Biomaterial Database

Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring. 2015

Min Hu, and Jennifer Elise Richard, and Manuel Maliqueo, and Milana Kokosar, and Romina Fornes, and Anna Benrick, and Thomas Jansson, and Claes Ohlsson, and Xiaoke Wu, and Karolina Patrycja Skibicka, and Elisabet Stener-Victorin

Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China;

During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011297	Prenatal Exposure Delayed Effects	The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH.	Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D011944	Receptors, Androgen	Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.	Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D005260	Female		Females
D000679	Amygdala	Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.	Amygdaloid Body,Amygdaloid Nuclear Complex,Amygdaloid Nucleus,Archistriatum,Corpus Amygdaloideum,Intercalated Amygdaloid Nuclei,Massa Intercalata,Nucleus Amygdalae,Amygdalae, Nucleus,Amygdaloid Bodies,Amygdaloid Nuclear Complices,Amygdaloid Nuclei, Intercalated,Amygdaloid Nucleus, Intercalated,Amygdaloideum, Corpus,Amygdaloideums, Corpus,Archistriatums,Complex, Amygdaloid Nuclear,Complices, Amygdaloid Nuclear,Corpus Amygdaloideums,Intercalata, Massa,Intercalatas, Massa,Intercalated Amygdaloid Nucleus,Massa Intercalatas,Nuclear Complex, Amygdaloid,Nuclear Complices, Amygdaloid,Nuclei, Intercalated Amygdaloid,Nucleus, Amygdaloid,Nucleus, Intercalated Amygdaloid
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001007	Anxiety	Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.	Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors
D013739	Testosterone	A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.	17-beta-Hydroxy-4-Androsten-3-one,17-beta-Hydroxy-8 alpha-4-Androsten-3-one,8-Isotestosterone,AndroGel,Androderm,Andropatch,Androtop,Histerone,Sterotate,Sustanon,Testim,Testoderm,Testolin,Testopel,Testosterone Sulfate,17 beta Hydroxy 4 Androsten 3 one,17 beta Hydroxy 8 alpha 4 Androsten 3 one,8 Isotestosterone