Prostaglandins and Follicular Functions David T
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Inhibition of Gonadotropin-Induced Granulosa Cell Differentiation By
Proc. Nati. Acad. Sci. USA Vol. 82, pp. 8518-8522, December 1985 Cell Biology Inhibition of gonadotropin-induced granulosa cell differentiation by activation of protein kinase C (phorbol ester/diacylglycerol/cyclic AMP/luteinizing hormone receptor/progesterone) OSAMU SHINOHARA, MICHAEL KNECHT, AND KEVIN J. CATT Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 Communicated by Roy Hertz, August 19, 1985 ABSTRACT The induction of granulosa cell differentia- gesting that calcium- and phospholipid-dependent mecha- tion by follicle-stimulating hormone (FSH) is characterized by nisms are involved in the inhibition of granulosa cell differ- cellular aggregation, expression of luteinizing hormone (LH) entiation. The abilities oftumor promoting phorbol esters and receptors, and biosynthesis of steroidogenic enzymes. These synthetic 1,2-diacylglycerols to stimulate calcium-activated actions of FSH are mediated by activation of adenylate cyclase phospholipid-dependent protein kinase C (14, 15) led us to and cAMP-dependent protein kinase and can be mimicked by examine the effects of these compounds on cellular matura- choleragen, forskolin, and cAMP analogs. Gonadotropin re- tion in the rat granulosa cell. leasing hormone (GnRH) agonists inhibit these maturation responses in a calcium-dependent manner and promote phosphoinositide turnover. The phorbol ester phorbol 12- MATERIALS AND METHODS myristate 13-acetate (PMA) also prevented FSH-induced cell Granulosa cells were obtained from the ovaries of rats aggregation and suppressed cAMP formation, LH receptor (Taconic Farms, Germantown, NY) implanted with expression, and progesterone production, with an IDso of 0.2 diethylstilbestrol capsules (2 cm) at 21 days of age and nM. -
Creating an Artificial 3-Dimensional Ovarian Follicle Culture System
micromachines Article Creating an Artificial 3-Dimensional Ovarian Follicle Culture System Using a Microfluidic System Mae W. Healy 1,2, Shelley N. Dolitsky 1, Maria Villancio-Wolter 3, Meera Raghavan 3, Alexandra R. Tillman 3 , Nicole Y. Morgan 3, Alan H. DeCherney 1, Solji Park 1,*,† and Erin F. Wolff 1,4,† 1 Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (M.W.H.); [email protected] (S.N.D.); [email protected] (A.H.D.); [email protected] (E.F.W.) 2 Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA 3 Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (M.V.-W.); [email protected] (M.R.); [email protected] (A.R.T.); [email protected] (N.Y.M.) 4 Pelex, Inc., McLean, VA 22101, USA * Correspondence: [email protected] † Solji Park and Erin F. Wolff are co-senior authors. Abstract: We hypothesized that the creation of a 3-dimensional ovarian follicle, with embedded gran- ulosa and theca cells, would better mimic the environment necessary to support early oocytes, both structurally and hormonally. Using a microfluidic system with controlled flow rates, 3-dimensional Citation: Healy, M.W.; Dolitsky, S.N.; two-layer (core and shell) capsules were created. The core consists of murine granulosa cells in Villancio-Wolter, M.; Raghavan, M.; 0.8 mg/mL collagen + 0.05% alginate, while the shell is composed of murine theca cells suspended Tillman, A.R.; Morgan, N.Y.; in 2% alginate. -
Oogenesis [PDF]
Oogenesis Dr Navneet Kumar Professor (Anatomy) K.G.M.U Dr NavneetKumar Professor Anatomy KGMU Lko Oogenesis • Development of ovum (oogenesis) • Maturation of follicle • Fate of ovum and follicle Dr NavneetKumar Professor Anatomy KGMU Lko Dr NavneetKumar Professor Anatomy KGMU Lko Oogenesis • Site – ovary • Duration – 7th week of embryo –primordial germ cells • -3rd month of fetus –oogonium • - two million primary oocyte • -7th month of fetus primary oocyte +primary follicle • - at birth primary oocyte with prophase of • 1st meiotic division • - 40 thousand primary oocyte in adult ovary • - 500 primary oocyte attain maturity • - oogenesis completed after fertilization Dr Navneet Kumar Dr NavneetKumar Professor Professor (Anatomy) Anatomy KGMU Lko K.G.M.U Development of ovum Oogonium(44XX) -In fetal ovary Primary oocyte (44XX) arrest till puberty in prophase of 1st phase meiotic division Secondary oocyte(22X)+Polar body(22X) 1st phase meiotic division completed at ovulation &enter in 2nd phase Ovum(22X)+polarbody(22X) After fertilization Dr NavneetKumar Professor Anatomy KGMU Lko Dr NavneetKumar Professor Anatomy KGMU Lko Dr Navneet Kumar Dr ProfessorNavneetKumar (Anatomy) Professor K.G.M.UAnatomy KGMU Lko Dr NavneetKumar Professor Anatomy KGMU Lko Maturation of follicle Dr NavneetKumar Professor Anatomy KGMU Lko Maturation of follicle Primordial follicle -Follicular cells Primary follicle -Zona pallucida -Granulosa cells Secondary follicle Antrum developed Ovarian /Graafian follicle - Theca interna &externa -Membrana granulosa -Antrial -
Role of FSH in Regulating Granulosa Cell Division and Follicular Atresia in Rats J
Role of FSH in regulating granulosa cell division and follicular atresia in rats J. J. Peluso and R. W. Steger Reproductive Physiology Laboratories, C. S. Moti Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan 48201, U.S.A. Summary. The effects of PMSG on the mitotic activity of granulosa cells and atresia of large follicles in 24-day-old rats were examined. The results showed that the labelling index (1) decreased in atretic follicles parallel with a loss of FSH binding, and (2) in- creased in hypophysectomized rats treated with FSH. It is concluded that FSH stimu- lates granulosa cell divisions and that atresia may be caused by reduced binding of FSH to the granulosa cells. Introduction Granulosa cells of primary follicles undergo repeated cell divisions and thus result in the growth of the follicle (Pederson, 1972). These divisions are stimulated by FSH and oestrogen, but FSH is also necessary for antrum formation (Goldenberg, Vaitukaitus & Ross, 1972). The stimulatory effects of FSH on granulosa cell divisions may be mediated through an accelerated oestrogen synthesis because FSH induces aromatizing enzymes and enhances oestrogen synthesis within the granulosa cells (Dorrington, Moon & Armstrong, 1975; Armstrong & Papkoff, 1976). Although many follicles advance beyond the primordial stage, most undergo atresia (Weir & Rowlands, 1977). Atretic follicles are characterized by a low mitotic activity, pycnotic nuclei, and acid phosphatase activity within the granulosa cell layer (Greenwald, 1974). The atresia of antral follicles occurs in three consecutive stages (Byskov, 1974). In Stage I, there is a slight reduction in the frequency of granulosa cell divisions and pycnotic nuclei appear. -
Diagnostic Evaluation of the Infertile Female: a Committee Opinion
Diagnostic evaluation of the infertile female: a committee opinion Practice Committee of the American Society for Reproductive Medicine American Society for Reproductive Medicine, Birmingham, Alabama Diagnostic evaluation for infertility in women should be conducted in a systematic, expeditious, and cost-effective manner to identify all relevant factors with initial emphasis on the least invasive methods for detection of the most common causes of infertility. The purpose of this committee opinion is to provide a critical review of the current methods and procedures for the evaluation of the infertile female, and it replaces the document of the same name, last published in 2012 (Fertil Steril 2012;98:302–7). (Fertil SterilÒ 2015;103:e44–50. Ó2015 by American Society for Reproductive Medicine.) Key Words: Infertility, oocyte, ovarian reserve, unexplained, conception Use your smartphone to scan this QR code Earn online CME credit related to this document at www.asrm.org/elearn and connect to the discussion forum for Discuss: You can discuss this article with its authors and with other ASRM members at http:// this article now.* fertstertforum.com/asrmpraccom-diagnostic-evaluation-infertile-female/ * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace. diagnostic evaluation for infer- of the male partner are described in a Pregnancy history (gravidity, parity, tility is indicated for women separate document (5). Women who pregnancy outcome, and associated A who fail to achieve a successful are planning to attempt pregnancy via complications) pregnancy after 12 months or more of insemination with sperm from a known Previous methods of contraception regular unprotected intercourse (1). -
A Four-Year-Old Girl with Ovarian Tumor Presented with Precocious Pseudo Puberty
Journal of Diabetes, Metabolic Disorders & Control Case Report Open Access A four-year-old girl with ovarian tumor presented with precocious pseudo puberty Abstract Volume 3 Issue 5 - 2016 Precocious puberty in girls is generally defined as appearance of secondary sexual Majed Alhabib,1 Alsaleh Yassin,2 Mallick characteristics before eight years of age. Precocious puberty is divided into central 3 1 precocious puberty and precocious pseudo puberty (peripheral).1 Central precocious Mohammed, Alsaheel Abdulhameed 1Pediatric Endocrinology Consultant, Children’s Specialized puberty (gonadotropin-dependent), which involves the premature activation of Hospital, King Fahad Medical City, Saudi Arabia hypothalamic-pituitary-gonadal axis. Precocious pseudo puberty (gonadotropin- 2Pediatric Endocrine Fellow, Children’s Specialized Hospital, King independent) is caused by activity of sex steroid hormones independently from the Fahad Medical City, Saudi Arabia activation of pituitary-gonadotropin axis.1 The commonest cause for precocious 3Pediatric Surgery Consultant, Children’s Specialized Hospital, pseudo puberty is functional ovarian cyst. Ovarian masses are generally considered King Fahad Medical City, Saudi Arabia rare in the premenarchal age group.2 Ovarian tumors of premenarchal girls generally originate from the germ cell line.2 The most common presentation of these tumors in Correspondence: Majed Alhabib, King Fahad Medical City, children is precocious pseudo puberty.3 In This report we describe a 4year-old girl Saudi Arabia, Tel +966 505 -
Effects of Insulin and Luteinizing Hormone on Ovarian Granulosa Cell Aromatase Activity In
Effects of Insulin and Luteinizing Hormone on Ovarian Granulosa Cell Aromatase Activity in 1998 Animal Science Cattle Research Report Pages 223-226 Authors: Story in Brief The direct effect of insulin and luteinizing hormone (LH) on ovarian granulosa cell function in L.J. Spicer cattle was evaluated by using a serum-free culture system. Granulosa cells were obtained from large (³ 8 mm) follicles collected from cattle and cultured for 4 d. During the last 2 d of culture, cells were exposed to testosterone in serum-free medium to assess aromatase activity. Culture medium was collected for quantification of estradiol, and cell numbers were determined. Insulin significantly increased estradiol production after 1 and 2 d of treatment. Alone, LH had no effect on estradiol production. However, 30 ng/mL of LH reduced the stimulatory effect of insulin on estradiol production after 1 d but not 2 d of treatment. (Key Words: Insulin, Luteinizing Hormone, Granulosa Cells, Estradiol, Cattle.) Introduction Increased secretion of estradiol by growing dominant ovulatory and non-ovulatory follicles is a critical step during the estrous cycle that leads to the expression of estrus, release of an ovulatory surge of LH, ovulation of the follicle and release of the oocyte (Spicer and Echternkamp, 1986; Ginther et al., 1997). However, the hormonal factors that regulate production of estradiol by the dominant follicle in cattle are not completely understood. Estradiol is produced by bovine granulosa cells via the action of aromatase which is a granulosa- cell specific enzyme that converts androgens (e.g., testosterone) into estrogens (e.g., estradiol). Previous studies have shown that insulin is a potent stimulator of aromatase activity in cattle (Spicer et al., 1994) but direct effects of LH on aromatase activity have not been reported for cattle. -
High Levels of Luteinizing Hormone Analog Stimulate Gonadal
Oncogene (2003) 22, 3269–3278 & 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00 www.nature.com/onc High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-a-subunit promoter/ Simian virus 40 T-antigen fusion gene Maarit Mikola1, Jukka Kero2, John H Nilson3, Ruth A Keri3, Matti Poutanen1 and Ilpo Huhtaniemi*,1 1Department of Physiology, University of Turku, FIN-20520 Turku, Finland; 2Department of Pediatrics, University of Turku, FIN-20520 Turku, Finland; 3Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA Transgenic (TG) mice expressing the Simian virus 40 are involved in the appearance and/or maintenance of T-antigen under the control of the murine inhibin-a gonadal tumors. Among human gonadal malignancies, promoter (Inha/Tag) develop granulosa and Leydig cell ovarian tumors are the commonest, with the poorest tumors at the age of 5–6 months, with 100% penetrance. prognosis. In attempts to improve the diagnostics and When these mice are gonadectomized, they develop treatment of ovarian cancers, it is essential to learn more adrenocortical tumors. Suppression of gonadotropin about their pathogenesis, including the regulation of secretion inhibits the tumorigenesis in the gonads of intact their aggressive growth and invasion, and to develop animals and in the adrenals after gonadectomy. To study better predictive markers. It has often been suggested further the role of luteinizing hormone (LH) in gonadal that LH could promote the development of certain types and adrenal tumorigenesis, a double TG mouse model was of ovarian and testicular cancer. -
The Reproductive System
PowerPoint® Lecture Slides prepared by Meg Flemming Austin Community College C H A P T E R 19 The Reproductive System © 2013 Pearson Education, Inc. Chapter 19 Learning Outcomes • 19-1 • List the basic components of the human reproductive system, and summarize the functions of each. • 19-2 • Describe the components of the male reproductive system; list the roles of the reproductive tract and accessory glands in producing spermatozoa; describe the composition of semen; and summarize the hormonal mechanisms that regulate male reproductive function. • 19-3 • Describe the components of the female reproductive system; explain the process of oogenesis in the ovary; discuss the ovarian and uterine cycles; and summarize the events of the female reproductive cycle. © 2013 Pearson Education, Inc. Chapter 19 Learning Outcomes • 19-4 • Discuss the physiology of sexual intercourse in males and females. • 19-5 • Describe the age-related changes that occur in the reproductive system. • 19-6 • Give examples of interactions between the reproductive system and each of the other organ systems. © 2013 Pearson Education, Inc. Basic Reproductive Structures (19-1) • Gonads • Testes in males • Ovaries in females • Ducts • Accessory glands • External genitalia © 2013 Pearson Education, Inc. Gametes (19-1) • Reproductive cells • Spermatozoa (or sperm) in males • Combine with secretions of accessory glands to form semen • Oocyte in females • An immature gamete • When fertilized by sperm becomes an ovum © 2013 Pearson Education, Inc. Checkpoint (19-1) 1. Define gamete. 2. List the basic components of the reproductive system. 3. Define gonads. © 2013 Pearson Education, Inc. The Scrotum (19-2) • Location of primary male sex organs, the testes • Hang outside of pelvic cavity • Contains two chambers, the scrotal cavities • Wall • Dartos, a thin smooth muscle layer, wrinkles the scrotal surface • Cremaster muscle, a skeletal muscle, pulls testes closer to body to ensure proper temperature for sperm © 2013 Pearson Education, Inc. -
Reproductive Cycles in Females
MOJ Women’s Health Review Article Open Access Reproductive cycles in females Abstract Volume 2 Issue 2 - 2016 The reproductive system in females consists of the ovaries, uterine tubes, uterus, Heshmat SW Haroun vagina and external genitalia. Periodic changes occur, nearly every one month, in Faculty of Medicine, Cairo University, Egypt the ovary and uterus of a fertile female. The ovarian cycle consists of three phases: follicular (preovulatory) phase, ovulation, and luteal (postovulatory) phase, whereas Correspondence: Heshmat SW Haroun, Professor of the uterine cycle is divided into menstruation, proliferative (postmenstrual) phase Anatomy and Embryology, Faculty of Medicine, Cairo University, and secretory (premenstrual) phase. The secretory phase of the endometrium shows Egypt, Email [email protected] thick columnar epithelium, corkscrew endometrial glands and long spiral arteries; it is under the influence of progesterone secreted by the corpus luteum in the ovary, and is Received: June 30, 2016 | Published: July 21, 2016 an indicator that ovulation has occurred. Keywords: ovarian cycle, ovulation, menstrual cycle, menstruation, endometrial secretory phase Introduction lining and it contains the uterine glands. The myometrium is formed of many smooth muscle fibres arranged in different directions. The The fertile period of a female extends from the age of puberty perimetrium is the peritoneal covering of the uterus. (11-14years) to the age of menopause (40-45years). A fertile female exhibits two periodic cycles: the ovarian cycle, which occurs in The vagina the cortex of the ovary and the menstrual cycle that happens in the It is the birth and copulatory canal. Its anterior wall measures endometrium of the uterus. -
Inhibin/Activin and Ovarian Cancer
Endocrine-Related Cancer (2004) 11 35–49 REVIEW Inhibin/activin and ovarian cancer D M Robertson, H G Burger and P J Fuller Prince Henry’s Institute of Medical Research, PO 5152, Clayton, Victoria 3168, Australia (Correspondence should be addressed to D M Robertson; Email: [email protected]) Abstract Inhibin and activin are members of the transforming growth factor beta (TGFb) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, a and either bAorbB (inhibin A and B). Activins are hetero- or homodimers of the b-subunits. Inhibin and free a subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin a subunit gene deletion develop stromal/granulosa cell tumours suggesting that the a subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFb superfamily is also discussed. Endocrine-Related Cancer (2004) 11 35–49 Introduction Inhibin and activin In contrast to other gynaecological cancers, little progress Structure has been made over the past decades in improving the life Inhibin and activin are members of the transforming expectancy of women with ovarian cancer. -
The Key Signaling Cascades in Granulosa Cells During Follicular Development and Ovulation Process
J. Mamm. Ova Res. Vol. 28, 25–31, 2011 25 —Mini Review— The Key Signaling Cascades in Granulosa Cells during Follicular Development and Ovulation Process Masayuki Shimada1* and Yasuhisa Yamashita2 1Laboratory of Reproductive Endocrinology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan 2Laboratory of Animal Physiology, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023, Japan Abstract: Follicular development and ovulation process Introduction are complex events in which a sequential process is started by two pituitary hormones, FSH and LH. Recent Follicle stimulating hormone (FSH) secreted from the studies using microarray analysis have shown that pituitary gland acts on granulosa cells in follicles at the numerous endocrine factors are expressed and secondary and small antral stages to direct and ensure specifically activate the signal transduction cascades to the development of preovulatory follicles [1]. In FSH- upregulate or downregulate the expression of target stimulated granulosa cells, Ccnd2 mRNA is expressed genes in granulosa cells and cumulus cells. Especially, and its translated product (Cyclin D2) binds to cyclin the PI 3-kinase-AKT pathway during the follicular dependent kinase 4 (CDK4), inducing cell proliferation. development stage and the ERK1/2 pathway after LH FSH also increases estradiol 17 (E2) production that is surge are essential for initiating the dramatic changes in converted from androgens via induction of the enzyme follicular function. The proliferation of granulosa cells and aromatase [1–3]. E2 acts on ESR2 (estrogen receptor cell survival are dependent on the FSH-induced PI 3- beta; ER) that is expressed in granulosa cells, and kinase-AKT pathway in a c-Src-EGFR dependent enhances FSH-mediated granulosa cell proliferation manner.