Chemicals and female fertility
Pauliina Damdimopoulou, PhD, Docent in endocrine physiology
Our team studies whether exposure to chemicals can affect fertility in women. In particular, we are interested in chemicals that have hormone disruptive activity (endocrine disruptive chemical, EDC), because the reproductive health of a woman is dependent on timely and appropriate action of hormones. For example, the maturation of oocytes within follicles in the ovaries is controlled by pituitary hormones as well as local ovarian growth factors. The maturing follicle in turn produces sex hormones that prepare the uterus for possible pregnancy. Disruption of these signaling events by chemicals could lead to difficulties becoming pregnant.
Fertility problems in humans are common. Approximately 10-15 % of all couples suffer from involuntarily infertility. In Sweden, 19 000 IVF treatments are carried out each year resulting in over 4 000 babies (3,8 % of all births). Although many couples can become parents with the help of IVF, about one third remain childless.
It is important to study whether chemical exposures could be one reason for infertility, since exposure can be modified through lifestyle choices. In addition, better understanding of effects of chemicals on fertility could ultimately lead to changes in chemical legislation, reducing the usage of harmful chemicals.
We carry out our work at Swetox Södertälje in Gärtuna, and at Campus Flemingsberg.
Damdimopoulou Lab retreat on Viking Grace in January, 2017. From the left: Captain, Pauliina, Astrud, Marie-Therese, Leni, Ida, Valentina, Richelle and Sara
PI Pauliina Damdimopoulou, PhD, Docent (Pauliina.firstname.lastname@example.org)
Postdoc Astrud Tuck, PhD (email@example.com)
PhD student Magdalena “Leni” Wagner, MSc (Magdalena.firstname.lastname@example.org)
PhD student Richelle Duque Björvang, MD, MSc (email@example.com)
Trainee Ashwini Gajulapuri, MSc
MSc student Elinor Hansson
MSc student Pernilla Bisting
Project 1: Environmental chemicals and fertility in women living in Sweden
The aim of this project is to identify chemicals and their mixtures that associate to reduced fertility in women living in Sweden. We use data from the Swedish pregnancy cohort SELMA to analyze connections between maternal exposure to chemicals and time-to-pregnancy. This is a collaboration with Prof Carl-Gustaf Bornehag from Karlstad University. We also analyze whether concentrations of chemicals in women attending IVF treatments associate to their treatment outcome. This is a collaboration with the Carl von Linnékliniken in Uppsala, and researchers Ylva Sjunnesson and Sara Persson from the Swedish University of Agricultural sciences. The work will be carried out by PhD students Richelle Duque Björvang (KI) and Ida Hallberg (SLU).
Project 2: Effects of chemical exposure in the ovary
One of our main aims is to develop human and bovine follicle culture models that are suited for the study of environmental chemicals. Our goal is to study follicle activation, maturation and death in vitro with the help of cutting edge technologies, such as real time imaging and transcriptomics. We are also characterizing different somatic cell populations in the ovary and studying their possible roles in follicle biology. These in vitro models are developed by postdoc Astrud Tuck and PhD students Leni Wagner and Jie Hao, and will be applied to chemicals and their mixtures identified in Project 1. Key collaborators are Outi Hovatta, Juha Kere and Claus Yding Andersen.
Some chemical exposures, such as cancer treatments, cause irreversible damage in the ovary. We aim to understand the events leading to follicle loss in girls and women receiving chemotherapy using patient samples. The results could help to develop protective treatments and understand general mechanisms underlying follicle loss in response to chemicals. This project is a collaboration with Kirsi Jahnukainen, Lena Sahlin and Outi Hovatta, and the work is carried out by PhD students Leni Wagner and Valetina Pampanini
Ultimately we want to discover molecular initiating events and delineate adverse outcome pathways behind chemically induced adverse effects in the ovaries. This information could be tailored for example into reporter gene models that could be used in the screening of reproductive toxicity of chemicals.
Project 3: Advanced machine learning for predicting human fetal exposure to chemicals
In this project we will map human fetal exposure to circa 20 different environmental chemicals. Our aim is to establish an in silico tool that will be able to predict fetal exposure to chemicals based on mother’s blood levels. We will use advanced machine learning (artificial intelligence) methods in collaboration with the Swetox in silico team to accomplish this goal. The key collaborators are Prof Papadogiannakis and Marie-Therese Vinnars from Karolinska University hospital, and Daniel Mucs from Swetox.
- Swedish Research Council FORMAS EDC2020 project grant (2014-2018)
- EU Horizon2020 EDC-MixRisk (2015-2018)
- Swedish Research Council FORMAS Future research leader grant (2016-2018)
- Jane & Aatos Erkko foundation grant (2016-2020)
- Karolinska Institute foundations and funds (2017)
- Swedish Research Council project grant (PI Hovatta 2015-2018)
Daniel Mucs, Johan Lindberg, Marcus Sjödin (Swetox), Outi Hovatta, Fredrik Lanner (CLINTEC), Juha Kere (BioNut), Kirsi Jahnukainen, Lena Sahlin, Valentina Pampanini (KBH), Marie-Therese Vinnars, Nikos Papadogiannakis (CLINTEC), Marie Vahter, Karin Broberg (IMM)
Karolinska University Hospital
Kerstin Palm, Karin Pettersson, Anna Sand, Boel Niklasson, Catarina Arnelo, Ulla Innalla
Swedish University of Agricultural Sciences
Ylva Sjunnesson, Sara Persson, and Ida Hallberg
Hannu Kiviranta, National institute for health and welfare, Kuopio, Finland
Claus Yding Andersen, Rigshospitalet, Copenhagen, Denmark
Yanping Li, Central South University, Changsha, Hunan, China
The Hydroxysteroid (17β) Dehydrogenase Family Gene HSD17B12 Is Involved in the Prostaglandin Synthesis Pathway, the Ovarian Function, and Regulation of Fertility.
Kemiläinen H, Adam M, Mäki-Jouppila J, Damdimopoulou P, Damdimopoulos AE, Kere J, Hovatta O, Laajala TD, Aittokallio T, Adamski J, Ryberg H, Ohlsson C, Strauss L, Poutanen M.
Endocrinology. 2016 Oct;157(10):3719-3730.
Expression and localisation of c-kit and KITL in the adult human ovary.
Tuck AR, Robker RL, Norman RJ, Tilley WD, Hickey TE.
J Ovarian Res. 2015 May 26;8:31.
Mouse GDF9 decreases KITL gene expression in human granulosa cells.
Tuck AR, Mottershead DG, Fernandes HA, Norman RJ, Tilley WD, Robker RL, Hickey TE.
Endocrine. 2015 Mar;48(2):686-95.
Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells.
Zhang H, Panula S, Petropoulos S, Edsgärd D, Busayavalasa K, Liu L, Li X, Risal S, Shen Y, Shao J, Liu M, Li S, Zhang D, Zhang X, Gerner RR, Sheikhi M, Damdimopoulou P, Sandberg R, Douagi I, Gustafsson JÅ, Liu L, Lanner F, Hovatta O, Liu K.
Nat Med. 2015 Oct;21(10):1116-8.
From pure compounds to complex exposure: Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo.
Ali I, Hurmerinta T, Nurmi T, Berglund M, Rüegg J, Poutanen M, Halldin K, Mäkelä S, Damdimopoulou P.
Toxicol Lett. 2016 Jun 24;253:27-35.
Rapid fluorescent detection of (anti)androgens with spiggin-gfp medaka.
Sébillot A, Damdimopoulou P, Ogino Y, Spirhanzlova P, Miyagawa S, Du Pasquier D, Mouatassim N, Iguchi T, Lemkine GF, Demeneix BA, Tindall AJ.
Environ Sci Technol. 2014 Sep 16;48(18):10919-28
Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment.
Rodin S, Antonsson L, Niaudet C, Simonson OE, Salmela E, Hansson EM, Domogatskaya A, Xiao Z, Damdimopoulou P, Sheikhi M, Inzunza J, Nilsson AS, Baker D, Kuiper R, Sun Y, Blennow E, Nordenskjöld M, Grinnemo KH, Kere J, Betsholtz C, Hovatta O, Tryggvason K.
Nat Commun. 2014;5:3195
We are welcoming applications from students interested in our research topics! Please email Pauliina Damdimopoulou (firstname.lastname@example.org) and cc Astrud Tuck (email@example.com) if you would like to work with us.