Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis

Martínez-Zamora, María Ángeles; Mattioli, L.; Parera, J.; Abad, Esteban; Coloma, José; Babel, B.; Galcerán, M.T.; Balasch, Juan; Carmona, Francisco

doi:10.1093/humrep/dev026

Cited by 55 publications

(38 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, these results although suggestive must be interpreted with caution. While several studies have provided evidence of a potential link significant associations between women with endometriosis and PCB levels could not be demonstrated by other investigators [25,28,31]. No significant association between PCBs and endometriosis risk was found in a study of 789 patients (251 cases; 538 controls); with 20 PCB congers measured in serum from surgically confirmed cases [25].…”

Section: Serum and Omental Fatmentioning

confidence: 89%

See 1 more Smart Citation

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

Freger¹,

Foster²

2021

Endometriosis

View full text Add to dashboard Cite

Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009-2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak.

show abstract

Section: Serum and Omental Fatmentioning

confidence: 89%

“…Trabert et al [25] 251:538 PCBs 18,28,44,49,52,66,74,87,99,101,118,128,138,146,149,151,153,156,157,167,170,172,177,178,180,183,187,189,194,195,196,201,206 Buck-Louis et al [27] 190:283 and 14:113…”

Section: Polychlorinated Biphenyls (Pcbs) Dioxin and Dioxin-like Commentioning

confidence: 99%

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

Freger¹,

Foster²

2021

Endometriosis

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Exposure in the case–control studies was much lower than in Seveso: Six studies reported no difference in blood levels of PCDD/Fs and DL‐PCBs between cases and controls (Pauwels et al., ; Fierens et al., ; De Felip et al., ; Niskar et al., ; Porpora et al., ; Cai et al., ) One reported lower levels in cases than in controls (Tsukino et al., ) Four reported higher levels in endometriosis cases than in controls (Heilier et al., ; Simsa et al., ; Martínez‐Zamora et al., ; Ploteau et al., ). …”

Section: Assessmentmentioning

confidence: 99%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

143

View full text Add to dashboard Cite

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

show abstract

Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis

Abstract: Not applicable.

Cited by 55 publications

References 53 publications

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

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

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Contact Info

Product

Resources

About