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The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedure and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility. The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments. Lack of counselling was identified as the major reason for not receiving ovarian tissue cryopreservation. A longer interval from scheduling gonadotoxic therapy to cryopreservation correlated with a higher exposure to alkylating agents of the ovarian tissue. The long-term ovarian function was mainly influenced by age at the time of gonadotoxic treatment. Current selection criteria for ovarian tissue cryopreservation should be implemented in order to stratify patients at risk of infertility and timely identify those at higher risk, especially in relation to age and pubertal stage. Efforts to increase healthcare providers' awareness and facilitate guided timing in relation to the treatment protocols are needed to guarantee early access to ovarian tissue cryopreservation for all patients at high risk of infertility.

There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-beta (ER-beta; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-beta knock-out mice (ER-beta(-/-)) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-beta(-/-) mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-beta(-/-), but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-alpha (listed as ESR1 in the MGI Database) and ER-beta in the nuclei of some neurons in the inner ear in WT mice, but no ER-beta was found in the ER-beta(-/-) mice as expected. ER-alpha staining was predominant in the nuclei of large neurons and ER-beta in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-beta is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.

Major reproductive events such as menstruation, ovulation, implantation, and cervical ripening are characterized by an increased number of invading leukocytes in the tissues. Sex steroid hormones, particularly estrogens, play an important role in these dynamic changes in the female reproductive tract. Estrogens have also been implicated in the pathogenesis of many common pathological conditions associated with leukocyte infiltration and immunological dysfunction, such as auto-immune diseases and atherosclerosis. Although the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, have been found in different leukocyte populations in tissues and in peripheral blood, there is still very little known about functional activity and importance of ERs in blood cells. To elucidate the different roles for ERalpha and ERbeta in peripheral blood leukocytes, we used microarray gene expression profiling of rat peripheral blood leukocytes subjected to in vivo treatment with estradiol (E2), the selective ERalpha agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), and the selective ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). We report the identification of genes that were commonly regulated by E2, PPT, and DPN, and genes that were regulated either by the ERalpha or ERbeta agonist. Further confirmatory analyses of the selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin B are also presented. These results were then compared with those from the uterine tissue of the same animals. Our study demonstrates that peripheral blood leukocytes are responsive to estrogens. E2 and selective ERalpha and ERbeta agonists regulate a number of genes that may contribute to inflammation and remodeling of the extracellular matrix.