The rat prepubertal uterine myometrium and not the luminal epithelium is predominantly affected by a chronic dietary genistein exposure

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Current knowledge about dietary soy isoflavone-induced hormonal effects and potential priming effects for the responsiveness of the organism to other estrogens is insufficient. The present study examined the effects of pre- and postnatal soy isoflavone exposure on estrogen responsiveness by estrogen receptor agonists in the uteri of prepubertal Wistar rats. To this end, offspring were generated from dams already maintained on three dietary groups, (1) a phytoestrogen-free diet, (2) a soy isoflavone-rich diet with 232 ppm daidzein and 240 ppm genistein or (3) a custom-made diet supplemented with 700 ppm genistein (GEN). Then, F1 females continuously exposed to isoflavones from GD1 to PND21 and non-exposed controls were subjected to an immature uterotrophic assay to compare physiological parameters and the response to subcutaneous treatment with 17β-estradiol, GEN or an estrogen receptor subtype (ERα and ERβ)-specific agonist. Uterine wet weight (UWW), luminal epithelial height (LEH) and myometrial thickness (MMT) were determined. In addition, isoflavone plasma levels and mRNA expression profiles of relevant steroid receptors and of molecular markers for proliferation and estrogenicity were assessed for all groups. The influence of dietary isoflavones on the sensitivity to various estrogenic stimuli in these prepubertal animals was minor. Yet, the uterus of immature rats with high chronic GEN exposure alone showed already an increase in UWW, LEH and MMT. The myometrial response to GEN was more pronounced than that of the luminal epithelium, which may be due to a non-uniform distribution of steroid receptors, in particular the progesterone receptor. In conclusion, although the impact of a continuous, prenatally initiated exposure to dietary isoflavones on the uterine physiology of juvenile rats is modest, the possible priming effects of this exposure for beneficial or adverse late-onset consequences in adults should not be neglected.

Details

Original languageEnglish
Pages (from-to)1899-910
Number of pages12
JournalArchives of Toxicology
Volume86
Issue number12
Publication statusPublished - Dec 2012
Peer-reviewedYes

External IDs

researchoutputwizard legacy.publication#45160
PubMed 22811025
Scopus 84871190000

Keywords

Keywords

  • Animals, Body Weight/drug effects, Diet, Epithelium/drug effects, Estrogen Receptor alpha/drug effects, Estrogen Receptor beta/drug effects, Female, Gene Expression Regulation/drug effects, Genistein/blood, Isoflavones/blood, Myometrium/drug effects, Organ Size/drug effects, Phytoestrogens/blood, Pregnancy, RNA/biosynthesis, RNA, Messenger/biosynthesis, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Receptors, Progesterone/drug effects, Sexual Maturation, Uterus/drug effects