A new model of development of the mammalian ovary and follicles

Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.Katja Hummitzsch, Helen F. Irving-Rodgers, Nicholas Hatzirodos, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Dagmar Wilhelm and Raymond J. Rodger

Cost-effectiveness of combination therapy versus antidepressant therapy for management of depression in Japan

Objective: Major depression is expected to become the second leading contributor to disease burden worldwide by 2020. Only a few studies, however, have compared the cost-effectiveness of a combination of cognitive behavioural therapy and antidepressant therapy versus antidepressant therapy alone. The purpose of the present study was therefore to analyse cost-effectiveness, from the perspective of the health-care system and also from a social perspective, comparing combined cognitive behavioural therapy + antidepressant therapy and antidepressant therapy alone in the Japanese setting. Method: A formal decision analytical model was constructed. The analyses were performed from both the perspective of the health-care system and the societal perspective. The clinical outcomes were determined from published articles and reports of expert panels. Because no patient-level data were available, deterministic costing of the different treatment strategies was carried out. Cost-effectiveness was assessed first by determining the incremental cost-effectiveness ratio (ICER) per successfully treated patient, and then by the ICER per quality-adjusted life years (QALYs). Results: The combined therapy increased the rate of successfully treated patients, QALY of severe depression and QALY of moderate depression by 0.15, 0.08 and 0.04, respectively. The combined therapy proved to be more expensive from the health-care system perspective, but the incremental costs were completely offset by the considerable reduction of productivity loss from the social perspective. From the health-care perspective, the ICER per successfully treated patient, ICER per QALY of severe depression and ICER per QALY of moderate depression were JPY 140 418, JPY 268 550 and JPY 537 100, respectively. All the ICERs appeared to be negative from the social perspective. Conclusion: The combined therapy appeared to be cost-effective from the health-care system perspective and the dominant strategy from the social perspective