| 1. |
- van Duursen, MBM, et al.
(författare)
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Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals-The FREIA Project
- 2020
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.
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| 5. |
- Hallberg, Ida, et al.
(författare)
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Suspect and non-target screening of ovarian follicular fluid and serum : identification of anthropogenic chemicals and investigation of their association to fertility
- 2021
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Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 23:10, s. 1578-1588
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Tidskriftsartikel (refereegranskat)abstract
- In this work, ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry-based suspect and non-target screening was applied to follicular fluid (n = 161) and serum (n = 116) from women undergoing in vitro fertilization in order to identify substances that may be associated with decreased fertility. Detected features were prioritized for identification based on (i) hazard/exposure scores in a database of chemicals on the Swedish market and an in-house database on per- and polyfluoroalkyl substances (PFAS); (ii) enrichment in follicular fluid relative to serum; and (iii) association with treatment outcomes. Non-target screening detected 20 644 features in follicular fluid and 13 740 in serum. Two hundred and sixty-two features accumulated in follicular fluid (follicular fluid: serum ratio >20) and another 252 features were associated with embryo quality. Standards were used to confirm the identities of 21 compounds, including 11 PFAS. 6-Hydroxyindole was associated with lower embryo quality and 4-aminophenol was associated with higher embryo quality. Overall, we show the complexity of follicular fluid and the applicability of suspect and non-target screening for discovering both anthropogenic and endogenous substances, which may play a role in fertility in women.
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| 7. |
- Hao, J., et al.
(författare)
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Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix
- 2020
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Ingår i: Journal of Assisted Reproduction and Genetics. - : Springer. - 1058-0468 .- 1573-7330. ; 37, s. 2137-2150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Our purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components. Methods: Expression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS. Results: Approximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, β-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells. Conclusions: LN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.
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| 8. |
- Pampanini, V, et al.
(författare)
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Fertility Preservation for Prepubertal Patients at Risk of Infertility: Present Status and Future Perspectives
- 2021
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 93:11-12, s. 599-608
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Tidskriftsartikel (refereegranskat)abstract
- The increasing cure rate of cancer has led to a vast population of survivors having to face the late adverse effects of oncological treatments, with fertility impairment being one of the most sensitive issues for patients. Different options to preserve the fertility of adult patients are routinely used in clinical practice. However, fertility preservation strategies for prepubertal patients at risk of infertility are limited to the cryopreservation of immature gonadal tissue. In recent decades, many research efforts have been focused on the future use of cryopreserved gonadal tissue. This review discusses the common status of fertility preservation measures for pediatric patients undergoing gonadotoxic treatment, focusing especially on the challenges that remain to be solved in order to implement this fundamental service.
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