Bisphenol A Exposure In Utero Disrupts Early Oogenesis in the Mouse

Susiarjo, Martha; Hassold, Terry; Freeman, Edward Augustus; Hunt, Patricia A.

doi:10.1371/journal.pgen.0030005

Cited by 358 publications

(347 citation statements)

References 43 publications

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“…These studies have several limitations, including the analytical methods used and the selection of human subjects. However, studies from rodents suggest that BPA can cause aneuploidy in oocytes (Susiarjo et al 2007) and alter the body weight of offspring resulting from intrauterine transplantation of embryos cultured in media containing BPA (Takai et al 2001). As such, presence of measurable concentrations of unconjugated BPA in follicular fluid is a potential concern.…”

Section: Healthymentioning

confidence: 99%

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Vandenberg

Chahoud

Heindel³

et al. 2012

Ciênc. saúde coletiva

333

331

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Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A Resumo Bisfenol A (BPA) é um dos produtos quí-micos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinéti-ca do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco. Palavras-chave Disruptor endócrino, Exposição humana, Modelo PBPK/PBTK, Gravidez, Avaliação de risco, Toxicocinética Abstract Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

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Section: Healthymentioning

confidence: 99%

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Vandenberg

Chahoud

Heindel³

et al. 2012

Ciênc. saúde coletiva

333

331

View full text Add to dashboard Cite

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“…In the cow, estrogen may block follicle activation by inhibiting meiotic progression. Supporting the idea that estrogen can affect meiotic progression, bisphenol A (BPA) treatment of mouse embryos caused defects in meiosis (Susiarjo et al 2007). ESR2 mutants had meiotic defects similar to BPA-treated animals, suggesting that BPA acts as an ESR2 antagonist.…”

Section: Links Between Meiotic Progression and Follicle Formationmentioning

confidence: 99%

Follicular assembly: mechanisms of action

Pepling¹

2012

Reproduction

211

190

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The differentiation of primordial germ cells (PGCs) into functional oocytes is important for the continuation of species. In mammals, PGCs begin to differentiate into oocytes during embryonic development. Oocytes develop in clusters called germ line cysts. During fetal or neonatal development, germ cell cysts break apart into single oocytes that become surrounded by pregranulosa cells to form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst undergoes cell death with only one-third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control cyst breakdown, oocyte survival, and follicle assembly are currently under investigation. This review describes the mechanisms that have been implicated in the control of primordial follicle formation, which include programmed cell death regulation, growth factor and other signaling pathways, regulation by transcription factors and hormones, meiotic progression, and changes in cell adhesion. Elucidation of mechanisms leading to formation of the primordial follicle pool will help research efforts in ovarian biology and improve treatments of female infertility, premature ovarian failure, and reproductive cancers.

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“…Bronson et al (1995) revealed aneuploidy in humans from several embryonic stem cell-derived male offspring. Treatment of pregnant mice with low, environmentally relevant doses of BPA during mid-gestation translated into an increase in aneuploid eggs and embryos in the mature female (Susiarjo et al, 2007). A significant difference was found in aneuploidies between hFVIII transgenic and non-transgenic peripheral blood cells (Parkanyi et al, 2004;unpublished observations) but without any deleterious effect on the health or reproduction of animals.…”

Section: Resultsmentioning

confidence: 98%

Hypodiploidy as a prominent attributor to chromosomal aneuploidy in transgenic rabbit embryos

Roychoudhury¹,

Bulla²,

Čurlej³

et al. 2008

CZECH J ANIM SCI

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Transgenic animals play a vital role in basic research, agriculture and pharmaceutical industries. Rabbits have the advantage of other large laboratory species in that they have a short gestation period and yield large numbers of embryos. Production of transgenic rabbits has been directed towards using the rabbit as a model for large domestic animals or as a basic biological model for studying the mammalian gene regulation. In connection with their use, developmental and health disorders have also been reported in genetically modified animals. Random integration of a transgene can disrupt the function or regulation of an endogenous gene, resulting in insertion mutations or chromosomal aneuploidy. Chromosomal abnormalities affect the developmental potential of early embryos and serve as potential predictors of developmental outcome. This study was aimed at analyzing the cytogenetic profile of transgenic rabbit embryos, which is necessary for selecting optimal lines for dissemination in order to eliminate animals with chromosomal aberrations. Conventional Giemsa stained c-metaphase spreads obtained from blastomeres of intact as well as microinjected transgenic (EGFP and hFVIII) and non-transgenic embryos revealed a significantly higher (P < 0.01) rate of aneuploid cells in transgenic rabbits compared to non-transgenic animals. However, microinjection did not seem to influence the rate of aneuploidy, as the incidence of aneuploidy in non-transgenic blastomeres was significantly lower (P < 0.01) in comparison with intact ones (14.3 vs. 73.33%). The findings suggest hypodiploidy as the prominent attributor to the occurrence of aneuploidy. This is the first report of 100% chromosomal aneuploidy in the embryos of both EGFP and hFVIII transgenic rabbits.

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Bisphenol A Exposure In Utero Disrupts Early Oogenesis in the Mouse

Cited by 358 publications

References 43 publications

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Follicular assembly: mechanisms of action

Hypodiploidy as a prominent attributor to chromosomal aneuploidy in transgenic rabbit embryos

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