zearalenone and Endometrial-Hyperplasia

The experiment involved 30 clinically healthy prepubertal bitches aged approximately 70 days with an estimated initial body weight (BW) of 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was administered 50 μg zearalenone (ZEN)/kg BW per os for 42 days, group EII received 75 μg zearalenone/kg BW per os for 42 days, and the control group was administered placebo per os for 42 days. The bitches were hysterectomized at the end of treatment, and samples of uterine tissue were collected for histological and morphometric analyses. The results of the study indicate that exposure to very low doses of ZEN (100% and 150% of the NOAEL) causes simple glandular hyperplasia of the endometrium accompanied by adenogenesis, angiogenesis, and vasodilatation with the related consequences. The noted changes were more pronounced in group EI and less visible in group EII in comparison with group C, which could be indicative of a hormetic dose response.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Endometrial Hyperplasia; Endometrium; Estrogens, Non-Steroidal; Female; Sexual Maturation; Uterus; Zearalenone

Zearalenone (ZEA), a nonsteroidal mycotoxin with estrogen-like activity, is synthesized by molds (Fusarium) commonly contaminating poorly stored agricultural products and foodstuffs. Human ER binds ZEA and this is probable mechanism of its action, although their influence on target tissues seems to be weaker (80-160 less active) comparing to E2. Zea has been observed to possess tumor-promoting activity similar to that of estrogens and hypothetically can inducing proliferation and carcinogenesis in estrogen-dependent tissues. Nowadays, the questions are, if ZEA is present in human endometrium and whether concentrations of this mycoestrogen is associated with endometrial cell proliferation. Endometrial tissues specimens were collected from 49 women (endometrial adenocarcinoma n = 27, endometrial hyperplasia n = 11, normal proliferative endometrium n = 11). Mean tissue zearalenone concentration in 3 endometrial hyperplasia and 22 adenocarcinoma samples was 47.8 +/- +/- 6.48 and 167 +/- +/- 17.69 ng/ml respectively in contrary to normal endometrium where tissue mycoestrogen concentration was not detectable. In 8 cases of hyperplastic and 5 cases of neoplastic endometrial tissue specimens ZEA was not observed. Our findings confirm the presence of ZEA in hyperplastic and neoplastic endometrium and therefore this substance might be of importance in carcinogenesis.

Topics: Adenocarcinoma; Adult; Aged; Biopsy; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Estrogens, Non-Steroidal; Female; Humans; Middle Aged; Retrospective Studies; Zearalenone

The efficacy of dietary tamoxifen (TAM) to alleviate the hyperestrogenic effects of the mycotoxin zearalenone (ZEN) was assessed by pathologic examination of the reproductive organs of female mink (Mustela vison). Mink were fed 20 mg/kg ZEN, 10 mg/kg TAM, or 20 mg/kg ZEN + 10 mg/kg TAM from about 2 mo prior to breeding until the kits reached 3 w of age. All female mink fed ZEN mated, but only 25% whelped. No mink fed TAM or TAM + ZEN mated. Postmortem examination revealed moderate to severely distended uteri filled with caseated necrotic substances in the TAM, ZEN and ZEN + TAM fed mink. Histologic examination revealed mild to severe endometrial hyperplasia to uterine atrophy, endometritis, metritis and pyometra. Ovarian follicles were atrophied and degenerated. TAM was not effective in alleviating the hyperestrogenic effects of ZEN but was a potent estrogen agonist in mink.

Topics: Animals; Dose-Response Relationship, Drug; Drug Interactions; Endometrial Hyperplasia; Endometritis; Estrogen Antagonists; Estrogens, Non-Steroidal; Female; Mink; Necrosis; Ovarian Follicle; Random Allocation; Tamoxifen; Uterus; Zearalenone