Reproductive endocrinology and metabolism
Our group’s research activities aim to yield new key information on the pathophysiology of polycystic ovary syndrome (PCOS), the most common female endocrine and metabolic disorder.
The etiology of PCOS is not well understood, but genetic, epigenetic, and environmental factors have been implicated in its development. We also investigate the effect and mechanisms of acupuncture and/or exercise on reproductive function, hyperandrogenemia and insulin resistance as well as on key molecular pathways and epigenetic modifications in adipose and skeletal muscle tissues.
|Elisabet Stener-Victorin||Research group leader|
|Romina Fornes||PhD student|
|Milana Kokosar||PhD student|
|Eva Lindgren||Research Engineer|
|Maria Manti||PhD student|
Former group members
|Min Hu||Post doc|
|Lisa Lindheim||PhD Candidate, Medical University of Graz, Austria|
|Rodrigo Marcondes||PhD student|
Group members outside Karolinska Institutet
|Anna Benrick||MSc, PhD, Researcher, Gothenburg University, Sweden|
|Emma A Nilsson||Researcher, PhD, Lund University|
|Josefin Katakoa||Doctoral student, Gothenburg University, Sweden|
|Manuel Maliqueo||PhD, University of Chile, Santiago|
Developmental origin of androgen excess, insulin resistance and behavioral dysfunction in females
The etiology of PCOS is not well understood but emerging evidence suggests that PCOS originates, at least in part, in fetal life and elevated maternal androgens and/or maternal obesity have been implicated to play a role, however the mechanisms are largely unknown. Maternal sex steroids and metabolic hormones regulate placental steroidogenesis and the transport of nutrients, functions that are critical for fetal growth and development. Maternal androgen excess and obesity might alter metabolism, sex steroid levels and nutrition delivery to the fetus via the placenta. In this project we propose that changes in placental function are involved in the intrauterine programming of PCOS.
The overall hypothesis is that high maternal androgens and maternal obesity up-regulate placental steroid receptors and steroidogenic enzymes, which in turn alter metabolic pathways and contribute to the development of PCOS and related symptoms in the offspring.
Genome-wide DNA methylation and gene expression profiles in adipose and skeletal muscle tissue from women with and without PCOS
The possibility of an epigenetic component of PCOS has only recently been explored. Interestingly, epigenetic modification of PGC-1α has been reported in granulosa cells from women with PCOS and a genome-wide methylation array of adipose tissue from prenatally androgenized female rhesus monkeys showed changes in methylation of genes in the TGF-β superfamily. These observations suggest that epigenetic modifications could be involved in diseases such as PCOS.
This project aims to investigate differences in genome-wide gene expression and DNA methylation pattern in subcutaneous adipose tissue and skeletal muscle from women with and without PCOS. To investigate the importance of differential expression in adipose tissue, selected genes are biologically validated in a second case-control cohort matched for age, weight and BMI.
To elucidate the effect and mechanisms of acupuncture and exercise on insulin resistance and key signaling pathways in adipose and skeletal muscle tissue in translational studies
Because women with PCOS require long-term treatment and current treatments often have severe metabolic and gastrointestinal side effects, there is a need for novel treatment options. Physical exercise and acupuncture with low-frequency electrical stimulation, both induces ovulation and decreases circulating androgens. In this project, we hypothesize that acupuncture treatment with muscle contractions, by reducing hyperandrogenemia and reversing insulin resistance, can modify key molecular alterations and epigenetic changes to the genomic DNA in adipose tissue and skeletal muscle to the same extent as exercise.
Further, as the effect of acupuncture with low-frequency electrical stimulation are hypothesized to be mediated via sympathetic nervous system and/or dopaminergic system, we will administer blockers of α-adrenoceptor, β-adrenoceptor or dopamine1(D1)receptor, to elucidate which key signaling pathways mediate the effect in ovaries, adipose tissue and skeletal muscle.
- Swedish Research Council
- Novo Nordisk Foundation
- Strategick Research Program of Diabetes (SRP Diabetes)
- Karolinska Institutet
- Jane and Dan Olsson Foundation
- ALF 2015-2017
- Professor Charlotte Ling, Lund University
- Professor Inger Sundström-Pooroma, Uppsala University
- Associate Professor Carl Johan Behre, University of Gothenburg
- Professor Claes Ohlsson, University of Gothenburg
- Professor Håkan Billig, University of Gothenburg
- Professor Mats Brännström, University of Gothenburg
- Professor Angelica Lindén Hirschberg, Karolinska Institutet
- Professor, Kurt Højlund, Diabetes Research Center, Odense University, Denmark
- Professor Eszter Vankey, Norweigan University of Science and Technology, Trondheim, Norway
- Professor Matti Poutanen, Turku University, Finland
- Associate Professor, Laure Morin Papunen, University of Oulu, Finland
- Professor Thomas Jansson, University of Colorado, Denver, US
- Professor Fernand Labrie, Laval University, Canada
- Professor Andrea Dunaif, Northwestern University, Chicago, US
- Professor, Richard Legro, Pennsylvania State University, US
- Professor Xiaoke Wu, Professor, Heiljongjiang University of Traditional Chinese Medicine, Harbin, China
List of most recent publications:
Acupuncture for Infertility in Polycystic Ovary Syndrome-Reply.
JAMA 2017 10;318(15):1502
Acupuncture for Infertility in Women with Polycystic Ovary Syndrome: What Does It Add?
Semin. Reprod. Med. 2017 07;35(4):353-358
Weight Management Interventions in Women with and without PCOS: A Systematic Review.
Nutrients 2017 Sep;9(9):
Bone markers in polycystic ovary syndrome: A multicentre study.
Clin. Endocrinol. (Oxf) 2017 Dec;87(6):673-679
The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.
Sci Rep 2017 Aug;7(1):8066
Adiponectin protects against development of metabolic disturbances in a PCOS mouse model.
Proc. Natl. Acad. Sci. U.S.A. 2017 08;114(34):E7187-E7196
Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.
JAMA 2017 06;317(24):2502-2514
Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture.
FASEB J. 2017 08;31(8):3288-3297
Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.
Mol. Cell. Endocrinol. 2017 Jun;448():66-76
Should we individualize lipid profiling in women with polycystic ovary syndrome?
Hum. Reprod. 2017 Apr;32(4):966
2013 Julia Johansson, Msc Medical Engineering. PhD.
Title of thesis: Polycystic ovary syndrome - Effect of acupuncture on insulin resistance and neuroendocrine function. Institute of Neuroscience and Physiology, Endocrinology, University of Gothenburg.
2010 Elizabeth Jedel, PhD.
Title of thesis: Polycystic Ovary Syndrome: Studies of affective symptoms in association with sex steroids and evaluation of electroacupuncture and physical exercise. Institute of Clinical Neuroscience, OCIM, Karolinska Institute, Stockholm.
2010 Louise Mannerås Holm, PhD.
Title of thesis: Polycystic ovary syndrome: Studies of metabolic and ovarian disturbances and effects of physical exercise and electro-acupuncture. Institute of Neuroscience and Physiology, University of Gothenburg.
2009 Lena Svedberg, PhD.
Title of thesis: Cold feet in children with neurological disorders. Institute of Neuroscience and Physiology, University of Gothenburg.
2007 Annika Billhult, PhD.
Title of thesis: The effect of massage for women with breast cancer. Institute of Neuroscience and Physiology, University of Gothenburg.
2005 Luigi Manni, PhD.
Title of thesis: Adrenoceptors and Nerve Growth Factor: Effects of Electro-Acupuncture and Physical Exercise in Rats with Steroid-Induced Polycystic Ovaries. Cardiovascular Institute, University of Gothenburg
2000 Elisabet Stener-Victorin, PhD.
Title of thesis: Acupuncture in Reproductive Medicine - Applications in Human Assisted Reproduction and Aspects of Clinical and Experimental Neuroendocrinology. Department of Obstetrics and Gynecology, University of Gothenburg.