Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis.

Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2-20 µM) inhibited the proliferation of OESCs (P < 0.05 for 0.2 µM; P < 0.01 for 2 and 20 µM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)ß by an antagonist, PHTPP, or by ERß siRNA (P < 0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE2 levels (P < 0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P < 0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis.

Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle.

Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Accumulated evidence shows that leptin is involved in the stimulation of reproductive functions and that local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta plays a role in early development. To investigate the role of leptin in implantation, we examined the expression of OB-R and leptin in the human endometrium. Northern and Western blot analyses and RT-PCR showed that the long form of OB-R (OB-R(L)) messenger ribonucleic acid (mRNA) and protein were expressed. In contrast, leptin mRNA or protein was not detected. All of the splice variants of OB-R (OB-R(T)) and OB-R(L) transcripts were expressed in 90% and 84% of the cases, respectively. OB-R mRNA expression peaked in the early secretory phase. Decidual tissue of early gestation also expressed OB-R(T) and OB-R(L). Their incidence and abundance were comparable among endometria with benign uterine diseases and disease-free endometria and were not related to a body mass index within the normal range. The present results indicate that OB-R, but not leptin, is expressed in the human endometrium.