Prenatal exposure to a mixture of different phthalates increases the risk of mammary carcinogenesis in F1 female offspring

Freitas, Thiago de; Zapaterini, Joyce R.; Moreira, Cristiane Menabo; Aquino, Ariana Musa de; Alonso-Costa, Luiz G; Bidinotto, Lucas Tadeu; Kass, Laura; Flaws, Jodi A.; Scarano, Wellerson Rodrigo; Barbisan, Luı́s Fernando

doi:10.1016/j.fct.2021.112519

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…BBzP [130], mix of DEP + DEH P + DBP + DiBP + DiNP + BBzP [129]; VO: DBP [133]), methyl paraben [66] DES [120], genistein [120], o,p'-DDT [120], PFOA [126,127], phthalates (VO: DEHP [134,135], DBP [133]), methyl paraben [66], triclosan [66] Delayed puberty (thelarche) Human PCDD/F [96], PFOA [99,102,103], phthalates (MEHP [91], MBzP [105], DEHP [105]) b Dioxin-like compounds (unspecified) [97], b DDE [98], hexachlorobenzene [98], benzophenone-3 [93], enterolactone [93], b PCBs [98], b PBDEs [98], phthalates (MBzP [112], DEHP [107])…”

Section: Experimental Studiesmentioning

confidence: 99%

“…Rodent Bisphenols (BPA [139,227,[232][233][234] (also sensitizes to DMBA [233,[237][238][239]), BPS [117,229], BPAF [117]), PCBs [242] (also sensitize to DMBA and MNU [242]), TCDD sensitizes to DMBA [240], phthalate mixture sensitizes to MNU [129] BPA sensitizes to DMBA [238] Pharmaceutical hormones [138],…”

Section: Experimental Studiesmentioning

confidence: 99%

“…Remarkably, prenatal exposure to higher molecular weight phthalates is associated with delayed thelarche in humans [91,105] and delayed vaginal opening in rodents [130,131], but pubertal development of the rodent MG appears to be accelerated by prenatal exposure to high molecular weight phthalates [129,130] and delayed with low molecular weight phthalates [132]. Conversely, peripubertal levels of phthalates in humans are usually associated with earlier thelarche [106][107][108][109][110][111], and postnatal exposure in rodents accelerated vaginal opening [133][134][135].…”

Section: Intersection Of Epidemiological and Experimental Studiesmentioning

confidence: 99%

“…The effects of phthalates on pubertal indices in rats also vary with WoS, dose, and chemical species. Perinatal exposure to higher molecular weight phthalates tended to increase MG proliferation and differentiation [ 129 , 130 ] but interestingly, such exposures tended to delay vaginal opening [ 130 , 131 ]. On the other hand, perinatal exposure to dibutyl phthalate (DBP; low molecular weight) in rats led to hypoplasia and poor ductal branching in the pubertal female MG, as well as nipple retention and MG degeneration in young and adult males, respectively [ 132 ].…”

Section: Pubertymentioning

confidence: 99%

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Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities

Kay

Cardona²,

Rudel³

et al. 2022

Curr Envir Health Rpt

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Population studies show worrisome trends towards earlier breast development, difficulty in breastfeeding, and increasing rates of breast cancer in young women. Multiple epidemiological studies have linked these outcomes with chemical exposures, and experimental studies have shown that many of these chemicals generate similar effects in rodents, often by disrupting hormonal regulation. These endocrine-disrupting chemicals (EDCs) can alter the progression of mammary gland (MG) development, impair the ability to nourish offspring via lactation, increase mammary tissue density, and increase the propensity to develop cancer. However, current toxicological approaches to measuring the effects of chemical exposures on the MG are often inadequate to detect these effects, impairing our ability to identify exposures harmful to the breast and limiting opportunities for prevention. This paper describes key adverse outcomes for the MG, including impaired lactation, altered pubertal development, altered morphology (such as increased mammographic density), and cancer. It also summarizes evidence from humans and rodent models for exposures associated with these effects. We also review current toxicological practices for evaluating MG effects, highlight limitations of current methods, summarize debates related to how effects are interpreted in risk assessment, and make recommendations to strengthen assessment approaches. Increasing the rigor of MG assessment would improve our ability to identify chemicals of concern, regulate those chemicals based on their effects, and prevent exposures and associated adverse health effects.

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Section: Experimental Studiesmentioning

confidence: 99%

Section: Experimental Studiesmentioning

confidence: 99%

Section: Intersection Of Epidemiological and Experimental Studiesmentioning

confidence: 99%

Section: Pubertymentioning

confidence: 99%

See 2 more Smart Citations

Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities

Kay

Cardona²,

Rudel³

et al. 2022

Curr Envir Health Rpt

View full text Add to dashboard Cite

show abstract

“…17 Previously, our group showed that the phthalate mixture (based on Reference 9) exposure during gestation and lactation caused dysfunction in ovarian folliculogenesis and steroidogenesis in F1 and F2 females 18 and increased the breast cancer susceptibility in F1 adult female rats after a chemical-induced carcinogenesis protocol. 19 In male offspring, in addition to altering phenotypic parameters in the prostate of prepubertal, adults and aged rats, 15,16 the phthalate mixture exposure from GD10 to PND21 modulated the transcriptome and miRNAome (especially the rno-miR-184 and rno-miR-141-3p) as well as the proteomic profile in offspring maternally exposed to the same set of phthalates. 15,16 Other investigations have demonstrated that prenatal phthalate exposure can deregulate biomarkers of reproductive aging 20 and prostate oncogenic process in offspring.…”

Section: Introductionmentioning

confidence: 99%

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

Aquino,

Fioretto,

Alonso‐Costa

et al. 2024

Environmental Toxicology

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A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno‐miR‐184 and rno‐miR‐141‐3p in the ventral prostate (VP) of offspring. Here, rno‐miR‐184 and rno‐miR‐141‐3 expressions were obtained by RT‐qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21‐F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 μg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1‐treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.

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Systematic computational toxicity analysis of the ozonolytic degraded compounds of azo dyes: Quantitative structure-activity relationship (QSAR) and adverse outcome pathway (AOP) based approach

Reddy Ramireddy,

Kurakula,

Velayudhaperumal Chellam

et al. 2023

Environmental Research

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Prenatal exposure to a mixture of different phthalates increases the risk of mammary carcinogenesis in F1 female offspring

Cited by 9 publications

References 49 publications

Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities

Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

Systematic computational toxicity analysis of the ozonolytic degraded compounds of azo dyes: Quantitative structure-activity relationship (QSAR) and adverse outcome pathway (AOP) based approach

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