Dioxins in ascites and serum of women with endometriosis: a pilot study

Lv, Cai; Izumi, Shinichi; Suzuki, Takahiro; Goya, Kenichi; Nakamura, Eri; Sugiyama, Taro; Kobayashi, Hiromi

doi:10.1093/humrep/deq312

Cited by 28 publications

(16 citation statements)

References 37 publications

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“…Indeed, growing evidence suggests that the peritoneal fluid plays a critical role in the implantation and progression of endometriosis (revised by Koninckx et al 1998). Peritoneal fluid contains detectable levels of dioxin or dioxin-like compounds such as 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) depending on individual exposure (Cai et al 2011) and it has been recently shown that the adipose tissue from the omentum in women with endometriosis contains a greater amount of dioxin-like compounds when compared with age and body mass index-matched controls (Martinez-Zamora et al 2015). One can speculate that such compounds are involved in endometriosis as they can transcriptionally induce CYP1B1 and CYP1A1 in explant cultures of human endometrial or stromal cells (Bofinger et al 2001), mostly by their interaction with nuclear receptors, as the resulting complexes bind to the regulatory region of the gene and modulate CYP expression (Waxman 1988).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Piccinato¹,

Neme²,

Torres³

et al. 2016

Reproduction

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Endometriosis is an estrogen-dependent disease affecting up to 10% of all premenopausal women. There is evidence that different endometriosis sites show distinct local estrogen concentration, which, in turn, might be due to a unique local estrogen metabolism. We aimed to investigate whether there was a site-specific regulation of selected enzymes responsible for the oxidative metabolism of estrogens in biopsy samples and endometrial and endometriotic stromal cells. Cytochrome P450 (CYP) 1A1 and CYP1B1 mRNA and protein expressions in deep-infiltrating (rectal, retossigmoidal, and uterossacral) lesions, superficial (ovarian and peritoneal) lesions, and eutopic and healthy (control) endometrium were evaluated by real-time PCR and western blot. Using a cross-sectional study design with 58 premenopausal women who were not under hormonal treatment, we were able to identify an overall increased CYP1A1 and CYP1B1 mRNA expression in superficial lesions compared with the healthy endometrium. CYP1A1 mRNA expression in superficial lesions was also greater than in the eutopic endometrium. Interestingly, we found a similar pattern of CYP1A1 and CYP1B1 expression in in vitro stromal cells isolated from ovarian lesions (n = 3) when compared with stromal cells isolated from either rectum lesions or eutopic endometrium. In contradiction, there was an increased half-life of estradiol (measured by HPLC-MS-MS) in ovarian endometriotic stromal cells compared with paired eutopic stromal endometrial cells. Our results indicate that there is a site-dependent regulation of CYP1A1 and CYP1B1 in ovarian/peritoneal lesions and ovarian endometriotic stromal cells, whereas a slower metabolism is taking place in these cells.

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Section: Discussionmentioning

confidence: 99%

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Piccinato¹,

Neme²,

Torres³

et al. 2016

Reproduction

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“…Dioxin exposure (47,324) and exposure to the a phthalate BzBP metabolite and its metabolites MBz, P and the DEP metabolite MEP may be associated with increased risk of endometriosis (63), although BPA exposure was not linked in an epidemiological study of women with endometriosis (350). One large cross-sectional study from the United States demonstrated an association of MBP with an increased risk of endometriosis (366), and another did not confirm the associations of phthalate exposure with endometriosis and demonstrated that MEHP had an inverse association with the presence of endometriosis (351).…”

Section: Endocrine Disrupting Chemicalsmentioning

confidence: 99%

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Hart

2016

Physiological Reviews

170

119

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Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.

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“…58 The increased incidence of endometriosis being noted in areas of high xenoestrogen exposure 59 raises the question whether the genetic defect developed first in the mother because of her prior exposure, or was caused by the de novo exposure of the offspring to xenoestrogen in utero. In either case, the link of endometriosis and xenoestrogens such as dioxin, 60 at least in select cases, has been established.…”

Section: Geneticsmentioning

confidence: 99%

Paradigm Shift: The Realization of New Medical Alternatives to Surgery for Endometriosis

Lichten¹

2016

j restorat med

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Endometriosis is one of the most destructive benign diseases of women. It is established as developing and being present in upward of 70% of adolescents who do not experience relief of menstrual pain with use of oral contraceptives and antiinflammatory drugs. It occurs in 8%-10% of women in the United States and is most prevalent in developed countries. Symptoms of endometriosis include disabling pain, hemorrhagic uterine bleeding, and infertility. Women with disease can expect a 12% hysterectomy rate. While present medical therapy may offer relief of many symptoms, there have been no major new directions in pharmacologic therapy since leuprolide acetate was made available in 1977. Danazol remains the only alternative to GnRH agonists with proven efficacy and reasonable side effects, according to Cochrane Reviews, yet, it is underused, and GnRH agonists are favored even when Danazol in combination seems more effective. A previously published case report on use of the combination of nandrolone and stanozolol to treat a young woman scheduled for hemicolectomy is discussed as an alternative to surgery along with the limits of standard therapy. This review will focus on recent research and theories seeking to establish causation for disease and offer treatment recommendations.

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Dioxins in ascites and serum of women with endometriosis: a pilot study

Abstract: This is the first report suggesting that higher concentrations of dioxins (PCDDs and PCDFs) in peritoneal fluid are linked to endometriosis. More detail and epidemiological research is warranted to further explore this link.

Cited by 28 publications

References 37 publications

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Paradigm Shift: The Realization of New Medical Alternatives to Surgery for Endometriosis

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