Context:Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens.Objective:The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons.Design:The study was performed using human tissue analysis and cell culture.Setting:The study was conducted at a university research institute.Patients:Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18).Main Outcome Measures:mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens.Results:TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P < .001, P < .01). TRPV1, SCN9A, and TAC1 were elevated in endometriosis lesions (P < .05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (P < .05). Incubation of sensory neurons with 17β-estradiol increased TRPV1 mRNA (P < .01). The estrogen receptor-β-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile increased concentrations of TRPV1, P2RX3, SCN9A, and TAC1 mRNAs.Conclusions:Estrogen-dependent expression of TRPV1 in sensory neurons may explain why ovarian suppression can reduce endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

The regenerative potential of the mammalian ovary has been a controversial area over the last decade. Isolation of cells, termed oogonial stem cells (OSCs), from adult rodent and human ovaries has been reported, with these cells exhibiting both germ and stem cell markers in culture. When re-introduced into an ovarian somatic environment these cells have generated follicles capable of producing healthy offspring in rodents, and there is some evidence of human OSCs being able to form oocyte-like structures in a xenotransplant model. Importantly, there are no data on their potential physiological role within the ovary, and specifically no evidence that they contribute to the primordial follicle pool and thus to later stages of follicle development. The cues required for oocyte differentiation from these cells are not well understood either in vivo or in vitro, and these will need to be further elucidated to maximise their potential for therapeutic intervention. OSCs may also be of value as a model to investigate normal human germ cell differentiation. It is likely that their interactions with ovarian somatic cells and/or extracellular signals will be important in these processes. This review summarises our current knowledge on the isolation and characterisation of mammalian oogonial stem cells.