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10.3390/cells12030474
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Article

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

by
Roberta Tassinari
1,*,
Alessia Tammaro
1,
Gabriele Lori
1,
Sabrina Tait
1,
Andrea Martinelli
2,
Luigia Cancemi
2,
Paolo Frassanito
2 and
Francesca Maranghi
1,*
1
Center for Gender Specific Medicine, Istituto Superiore di Sanità, 00144 Rome, Italy
2
Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00144 Rome, Italy
*
Authors to whom correspondence should be addressed.
Cells 2023, 12(3), 474; https://doi.org/10.3390/cells12030474
Submission received: 15 November 2022 / Revised: 19 January 2023 / Accepted: 25 January 2023 / Published: 1 February 2023
(This article belongs to the Topic Animal Models of Human Disease)
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Abstract

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.
Keywords: testosterone; estrogen; cyproterone acetate; masculinizing; feminizing; cytochrome P450; sex-specific genes testosterone; estrogen; cyproterone acetate; masculinizing; feminizing; cytochrome P450; sex-specific genes

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MDPI and ACS Style

Tassinari, R.; Tammaro, A.; Lori, G.; Tait, S.; Martinelli, A.; Cancemi, L.; Frassanito, P.; Maranghi, F. 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. Cells 2023, 12, 474. https://doi.org/10.3390/cells12030474

AMA Style

Tassinari R, Tammaro A, Lori G, Tait S, Martinelli A, Cancemi L, Frassanito P, Maranghi F. 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. Cells. 2023; 12(3):474. https://doi.org/10.3390/cells12030474

Chicago/Turabian Style

Tassinari, Roberta, Alessia Tammaro, Gabriele Lori, Sabrina Tait, Andrea Martinelli, Luigia Cancemi, Paolo Frassanito, and Francesca Maranghi. 2023. "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" Cells 12, no. 3: 474. https://doi.org/10.3390/cells12030474

APA Style

Tassinari, R., Tammaro, A., Lori, G., Tait, S., Martinelli, A., Cancemi, L., Frassanito, P., & Maranghi, F. (2023). 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. Cells, 12(3), 474. https://doi.org/10.3390/cells12030474

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