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The ovary contains the female germ cells known as oocytes, which are essential for female fertility. The immature oocytes reside within primordial follicles in the ovarian cortex and are referred to as the ovarian reserve. Disruption of ovaries by various external factors, such as environmental pollutants, medical conditions, and gonadotoxic treatments can impair fertility. While the pathways behind disruption have been studied in adult ovarian tissue, much remains to be elucidated, especially regarding paediatric ovarian tissue. The molecular and transcriptomic landscape of ovarian tissue from children remains poorly characterised, making it even more challenging to estimate its sensitivity to ovarian disruption. Ovarian tissue cryopreservation is an established method for preserving fertility in adults requiring gonadotoxic treatments, resulting in nearly 300 live births. Paediatric ovarian tissue is cryopreserved using the protocols as in adults, despite previous studies showing differences in the competency of residing follicles. Additionally, patients requiring fertility preservation often have received gonadotoxic treatments or have medical conditions associated with infertility prior to fertility preservation, urging further study of their effect on the ovarian reserve. This thesis aims to provide a better understanding of i) the basic biology of the ovary from birth to reproductive age, and ii) the effect of chemical exposures and medical intervention on the ovary through histologic and transcriptomic assessment of the ovarian cortex in patients from child- to adulthood. Paper I and paper II histologically quantified cortical follicles in biopsied ovarian tissue to elucidate the associations between different exposures and the ovarian reserve. In paper I the association between serum levels of 31 environmental pollutants and both the ovarian reserve and odds of infertility were investigated in a cohort of pregnant women. Some pollutants correlated negatively

Multiple studies have shown associations between exposure to endocrine disrupting chemicals (EDCs) and reduced fertility in women. However, little is known about the target organs of chemical disruption of female fertility. Here, we focus on the hormone-sensitive uterine lining, the endometrium, as a potential target. Decidualization is the morphological and functional change that endometrial stromal cells undergo to support endometrial receptivity, which is crucial for successful implantation, placentation, and pregnancy. We investigated the effect of nine selected EDCs on primary human endometrial stromal cell decidualization in vitro. The cells were exposed to a decidualization-inducing mixture in the presence or absence of 1 mu M of nine different EDCs for nine days. Extent of decidualization was assessed by measuring the activity of cAMP dependent protein kinase, Rho-associated coiled-coil containing protein kinase, and protein kinase B in lysates using photoluminescent probes, and secretion of prolactin into the media by using ELISA. Decidualization-inducing mixture upregulated activity of protein kinases and prolactin secretion in cells derived from all women. Of the tested chemicals, dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and perfluorooctanesulfonic acid (PFOS) significantly reduced decidualization as judged by the kinase markers and prolactin secretion. In addition, bisphenol A (BPA) reduced prolactin secretion but did not significantly affect activity of the kinases. None of the EDCs was cytotoxic, based on the assessment of total protein content or activity of the viability marker casein kinase 2 in lysates. These results indicate that EDCs commonly present in the blood circulation of reproductive-aged women can reduce decidualization of human endometrial stromal cells in vitro. Future studies should focus on detailed hazard assessment to define possible risks of EDC exposure to endometrial dysfunction and implantation failur