establishment-rat-models-mimicking-gender-affirming-hormone

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

Transgender (TG) people are individuals whose gender identity and sex assigned at birth do not match. They often undergo gender-affirming hormone therapy ...

Istituto Superiore di Sanità

Transgender (TG) describes individuals whose gender identity differs from the social norms. TG people undergoing gender-affirming hormone therapy (HT) may be considered a sub-group of the population susceptible to environmental contaminants for their targets and modes of action. The aim of this study is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex were subcutaneously exposed to three doses of HT (plus control) selected starting from available data. The demasculinizing-feminizing models (dMF) were β-estradiol plus cyproterone acetate, at 0.09 + 0.33, 0.09 + 0.93 and 0.18 + 0.33 mg, respectively, five times/week. The defeminizing-masculinizing models (dFM) were testosterone (T) at 0.45, 0.95 and 2.05 mg, two times/week. Clitoral gain and sperm count, histopathological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 were evaluated. In the dMF model, the selected doses-leading to T serum levels at the range of the corresponding cisgender-induced strong general toxicity and cannot be used in long-term studies. In the dFM model, 0.45 mg of T represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suitable biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models.

Risk Assessment of Transgender People: Development of Rodent Models Mimicking Gender-Affirming Hormone Therapies and Identification of Sex-Dimorphic Liver Genes as Novel Biomarkers of Sex Transition.

Individuals whose gender identity differs from the biological sex and the social norms are defined as transgender. Sometimes transgender undergo gender affirming hormone therapy, which lasts for the entire life making essential to evaluate its potential long-term effects. Moreover, transgender can represent a susceptible sub-group of population and specific attention is needed in risk assessment, including the development of targeted animal models. Aim of the study is the implementation of a rodent demasculinizing-feminizing model through the setting of appropriate dose of hormone therapy and the selection of specific biomarkers to evaluate the sex transition. Specific attention is paid to thyroid homeostasis due to the close link with reproductive functions. Four male adult rats/group were subcutaneously exposed to three doses plus control of β-estradiol valerate plus cyproterone acetate at: 0.045 + 0.2 (low), 0.09 + 0.2 (medium) and 0.18 + 0.2 (high) mg/dose, five times/week. The doses were selected considering the most recent recommendations for transgender woman. Sperm count, histopathological analysis (testis, liver, thyroid), testosterone, estradiol, triiodothyronine and thyroid-stimulating hormone serum levels and gene expression of sex dimorphic CYP450 were evaluated.

Risk assessment of transgender people: implementation of a demasculinizing-feminizing rodent model including the evaluation of thyroid homeostasis.

Correction: Risk assessment of transgender people: implementation of a demasculinizing-feminizing rodent model including the evaluation of thyroid homeostasis.

Article	Year
Risk Assessment of Transgender People: Development of Rodent Models Mimicking Gender-Affirming Hormone Therapies and Identification of Sex-Dimorphic Liver Genes as Novel Biomarkers of Sex Tr... Cells\| PubMed ID: 36766819	2023
Risk assessment of transgender people: implementation of a demasculinizing-feminizing rodent model including the evaluation of thyroid homeostasis. Biology direct\| PubMed ID: 38166984	2024
Correction: Risk assessment of transgender people: implementation of a demasculinizing-feminizing rodent model including the evaluation of thyroid homeostasis. Biology direct\| PubMed ID: 38291501	2024

Luigia Cancemi

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