Pauliina Damdimopoulou

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 disrupting activities (endocrine disrupting chemical, EDC) since the reproductive health of a woman is dependent on timely and appropriate action of hormones. For example, the growth and maturation of ovarian follicles that contain the oocytes are 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 signalling events by chemicals could lead to difficulties in becoming pregnant.

Infertility is a common problem. Approximately 10-15 % of all couples suffer from involuntarily infertility. In Sweden, approximately 19 000 fertility 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 in vitro fertilization (IVF), about one third remain childless.

It is important to study whether chemical exposures could be a contributing factor for infertility since exposure can be modified through lifestyle choices. In addition, better understanding of effects of chemicals on fertility could help in designing better assays for chemical testing, which in the long run can lead to changes in chemical legislation and restrictions in the use of chemicals.
We carry out our work at Swetox Södertälje in Gärtuna and at Campus Flemingsberg of Karolinska Institutet.

Research group members

PI Pauliina Damdimopoulou, PhD, Docent (Pauliina.damdimopoulou@ki.se)
Postdoc Astrud Tuck, PhD (astrud.tuck@swetox.se)
PhD student Magdalena “Leni” Wagner, MSc (Magdalena.wagner@ki.se)
PhD student Richelle Duque Björvang, MD, MSc (richelle.duque.bjorvang@ki.se)
Trainee Ashwini Gajulapuri, MSc (ashwini.gajulapuri@swetox.se)
MSc student Elinor Hansson
MSc student Pernilla Bisting

Projects

Environmental chemicals and fertility in women living in Sweden

Aim: To identify chemicals and their mixtures that associate to reduced fertility in women living in Sweden.
Methods: We are using data from the Swedish pregnancy cohort SELMA to analyze associations between maternal exposure to chemicals and time-to-pregnancy. We are also analyzing whether chemicals in IVF patients affect the treatment outcome, baby take-home rate.

These studies are based on a collaboration with the SELMA cohort coordinator Prof Bornehag in Karlstad University, Carl von Linnékliniken in Uppsala, and Assc Prof Ylva Sjunnesson and Dr Sara Persson from the Swedish University of Agricultural Sciences (Uppsala). Chemical analyses are carried out in collaboration with Prof Kivimäki (National Institute for Health and Welfare, Finland) and Assc Prof Lindh (University of Lund).

Effects of chemical exposures in the ovary

Aim: To evaluate the effects of chemical exposure on growth, viability and function of human ovarian follicles.
Methods: We are carrying out molecular characterization of human ovarian tissue, including follicles on a single cell level to map different cell populations and signalling networks within the normal ovary. Through ovarian follicle culture experiments, we study how culture conditions and chemical exposures affect ovarian cells. In addition, we study ovarian tissue from patients who have received gonadotoxic treatments to understand the mechanisms of severe follicle damage in the ovary. These experiments will collectively tell us how different chemical insults affect ovarian cells and follicles and eventually, this information will assist in designing better assays for the prediction of ovarian toxicity of chemicals.

These projects are based on a collaboration with Swetox Bioanalysis unit, Prof Jahnukainen (University of Helsinki, Finland), Prof Kere (Karolinska Institutet) and Prof Yding Andersen (Rigshospitalet, Copenhagen), as well as Prof Emerita Hovatta.

Our studies on human ovarian tissue would not be possible without the precious tissue donations by patients attending Karolinska University Hospital, and the dedicated hospital personnel. We want to thank all the tissue donors, midwives, and doctors that make our studies possible. All our studies are covered by ethical approvals from the Stockholm Region Ethical Review Board.

Human fetal exposure to chemicals

Aim: To study human fetal exposure to environmental chemicals
Methods: This study is based on analysis of environmental chemicals in human fetal tissues and maternal serum samples obtained through maternity care and pathology department biobanks. The key collaborators are Prof Papadogiannakis and Dr Vinnars from Karolinska University hospital, and the Swetox in silico unit. Chemical analyses are carried out in collaboration with Prof Kivimäki (National Institute for Health and Welfare, Finland) and Assc Prof Lindh (University of Lund). The study has a valid ethical license from the Stockholm Region Ethical Review Board.

Research funding

  • Swedish Research Council FORMAS EDC2020 (2014-2019)
  • EU Horizon2020 EDC-MixRisk (2015-2018)
  • Swedish Research Council FORMAS Future research leader (2016-2018)
  • Jane & Aatos Erkko foundation (2016-2020)
  • Karolinska Institute foundations and funds (2017)
  • Swedish Research Council (2018-2019)
  • Childhood Cancer Foundation (2018-2020)

 

Publications

Resveratrol supports and alpha-naphthoflavone disrupts growth of human ovarian follicles in an in vitro tissue culture model.
Hao J, Tuck AR, Sjödin MOD, Lindberg J, Sand A, Niklasson B, Argyraki M, Hovatta O, Damdimopoulou P.
Toxicol Appl Pharmacol. 2018 Jan 1;338:73-82.

PLAG1 deficiency impairs spermatogenesis and sperm motility in mice.
Juma AR, Grommen SVH, O’Bryan MK, O’Connor AE, Merriner DJ, Hall NE, Doyle SR, Damdimopoulou PE, Barriga D, Hart AH, Van de Ven WJM, De Groef B.
Sci Rep. 2017 Jul 13;7(1):5317.

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.

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

 

Vacant positions

We are welcoming applications from students interested in our research topics! Please email Pauliina Damdimopoulou (pauliina.damdimopoulou@ki.se) and cc Astrud Tuck (astrud.tuck@swetox.se) if you would like to work with us.

Our research in news

Interview in Helsingin Sanomat (in Finnish)
Interview in Ny Teknik (in Swedish)