Phthalates alter cell proliferation and apoptosis via crosstalk between MAPK, NF-kB, PI3K/Akt, and NR. Phthalates modulate the activity of signaling pathways, such as MAPK, NF- κB, and PI3K/Akt, to delay apoptosis and stimulate cell proliferation. These activities could lead to prostate and ovarian cancer onset 110,201. DnBP induced cancer onset via the interaction with ER and the modulation of the MAPK signaling pathway . In the study by Giammona et al. , MEHP was administered orally to several rodent species and strains (1 g/kg to gld and B6 mice and Sprague-Dawley rats; 2 g/kg to Fisher rats). Maternal exposure to DEHP at 40 μg/kg inhibited the DNA methylation of Igf2r and Peg3 genes in F1 and F2 mouse oocytes . Depending on the number of generations affected by epigenetic influence, there are transgenerational or multigenerational effects .
Altered reproductive health can be influenced by phthalates’ impact on the hormonal system. Higher levels of estradiol stimulate cell proliferation and growth, leading to the onset of hormone-dependent types of cancer, such as ovarian, uterine, and cervical cancers 169,170. In addition, a US study recruited 3003 women aged 25–85, most of whom were non-Hispanic white, whereby 20 of them were diagnosed with ovarian cancer. This study reported significantly higher urinary levels of MBP and lower levels of MEHP in women with leiomyoma . This study showed that the urinary levels of MECPP were higher in women with leiomyoma than in control subjects .
To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. Comprehensive testosterone profiling, combined with clinical scores could be essential for clarifying the impact of endocrine disruptors on reproductive health. Thus, the work of Woodward and colleagues should gain credibility because of the intelligent way they stratified the population of men by age and the population of phthalates by, in this case, molecular weight.
Then, an in vitro experiment showed similar results, with the exposure to 10 and 100 μM of DEHP inhibiting meiotic progression in mice . In vitro experiments showed that oocytes from DEHP-exposed female mice at 20 and 40 μg/kg/day induced defects in oocyte meiosis . Phthalate impact on female reproduction will be discussed in the next chapter. Newborns with cryptorchidism are at a 30–50 times increased risk of developing testicular cancer then newborns with descended testis . One of the high risks of testicular cancer occurrence is cryptorchidism.
Now, Woodward and colleagues report on their analysis of data collected by the CDC linking phthalate exposure to blood levels of testosterone in almost 15,000 men nationwide. We have known for a long time that certain phthalates can lower blood levels of testosterone in male rats and mice. It is possible that exogenous exposures, such as phthalates, may interact with hormones differently at different concentrations. It is possible that phthalates may exert nonmonotonic affects hormone concentrations as has been noted with other endocrine-disrupting chemicals such as bisphenol A (53, 54).

Gender: Female

Social links