects of bis(2-butoxyethyl) phthalate exposure in utero on the development of fetal Leydig cells in rats

Liu, Miaoqing; Chen, Haiqiong; Dai, Haipeng; Zhou, Lu; Wang, Yiyan; Xin, Xiu; Chen, Congde; Li, Zhongrong

doi:10.1016/j.toxlet.2021.08.008

Cited by 7 publications

(6 citation statements)

References 58 publications

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“…In-utero exposure to diisononyl phthalate (DiNP) caused a reduction in fetal testosterone and Insl3 levels in male rats ( 249 ). Similar outcomes were observed with the exposure to unique phthalates such as bis (2-butoxyethyl) phthalate (BBOP) which contains oxygen atoms in the carbon backbone ( 250 ). In-vivo studies were conducted with mixtures of different phthalates to study their combined effect on testicular testosterone production.…”

Section: In Utero Phthalates Exposure and Testicular Functionsmentioning

confidence: 54%

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Basak,

Varma,

Duttaroy

2023

Front. Endocrinol.

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Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-β estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming in utero. On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.

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Section: In Utero Phthalates Exposure and Testicular Functionsmentioning

confidence: 54%

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Basak,

Varma,

Duttaroy

2023

Front. Endocrinol.

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“…Once caspase-3 is activated, apoptosis will be irreversible, and the activation of the apoptotic pathway will promote a large amount of apoptosis of embryonic villus cells, causing the embryo to stop developing [ 30 ]. The serine/threonine protein kinase Akt is a known oncogene that regulates many processes, including metabolism, proliferation, cell survival, and growth [ 31 ]. Studies have demonstrated that dibutyl phthalate is toxic to embryos by regulating AKT1 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…The serine/threonine protein kinase Akt is a known oncogene that regulates many processes, including metabolism, proliferation, cell survival, and growth [ 31 ]. Studies have demonstrated that dibutyl phthalate is toxic to embryos by regulating AKT1 [ 31 ]. Insulin-like growth factor 1 (IGF-1) has long been known to play a role in promoting growth and development, especially in regulating embryonic growth and development [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology

Liu

Yang

Yang³

et al. 2023

Toxins

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Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

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“…After adapting to the new environment for 7 d, rats were randomly divided into 5 groups (6 in each group): 0 (corn oil as the control), 10, 100, 250, and 500 mg/kg BBOP. Dosage selection was based on our previous study that showed BBOP disrupted fetal Leydig cell function after gestational exposure to up to 500 mg/kg BBOP 28 . BBOP was dissolved in corn oil.…”

Section: Methodsmentioning

confidence: 99%

“…Dosage selection was based on our previous study that showed BBOP disrupted fetal Leydig cell function after gestational exposure to up to 500 mg/kg BBOP. 28 BBOP was dissolved in corn oil. All rats were dosed via gavage at a volume of 2 ml/kg body weight from 9:00 a.m. every day.…”

Section: Animal Experimentsmentioning

confidence: 99%

Effects of bis (2‐butoxyethyl) phthalate on adrenocortical function in male rats in puberty partially via down‐regulating NR5A1/NR4A1/NR4A2 pathways

Liu

Chen

Dai

et al. 2022

Environmental Toxicology

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Phthalates may interfere with the biosynthesis of steroid hormones in the adrenal cortex. Bis (2-butoxyethyl) phthalate (BBOP) is a phthalate containing oxygen atoms in the alcohol moiety. In this study, 35-day-old male Sprague-Dawley rats were daily gavaged with BBOP (0, 10, 100, 250, and 500 mg/kg body weight) for 21 days.BBOP did not affect the weight of body and adrenal glands. BBOP significantly reduced serum corticosterone levels at 250 and 500 mg/kg, and lowered aldosterone level at 500 mg/kg without affecting adrenocorticotropic hormone. BBOP did not alter the thickness of the adrenal cortex. BBOP significantly down-regulated the expression of steroidogenesis-related genes (Scarb1, Star, Cyp11a1, Cyp21, Cyp11b1, Cyp11b2, Nr5a1, Nr4a1, and Nr4a2) and proteins, and antioxidant enzymes (Sod1, Sod2, Gpx1, and Cat) and their proteins, while up-regulating the expression of Mc2r and Agtr1a at various doses. BBOP reduced the phosphorylation of AKT1, AKT2, and ERK1/2, as well as the levels of SIRT1 and PGC1α without affecting the phosphorylation of AMPK. BBOP significantly induced the production of reactive oxygen species and apoptosis rate in H295R cells at 100 μM and higher after 24 h of treatment. In conclusion, male rats exposed to BBOP in puberty have significant reduction of steroid biosynthesis with a potential mechanism that is involved in the decrease in the phosphorylation of AKT1, AKT2, ERK1/2, as well as SIRT1 and PGC1α and increase in ROS.

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Effects of bis(2-butoxyethyl) phthalate exposure in utero on the development of fetal Leydig cells in rats

Cited by 7 publications

References 58 publications

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology

Effects of bis (2‐butoxyethyl) phthalate on adrenocortical function in male rats in puberty partially via down‐regulating NR5A1/NR4A1/NR4A2 pathways

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