In the ovaries, there are ovarian follicles that contain immature egg cells. Throughout a woman's lifetime, a portion of these will grow and mature for ovulation, which enables pregnancy and reproductive health. If chemicals affect immature eggs, the consequence can be reduced fertility.
Our research is divided into various subject areas:
- We use population studies to determine the relationship between environmental exposures and fertility in women,
- We study how certain medical treatments, such as chemotherapy, affect the ovaries of girls and young women,
- We analyze the cellular composition and function of the ovaries throughout a woman’s life, from birth to menopause,
- We test how chemicals affect the ovaries through exposure studies on tissue and cell cultures, and
- We develop in vitro models that mimic ovaries to test the toxicity of chemicals and pharmaceuticals.
Environmental Exposures and Women's Fertility
Our goal is to identify links between chemicals and fertility in women. We have measured concentrations of approximately 50 different environmental chemicals in serum samples collected from pregnant women and women undergoing fertility treatment. Our statistical analyses have shown that higher levels of several chemicals are related to a longer "time-to-pregnancy," i.e., the time it takes to become pregnant from when one starts trying. Furthermore, we have identified relationships between exposure and the number of immature eggs remaining in the ovaries, as well as a number of other markers of ovarian health.
Selected publications
”Ambient black carbon particles in human ovarian tissue and follicular fluid.” Bongaerts E, et al. 2023 Environ Int.
”Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment.” Hallberg I, et al. 2023 J Expo Sci Environ Epidemiol.
”Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia.” Bellavia A, et al. 2023 Environ Res.
“Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies” Björvang et al. 2021 Environ Res
“Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women” Björvang et al. 2021 Environ Int
“Persistent organic pollutants, pre-pregnancy used of combined oral contraceptives, age and time-to-pregnancy in the SELMA cohort” Björvang et al. accepted for publication in Environ Health
Impact of Medical Treatments on the Ovary
Some medical treatments, such as chemotherapy, can save lives but at the same time damage the ovaries and fertility. To enable future opportunities to have children, egg cells or ovarian tissue can be frozen before treatment begins. For children who have not yet gone through puberty, freezing ovarian tissue is the only option. The method is well-proven for adult women but less studied in children. We have initiated a national study, Sveafertil, where girls and young women at very high risk of infertility as a result of their treatments can freeze a part of their ovary and donate a small part for our research. Our goal is to compare ovarian tissue from children with adult tissue in detail and to identify molecules and cells affected by chemotherapy, and with this knowledge, refine methods for the youngest patients.
Selected publications
”Reference standards for follicular density in ovarian cortex from birth to sexual maturity.” Hassan J, et al. 2023 Reprod Biomed Online
”Fertility Preservation for Prepubertal Patients at Risk of Infertility: Present Status and Future Perspectives.” Pampanini V, et al. 2020 Horm Res Paediatr.
”Impact of first-line cancer treatment on the follicle quality in cryopreserved ovarian samples from girls and young women.” Pampanini V, et al. 2019 Hum Reprod.
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Detailed Cellular Map of the Ovary Throughout Life
To study how environmental exposures and medical treatments affect the ovary, we must understand its function at a cellular and molecular level. One of our research goals is therefore to identify different cell types within the ovary and study how these change throughout life. The ovary undergoes changes, for example, during puberty, but the impact on the smallest follicles, which contain immature eggs, is not well studied. We analyze ovarian samples from girls, young women, and adult women to create a comprehensive picture of the ovary's development and function from childhood, through puberty, to adulthood. This detailed information will give us better conditions to map the environmental impact on the ovary, develop better test methods for reproductive toxicity, and understand the factors that contribute to infertility.
Selected publications
”Transcriptomics and Spatial Proteomics for Discovery and Validation of Missing Proteins in the Human Ovary.” Méar L, et al. 2024 J Proteome Res.
”Spatial Proteomics for Further Exploration of Missing Proteins: A Case Study of the Ovary” Mear et al. 2022 J Proteome Res
”Single-cell Analysis of Human Ovarian Cortex Identifies Distinct Cell Populations but No Oogonial Stem Cells” Wagner et al. 2020 Nat Commun
ONLINE RESURS E-ovary
Impact of Environmental Exposures on the Ovary
To determine if environmental exposures directly affect the ovary, we conduct controlled exposure experiments in the laboratory. We expose ovarian tissue and cultured cells to chemicals that we have identified in our population studies on chemicals and female fertility. We investigate whether the exposed follicles grow normally and which genes are affected. Our results show how and through which molecular mechanisms ovarian function can be affected by environmental factors. This information can be used to better understand the relationship between exposure and reduced fertility in women, as well as to develop tests to evaluate the reproductive toxicity of chemicals.
Selected publications
”Identification of phthalate mixture exposure targets in the human and mouse ovary in vitro.” Tarvainen I, et al. 2023 Reprod Toxicol.
”Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models.” Li T, et al. 2023 Toxicology.
“AOP key event relationship report: Linking decreased androgen receptor activation with decreased granulosa cell proliferation of gonadotropin-independent follicles” Panagiotou et al. 2022 Reprod Tox
”Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals.” Johansson et al. 2020 Arch Toxicol
Development of In Vitro Models that Mimic Ovaries
We use ovarian tissue to develop in vitro models that mimic the ovary or can replicate its various functions. Such models are necessary to assess the toxicity of chemicals in the laboratory in a human-relevant way, without the use of experimental animals. Furthermore, models that mimic ovaries could in the future be used to mature egg cells in vitro.
Selected publications
“Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix” Hao et al. 2020 J Assist Reprod Genet
Additional information
Our studies on ovarian function are inspired by Professor Emerita Outi Hovatta and her long career as well as groundbreaking research in ovarian biology.
The studies we conduct on human ovarian tissue are made possible thanks to patients undergoing various surgeries at Karolinska University Hospital who choose to participate in our research. Without these participants and our clinical collaborators, the research would be impossible to conduct. We would like to express our warm thanks to all the patients, midwives, and doctors who make our research possible!
All our studies are approved by the Ethical Review Authority, and tissue is only collected from patients who have been informed about our studies and have given their consent.
We are proud to be part of several extensive collaborations across Europe that are funded by the EU. Here you can read about MERLON (2024-2028), FREIA (2019-2024), and ERIN (2020-2023).
MERLON
Website: under construction
Description: "Enhanced identification of endocrine disruptors through integration of science-based regulatory practices and innovative methodologies: The MERLON Project" - Svingen et al., 2024, Open Research Europe
FREIA
"Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals - The FREIA Project" - van Duursen et al., 2020, International Journal of Molecular Sciences
ERIN
Research presentations online
Keynote Lecture on Chemicals and Fertility in Women at Helsinki One Health Symposium (2020)
Presentation on EDCs, Plastics and Human Health at UNDP global webinar series and Endocrine Society press release event (2021)