Center for Gender Specific Medicine, Istituto Superiore di Sanità, 00144 Rome, Italy.
Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00144 Rome, Italy.
Cells. 2023 Feb 1;12(3):474. doi: 10.3390/cells12030474.
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.
跨性别者（TG）描述的是其性别认同与社会规范不同的个体。正在接受性别肯定激素治疗（HT）的 TG 人可能因其作用目标和作用方式而被视为易受环境污染物影响的人群的一个亚组。本研究的目的是设定适当的 HT 剂量并确定特定的生物标志物，以实施 TG 动物模型。每组/性别有四只成年大鼠，经皮下暴露于从现有数据中选择的三种 HT 剂量（加对照）。去势-女性化模型（dMF）为雌二醇加醋酸环丙孕酮，剂量分别为 0.09 + 0.33、0.09 + 0.93 和 0.18 + 0.33 mg，每周 5 次。去女性化-男性化模型（dFM）为睾酮（T），剂量分别为 0.45、0.95 和 2.05 mg，每周 2 次。评估阴蒂增大和精子计数、生殖器官和肝脏的组织病理学分析、激素血清水平和性别二态 CYP450 的基因表达。在 dMF 模型中，所选剂量导致 T 血清水平处于相应顺性别诱导的强全身毒性范围内，不能用于长期研究。在 dFM 模型中，0.45mg 的 T 代表正确剂量。此外，所选终点被认为是合适和可靠的，可以实施动物模型。性别特异性 CYP 表达是设定适当（去）去势-（去）女性化 HT 和实施 TG 动物模型的合适生物标志物。
