DOCSLIB.ORG

Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility Physiol Rev 96: 55–97, 2016 Published November 18, 2015; doi:10.1152/physrev.00017.2015 MALE REPRODUCTIVE DISORDERS AND FERTILITY TRENDS: INFLUENCES OF ENVIRONMENT AND GENETIC SUSCEPTIBILITY Niels E. Skakkebaek, Ewa Rajpert-De Meyts, Germaine M. Buck Louis, Jorma Toppari, Anna-Maria Andersson, Michael L. Eisenberg, Tina Kold Jensen, Niels Jørgensen, Shanna H. Swan, Katherine J. Sapra, Søren Ziebe, Lærke Priskorn, and Anders Juul Department of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson A-M, Eisenberg ML, Jensen TK, Jørgensen N, Swan SH, Sapra KJ, Ziebe S, Priskorn L, Juul A. Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility. Physiol Rev 96: 55–97, 2016. Published November 18, 2015; doi:10.1152/physrev.00017.2015.—It is predicted that LJapan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental expo- sures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in repro- ductive physiology and pathophysiology, particularly in highly industrialized countries facing decreas- ing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography. I. INTRODUCTION 55 woman) far below 2.1, which is the rate considered neces- II. INCIDENCE TRENDS, GENETIC... 56 sary to sustain a population size at current numbers. At the III. INFERTILITY 73 same time a spectacular rise in testicular germ cell cancer IV. ROLE OF GENETIC BACKGROUND FOR THE... 76 (TGCC) has occurred in all parts of the World. In addition, V. ENVIRONMENTAL MODULATION OF... 78 other male reproductive problems, of which several are VI. POSSIBLE ROLE OF MALE... 80 linked to testicular cancer, including disorders of spermato- VII. AFTERWORD: RESEARCH CHALLENGES 83 genesis, are widespread and have recently been the focus for many basic and clinical research projects. I. INTRODUCTION As shown in FIGURE 1, the total fertility rate has fallen significantly in European Union (EU), Japan, and the United During the 20th century, populations of industrialized States (US). Also, Hong Kong and Singapore have for de- countries all over the world have experienced a decline in cades had TFR significantly below replacement level (now total fertility rates (TFR, average number of live births per between 1.0 and 1.5). Fertility has therefore become a sig- 0031-9333/16 Copyright © 2016 the American Physiological Society 55 SKAKKEBAEK ET AL. 4 fecundity is difficult. Fecundity depends not only on a num- European Union ber of physiological and pathophysiological factors in both Japan partners of a couple. Studies on rates of conceptions are also 3.5 USA confounded by social, economic, and psychological factors Replacement level that might change over time. In addition, TFR can be a poor marker of fecundity as it can be skewed by multiple factors, 3 including induced abortion rates, availability of contracep- tion, desire for pregnancy, and access to assisted reproduc- 2.5 tion, for example, before 1990 several Eastern European countries had higher abortion rates than birth rates. Total pregnancy rate, which includes both live births and induced 2 abortions, might be more informative of changes in fecun- dity in a population than TFR (230). 1.5 The aim of this review is to analyze some global trends in male reproductive health problems and their potential ef- Total Fertility Rate (per woman) 1 fects on male fecundity as well as the possible etiological roles of environmental, epigenetic, and genetic factors for these trends. Besides testicular cancer, we shall review re- 0.5 cent studies on infertility, semen quality, cryptorchidism, and hypospadias and how these disorders might be interre- lated with testicular cancer and with each other, through a 0 testicular dysgenesis syndrome (TDS) (FIGURE 3). We shall 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 also review trends in sex ratio and the potential roles of FIGURE 1. Total Fertility Rates (TFR), European Union, Japan and male reproductive disorders for couple fecundity and fertil- United States, 1960–2013. Dotted line represents a fertility rate of ity rates. Finally, we will present some urgent research needs 2.1, below which a population cannot be sustained. From the World within the field of physiology and pathophysiology of male Bank: http://databank.worldbank.org/data/views/variableselection/ reproduction. selectvariables.aspx?sourceϭworld-development-indicators. II. INCIDENCE TRENDS, GENETIC nificant political theme (122). Social and economic factors SUSCEPTIBILITY, AND PATHOGENESIS combined with the advent of effective contraceptive meth- OF REPRODUCTIVE DISORDERS ods and access to induced abortions have contributed sub- stantially to decreasing TFR, although the decline in birth rate started decades before the contraceptive pill and legal A. Testicular Germ Cell Cancer abortion were introduced (FIGURE 2). The strongest evidence for adverse trends in male reproduc- Surprisingly little is known about biological factors that tive health comes from epidemiological studies of TGCC, might have changed human fecundity (capacity to conceive) including both seminoma and nonseminoma (231, 481). and thereby influenced the TFR. The lack of knowledge in The increase was first noted in developed countries, where this area probably reflects the fact that research into human incidence rates have been highest in countries with North- 4.5 4 3.5 3 FIGURE 2. Total Fertility Rate (TFR), Denmark 1901–2014. From Statistics Denmark: http://www. 2.5 statistikbanken.dk/statbank5a/default.asp?wϭ1600. Dot- ted line represents a fertility rate of 2.1. Note that a 2 downwards trend in TFR started long before introduc- 1.5 tion of the contraceptive pill in the 1960s. Apparently the trend was interrupted by the First and Second World 1 Wars. Total fertility rate (per woman) 0.5 0 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 56 Physiol Rev • VOL 96 • JANUARY 2016 • www.prv.org FERTILITY TRENDS, ENVIRONMENT, AND GENETICS Fetal germ cells Fetal Leydig cells Environmental Lifestyle exposure factors Sertoli cells Genetic defects and Epigenetic polymorphisms factors Testicular dysgenesis FIGURE 3. The hypothesis of testicular dys- genesis syndrome (TDS) and signs that might Decreased Leydig cell function Disturbed Sertoli cell function be linked to it: poor spermatogenesis, testic- ular cancer, hypospadias, cryptorchidism, and short ano-genital distance (AGD). The sin- gle symptoms and combinations thereof are Decreased INSL3 Decreased Impaired germ cell production testosterone production differentiation risk factors for reduced fecundity. [Updated from Skakkebaek et al. (387).] Hypospadias Short AGD Cryptorchidism Decreased Impaired GCNIS testosterone production spermatogenesis Testicular cancer Reduced male fecundity influencing pregnancy rates ern European ancestry, including Denmark, Norway, and ular germ cell neoplasia in situ (GCNIS) and malignant New Zealand (341). In the US, the highest incidences have TGCC, except somatically differentiated nonseminomas been found among descendants of Europeans in the Mid- (347, 402). The significance of KIT/KITLG pathway for the and North West (269). Interestingly, recent studies have TGCC risk, both in the sporadic and familial cases, has shown that countries with previously low rates of TGCC, been confirmed by subsequent studies in different popula- such as Finland, Italy, and Spain, are now catching up (FIG- tions, and by associations with genes functionally linked to URE 4),
Load more

Recommended publications
  • Infertility Diagnosis and Treatment
    UnitedHealthcare® Oxford Clinical Policy Infertility Diagnosis and Treatment Policy Number: INFERTILITY 008.12 T2 Effective Date: July 1, 2021 Instructions for Use Table of Contents Page Related Policies Coverage Rationale ....................................................................... 1 • Follicle Stimulating Hormone (FSH) Gonadotropins Documentation Requirements ...................................................... 2 • Human Menopausal Gonadotropins (hMG) Definitions ...................................................................................... 3 • Preimplantation Genetic Testing Prior Authorization Requirements ................................................ 3 Applicable Codes .......................................................................... 3 Related Optum Clinical Guideline Description of Services ................................................................. 3 • Fertility Solutions Medical Necessity Clinical Benefit Considerations .................................................................. 7 Guideline: Infertility Clinical Evidence ........................................................................... 8 U.S. Food and Drug Administration ........................................... 14 References ................................................................................... 15 Policy History/Revision Information ........................................... 18 Instructions for Use ..................................................................... 18 Coverage Rationale See Benefit Considerations
    [Show full text]
  • Human Physiology/The Male Reproductive System 1 Human Physiology/The Male Reproductive System
    Human Physiology/The male reproductive system 1 Human Physiology/The male reproductive system ← The endocrine system — Human Physiology — The female reproductive system → Homeostasis — Cells — Integumentary — Nervous — Senses — Muscular — Blood — Cardiovascular — Immune — Urinary — Respiratory — Gastrointestinal — Nutrition — Endocrine — Reproduction (male) — Reproduction (female) — Pregnancy — Genetics — Development — Answers Introduction In simple terms, reproduction is the process by which organisms create descendants. This miracle is a characteristic that all living things have in common and sets them apart from nonliving things. But even though the reproductive system is essential to keeping a species alive, it is not essential to keeping an individual alive. In human reproduction, two kinds of sex cells or gametes are involved. Sperm, the male gamete, and an egg or ovum, the female gamete must meet in the female reproductive system to create a new individual. For reproduction to occur, both the female and male reproductive systems are essential. While both the female and male reproductive systems are involved with producing, nourishing and transporting either the egg or sperm, they are different in shape and structure. The male has reproductive organs, or genitals, that are both inside and outside the pelvis, while the female has reproductive organs entirely within the pelvis. The male reproductive system consists of the testes and a series of ducts and glands. Sperm are produced in the testes and are transported through the reproductive ducts. These ducts include the epididymis, ductus deferens, ejaculatory duct and urethra. The reproductive glands produce secretions that become part of semen, the fluid that is ejaculated from the urethra. These glands include the seminal vesicles, prostate gland, and bulbourethral glands.
    [Show full text]
  • Recurrent Miscarriage
    Elizabeth Taylor, MD, FRCSC, Mohammed Bedaiwy, MD, PhD, Mahmoud Iwes, MD Recurrent miscarriage Management of pregnancy loss includes investigating causes, addressing modifiable risk factors, and providing supportive care in the first trimester of pregnancy. ABSTRACT: Early miscarriages are arly miscarriage has been re­ Genetic causes those occurring within the first 12 ported to occur in 17% to 31% The risk of miscarriage increases completed weeks of gestation. Re- E of pregnancies,1,2 and is de­ with maternal age. At age 20 to 24 current miscarriage, defined as two fined as a nonviable intrauterine the risk is approximately 10%, with or more consecutive pregnancy loss- pregnancy with either an empty ges­ risk increasing to nearly 80% by age es, affects 3% of couples trying to tational sac or a gestational sac con­ 45.5 The relationship between mis­ conceive and can cause consider- taining an embryo or fetus without carriage risk and maternal age can be able distress. The risk of miscarriage fetal heart activity within the first explained by the increasing rate of oo­ increases with maternal age. Genet- 12 completed weeks of gestation.3 cyte aneuploidy that occurs as women ic abnormalities, uterine anomalies, Recurrent miscarriage occurs in 3% grow older. In one study, oocytes and endocrine dysfunction can all of couples trying to conceive. The examined during in vitro fertilization lead to miscarriage. Other causes of American Society for Reproductive (IVF) treatment had only a 10% risk miscarriage are autoimmune disor- Medicine (ASRM) defines recurrent of being aneuploid in women younger ders such as antiphospholipid syn- miscarriage as two or more failed than age 35, but by age 43 the risk of drome and chronic endometritis.
    [Show full text]
  • Male Infertility and Risk of Nonmalignant Chronic Diseases: a Systematic Review of the Epidemiological Evidence
    282 Male Infertility and Risk of Nonmalignant Chronic Diseases: A Systematic Review of the Epidemiological Evidence Clara Helene Glazer, MD1 Jens Peter Bonde, MD, DMSc, PhD1 Michael L. Eisenberg, MD2 Aleksander Giwercman, MD, DMSc, PhD3 Katia Keglberg Hærvig, MSc1 Susie Rimborg4 Ditte Vassard, MSc5 Anja Pinborg, MD, DMSc, PhD6 Lone Schmidt, MD, DMSc, PhD5 Elvira Vaclavik Bräuner, PhD1,7 1 Department of Occupational and Environmental Medicine, Address for correspondence Clara Helene Glazer, MD, Department of Bispebjerg University Hospital, Copenhagen NV, Denmark Occupational and Environmental Medicine, Bispebjerg University 2 Departments of Urology and Obstetrics/Gynecology, Stanford Hospital, Copenhagen NV, Denmark University School of Medicine, Stanford, California (e-mail: [email protected]). 3 Department of Translational Medicine, Molecular Reproductive Medicine, Lund University, Lund, Sweden 4 Faculty Library of Natural and Health Sciences, University of Copenhagen, Copenhagen K, Denmark 5 Department of Public Health, University of Copenhagen, Copenhagen, Denmark 6 Department of Obstetrics/Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark 7 Mental Health Center Ballerup, Ballerup, Denmark Semin Reprod Med 2017;35:282–290 Abstract The association between male infertility and increased risk of certain cancers is well studied. Less is known about the long-term risk of nonmalignant diseases in men with decreased fertility. A systemic literature review was performed on the epidemiologic evidence of male infertility as a precursor for increased risk of diabetes, cardiovascular diseases, and all-cause mortality. PubMed and Embase were searched from January 1, 1980, to September 1, 2016, to identify epidemiological studies reporting associations between male infertility and the outcomes of interest. Animal studies, case reports, reviews, studies not providing an accurate reference group, and studies including Downloaded by: Stanford University.
    [Show full text]
  • Coupling of the HPA and HPG Axes
    University of New Orleans ScholarWorks@UNO University of New Orleans Theses and Dissertations Dissertations and Theses Fall 12-20-2013 Coupling of the HPA and HPG Axes Andrew Dismukes University of New Orleans, [email protected] Follow this and additional works at: https://scholarworks.uno.edu/td Part of the Biological Psychology Commons Recommended Citation Dismukes, Andrew, "Coupling of the HPA and HPG Axes" (2013). University of New Orleans Theses and Dissertations. 1732. https://scholarworks.uno.edu/td/1732 This Thesis is protected by copyright and/or related rights. It has been brought to you by ScholarWorks@UNO with permission from the rights-holder(s). You are free to use this Thesis in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights- holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/or on the work itself. This Thesis has been accepted for inclusion in University of New Orleans Theses and Dissertations by an authorized administrator of ScholarWorks@UNO. For more information, please contact [email protected]. Coupling of the HPA and HPG Axes A Thesis Submitted to the Graduate Faculty of the University of New Orleans in partial fulfillment of the requirements for the degree of Master of Science in Psychology by Andrew Dismukes B.S. Auburn University December, 2013 Table of Contents Table of Figures ...........................................................................................................................................................
    [Show full text]
  • 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).
    [Show full text]
  • Human Reproduction: Clinical, Pathologic and Pharmacologic Correlations
    HUMAN REPRODUCTION: CLINICAL, PATHOLOGIC AND PHARMACOLOGIC CORRELATIONS 2008 Course Co-Director Kirtly Parker Jones, M.D. Professor Vice Chair for Educational Affairs Department of Obstetrics and Gynecology Course Co-Director C. Matthew Peterson, M.D. Professor and Chair Department of Obstetrics and Gynecology 1 Welcome to the course on Human Reproduction. This syllabus has been recently revised to incorporate the most recent information available and to insure success on national qualifying examinations. This course is designed to be used in conjunction with our website which has interactive materials, visual displays and practice tests to assist your endeavors to master the material. Group discussions are provided to allow in-depth coverage. We encourage you to attend these sessions. For those of you who are web learners, please visit our web site that has case studies, clinical/pathological correlations, and test questions. http://libarary.med.utah.edu/kw/human_reprod 2 TABLE OF CONTENTS Page Lectures/Examination................................................................................................................................... 5 Schedule........................................................................................................................................................ 6 Faculty .......................................................................................................................................................... 9 Groups, Workshop.....................................................................................................................................
    [Show full text]
  • Review Article Physiologic Course of Female Reproductive Function: a Molecular Look Into the Prologue of Life
    Hindawi Publishing Corporation Journal of Pregnancy Volume 2015, Article ID 715735, 21 pages http://dx.doi.org/10.1155/2015/715735 Review Article Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life Joselyn Rojas, Mervin Chávez-Castillo, Luis Carlos Olivar, María Calvo, José Mejías, Milagros Rojas, Jessenia Morillo, and Valmore Bermúdez Endocrine-Metabolic Research Center, “Dr. Felix´ Gomez”,´ Faculty of Medicine, University of Zulia, Maracaibo 4004, Zulia, Venezuela Correspondence should be addressed to Joselyn Rojas; [email protected] Received 6 September 2015; Accepted 29 October 2015 Academic Editor: Sam Mesiano Copyright © 2015 Joselyn Rojas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The genetic, endocrine, and metabolic mechanisms underlying female reproduction are numerous and sophisticated, displaying complex functional evolution throughout a woman’s lifetime. This vital course may be systematized in three subsequent stages: prenatal development of ovaries and germ cells up until in utero arrest of follicular growth and the ensuing interim suspension of gonadal function; onset of reproductive maturity through puberty, with reinitiation of both gonadal and adrenal activity; and adult functionality of the ovarian cycle which permits ovulation, a key event in female fertility, and dictates concurrent modifications in the endometrium and other ovarian hormone-sensitive tissues. Indeed, the ultimate goal of this physiologic progression is to achieve ovulation and offer an adequate environment for the installation of gestation, the consummation of female fertility. Strict regulation of these processes is important, as disruptions at any point in this evolution may equate a myriad of endocrine- metabolic disturbances for women and adverse consequences on offspring both during pregnancy and postpartum.
    [Show full text]
  • Age and Fertility: a Guide for Patients
    Age and Fertility A Guide for Patients PATIENT INFORMATION SERIES Published by the American Society for Reproductive Medicine under the direction of the Patient Education Committee and the Publications Committee. No portion herein may be reproduced in any form without written permission. This booklet is in no way intended to replace, dictate or fully define evaluation and treatment by a qualified physician. It is intended solely as an aid for patients seeking general information on issues in reproductive medicine. Copyright © 2012 by the American Society for Reproductive Medicine AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Age and Fertility A Guide for Patients Revised 2012 A glossary of italicized words is located at the end of this booklet. INTRODUCTION Fertility changes with age. Both males and females become fertile in their teens following puberty. For girls, the beginning of their reproductive years is marked by the onset of ovulation and menstruation. It is commonly understood that after menopause women are no longer able to become pregnant. Generally, reproductive potential decreases as women get older, and fertility can be expected to end 5 to 10 years before menopause. In today’s society, age-related infertility is becoming more common because, for a variety of reasons, many women wait until their 30s to begin their families. Even though women today are healthier and taking better care of themselves than ever before, improved health in later life does not offset the natural age-related decline in fertility. It is important to understand that fertility declines as a woman ages due to the normal age- related decrease in the number of eggs that remain in her ovaries.
    [Show full text]
  • World-Renowned Expert in Infertility Presents Findings to European
    World-Renowned Expert in Infertility Presents Findings to European Conference After Two Recurrent Miscarriages, Patients Should be Thoroughly Evaluated for Risk Factors Dr. William Kutteh, M.D., one of the world’s leading researchers in recurrent pregnancy loss (RPL), was invited to present his latest discoveries to theEuropean Society of Human Reproduction and Embryology (ESHRE). Dr. Kutteh’s research on recurrent pregnancy loss calls for early intervention after the second miscarriage, a change in how physicians currently treat the condition. RPL is defined as three or more consecutive miscarriages that occur before the 20th week of pregnancy. In the general population, miscarriage occurs in 20 percent of all pregnancies, but recurrent miscarriage occurs in only 5 percent of all women seeking pregnancy. Dr. Kutteh’s study, the largest of its kind on recurrent miscarriage, scientifically proved what many physicians intrinsically knew. The 2010 study, published in Fertility and Sterility-- Diagnostic Factors Identified in 1020 Women with Two Versus Three or More Recurrent Pregnancy Losses--found that even after only two pregnancy losses, a definitive cause for RPL could be determined in two-thirds of patients in the study. Dr. Kutteh’s research showed that there was no statistical difference in women with RPL who had two pregnancy losses, and those who had three or more losses, proving that earlier intervention was appropriate. Patients with RPL are now encouraged to begin testing for known risk factors for infertility after the second miscarriage. Determining Risk Factors for Recurrent Miscarriage Recurrent miscarriage causes include anatomic, hormonal, autoimmune, infectious, genetic, or hematologic issues. Expeditiously determining the causes of miscarriage can lead to more targeted treatment, and for 67 percent of patients, a successful full-term pregnancy.
    [Show full text]
  • Reproductive Physiology and Endocrinology
    Comparative Veterinary Reproduction and Obstetrics, Instructor: Patrick J. Hemming DVM LECTURE 3 Reproductive Physiology and Endocrinology A. Reproductive endocrinology 1. Reproductive organs and hormones of the endocrine system; Endocrine control of estrus cycles, pregnancy, spermatogenesis, sexual development and behavior and all other aspects of reproduction is the responsibility of the hypothalamic-pituitary-gonadal axis. Hypothalamic hormones control the release of pituitary hormones while pituitary hormones exert their effects on the development, function and hormone synthesis of the gonads. Gonadal hormones, in addition to direct effects on the genital organs, complete the hypothalamic-pituitary-gonadal axis by either suppressing or stimulating the production and/or release of hypothalamic and pituitary hormones in what is called negative feedback or positive feedback mechanisms. Gonadal Hormones also exert influence over growth, behavior, organs or tissue function such as in the mammary glands. Most other endocrine systems have similar feedback mechanisms. A) Hypothalamus; the master endocrine gland; The hypothalamus represents the interface of the central nervous system with the endocrine system. The hypothalamus receives direct CNS innervation from several areas of the brain stem and cerebrum. Direct and indirect visual, olfactory, auditory and touch sensory inputs also innervate areas of the hypothalamus. Neurons of the hypothalamus involved with reproduction also contain receptors for estrogen and other steroidal hormones, constituting the feedback mechanism. These neuronal and hormonal signals regulate the endocrine functions of the hypothalamus. Anatomically the hypothalamus is a diffuse area of the brain, composed of groups of neurons organized into distinct nuclei. These nuclei lie dorsal and rostral of the pituitary gland and stalk, in an area surrounding the third ventricle, in the most rostral portions of the brain stem.
    [Show full text]
  • Anovulation and PCOS
    Anovulatory Infertility and PCOS ESHRE, Kiev 2010 Adam Balen MD, FRCOG Professor of Reproductive Medicine Leeds Teaching Hospitals, UK Disclosures: Medical advisor to Ferring, Organon SP Causes of Anovulatory Infertility Learning Objectives 1. To understand the causes of anovulation 2. Knowledge of the correct diagnostic tests 3. Effective assessment and diagnosis to plan appropriate ovulation induction therapy Hypothalamus GnRH Pituitary FSH LH Oestradiol, inhibins Progesterone……. LH FSH theca cells granulosa cells testosterone aromatase oestradiol oocytte Two cell – two gonadotrophin theory of oestrogen synthesis The Menstrual Cycle pmol/l 350 80 300 70 250 60 50 200 40 nmol/l 150 & 30 100 20 50 10 IU/L 0 0 0 2 4 6 8 10121416182022242628 E2 FSH LH P4 Causes of Anovulatory Infertility Group I: weight loss, systemic illness Hypothalamic/ Kallmann’s syndrome pituitary failure hypogonadotrophic hypogonadism Hyperprolactinaemia Hypopituitarism Group II: PCOS h/p dysfunction Group III: Premature ovarian failure (POF) Ovarian failure Resistant ovary syndrome (ROS) Causes of Anovulatory Infertility Group I: weight loss, systemic illness Hypothalamic/ Kallmann’s syndrome pituitary failure hypogonadotrophic hypogonadism Hyperprolactinaemia Hypopituitarism Group II: PCOS h/p dysfunction Group III: Premature ovarian failure (POF) Ovarian failure Resistant ovary syndrome (ROS) Causes of Anovulatory Infertility Group I: weight loss, systemic illness 5% Hypothalamic/ Kallmann’s syndrome pituitary failure hypogonadotrophic hypogonadism Hyperprolactinaemia Hypopituitarism Group II: PCOS 90% h/p dysfunction Group III: Premature ovarian failure (POF) 5% Ovarian failure Resistant ovary syndrome (ROS) Investigations 1. FSH, LH, oestradiol 2. Prolactin / TFTs 3. Testosterone (SHBG) 4. AMH...... 5. GTT, lipid profile 6. Ultrasound scan 7. Semen analysis 8.
    [Show full text]