Oogenesis/Folliculogenesis & Ovarian Follicle Endocrinology follicle - composite structure Ovarian Follicle that will produce mature oocyte – primordial follicle - germ cell (oocyte) with a single layer ZP of mesodermal cells around it TI & TE it – as development of follicle progresses, oocyte will obtain a ‘‘halo’’ of cells and membranes that are distinct: Oocyte 1. zona pellucide (ZP) 2. granulosa (Gr) 3. theca interna and externa (TI & TE) Gr Summary: The follicle is the functional unit of the ovary. One female gamete, the oocyte is contained in each follicle. The granulosa cells produce hormones (estrogen and inhibin) that provide ‘status’ signals to the pituitary and brain about follicle development. Mammal - Embryonic Ovary Germ Cells Division and Follicle Formation from Makabe and van Blerkom, 2006 Oogenesis and Folliculogenesis GGrraaaafifiaann FFoolliclliclele SStrtruucctuturree SF-1 Two Cell Steroidogenesis • Common in mammalian ovarian follicle • Part of the steroid pathway in – Granulosa – Theca interna • Regulated by – Hypothalamo-pituitary axis – Paracrine factors blood ATP FSH LH ATP Estradiol-17β FSH-R LH-R mitochondrion cAMP cAMP CHOL P450arom PKA 17βHSD C P450scc PKA C C C cholesterol pool PREG Testosterone StAR 3βHSD Estrone SF-1 PROG 17βHSD P450arom Androstenedione nucleus Andro theca Mammals granulosa Activins & Inhibins Pituitary - Gonadal Regulation of the FSH Adult Ovary E2 Inhibin Activin Follistatin Inhibins and Activins •Transforming Growth Factor -β (TGF-β) family •Many gonadal cells produce β subunits •In ovary - only granulosa produce α subunits •At the ovary, inhibins antagonize the actions of activins Activin A Inhibin A βa α Activin AB Inhibin B βb Activin B Moore et al. unpubl. data + Mammals ATP ATP IGF-1 Cholesterol cAMP cAMP + P450scc + + 3βHSD - + Inhibin GDF-9 Progesterone + - - CYP17 Kit Ligand - + BMP-15 Androstenedione Activin + increase thecal proliferation oocyte theca granulosa Three Cell Steroidogenesis • Common in avian/reptilian(?) ovarian follicles • Part of the steroid pathway in – Granulosa – Theca interna – Theca externa • Regulated by – Hypothalamo-pituitary axis – Paracrine factors Preovulatory Follicle Small Follicle Folliculogenesis theca Estradiol-17β 2 Months P450arom Androstenedione Estradiol-17β Androstenedione Estradiol-17β CYP17 P450arom Progesterone theca externa P450arom Androstenedione P450scc Androstenedione 3βHSD Androstenedione CYP17 CYP17 Progesterone Cholesterol Progesterone P450scc 3βHSD medullary theca interna lacunae cells 2 Weeks Cholesterol Progesterone theca interna P450scc 3βHSD No Cholesterol steroidogenesis granulosa granulosa BIRDS Review Mitosis/Meiosis • What events are different? • What events take place in utero in mammal versus later in life? • How is spermatogenesis and oogenesis different?.