Developmental exposure to environmental endocrine disruptors: Consequences within the ovary and on female reproductive function☆

Abstract

Female reproductive function depends upon the exquisite control of ovarian steroidogenesis that enables folliculogenesis, ovulation, and pregnancy. These mechanisms are set during fetal and/or neonatal development and undergo phases of differentiation throughout pre-and post-pubescent life. Ovarian development and function are collectively regulated by a host of endogenous growth factors, cytokines, gonadotropins, and steroid hormones as well as exogenous factors such as nutrients and environmental agents. Endocrine disruptors represent one class of environmental agent that can impact female fertility by altering ovarian development and function, purportedly through estrogenic, anti-estrogenic, and/or anti-androgenic effects. This review discusses ovarian development and function and how these processes are affected by some of the known estrogenic and anti-androgenic endocrine disruptors. Recent information suggests not only that exposure to endocrine disruptors during the developmental period causes reproductive abnormalities in adult life but also that these abnormalities are transgenerational. This latter finding adds another level of importance for identifying and understanding the mechanisms of action of these agents. 1-IntroductionThe primary function of an adult ovary is to produce the steroid and protein hormones needed to support (1) the development and maturation of ovarian follicles (i.e., folliculogenesis) including oocytes, (2) ovulation, and (3) the initiation and maintenance of pregnancy in mammals. In order for this to collectively occur, the secretion of ovarian hormones is tightly regulated by the neuroendocrine system and is locally controlled by many intraovarian feedback mechanisms (reviewed in [1]).Two major developmental events within the ovary are follicular assembly (i.e., the formation of primordial follicles) and the primordial-to-primary follicle transition (the "initial" recruitment) [1]. The initial phase of folliculogenesis is regulated by paracrine growth factors Correspondence: Dr. Mehmet Uzumcu, Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ Supported by NIH grant R21 ES013854-01A1 (MU) and funds from Robert Wood Johnson Medical School-UMDNJ (RZ).Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptReprod Toxicol. Author manuscript; available in PMC 2007 August 21. Published in final edited form as:Reprod Toxicol. 2007 ; 23(3): 337-352. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-...

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

“…This has previously been described by others for high doses of single chemicals (Armenti et al 2008, Adewale et al 2009). The process of follicle assembly and the recruitment of primordial follicles in the ovary to enter into growth are thought to be essential for the duration of the reproductive lifespan (Uzumcu & Zachow 2007, Crain et al 2008, Diamanti-Kandarakis et al 2009). Any chemical interfering with these processes may advance the onset of menopause.…”

Antiandrogen flutamide affects folliculogenesis during fetal development in pigs

“…Mammals are more susceptible to EDCs during fetal and neonatal life than in adulthood because of underdeveloped reproductive axes (Sweeney 2002). Environmental chemicals with androgenic and/or antiandrogenic activities are capable of interfering with androgen receptors (ARs) and regulate function of androgens within the endocrine system (Uzumcu & Zachow 2007).…”

Organochlorine compound levels in fertile and infertile women from Rio de Janeiro, Brazil

“…As female reproductive function depends upon ovarian steroidogenesis that enables folliculogen esis, ovulation, and pregnancy, the impact of altering ovarian development and function in female fertility may be the link between environmental exposure and reproductive failure (17).…”