| Autor: |
Pallotti F; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Senofonte G; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Konstantinidou F; Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy.; Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy., Di Chiano S; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Faja F; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Rizzo F; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Cargnelutti F; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Krausz C; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, 50139 Florence, Italy., Paoli D; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Lenzi A; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy., Stuppia L; Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy.; Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy., Gatta V; Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy.; Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, 66100 Chieti, Italy., Lombardo F; Laboratory of Seminology-Sperm Bank 'Loredana Gandini', Department of Experimental Medicine, University of Rome 'Sapienza', 00161 Rome, Italy. |
| Abstrakt: |
Virilization of gender-incongruent subjects to whom were assigned the female gender at birth (AFAB) is achieved through testosterone administration. Inter-individual differences in the timing and acquisition of phenotypic characteristics, even if the same hormone preparations and regimens are used, are frequently observed. Polymorphisms of sex hormone receptors and methylation of their gene promoters, as well of several imprinted genes as H19, may underlie the differential response to treatment. Thus, the aim of this study was to examine the possible relationship between the CpG methylation profile of the estrogen receptor 2 gene ( ESR2 ) and H19 promoters and their influence on phenotype modifications in a cohort of AFAB people at baseline (T0) and after 6 mo (T6) and 12 mo (T12) of testosterone therapy (testosterone enanthate, 250 mg i.m. every 28 d). A total of 13 AFAB subjects (mean age 29.3 ± 12.6) were recruited. The percentage of methylation of the ESR2 promoter significantly increased at T6 (adj. p = 0.001) and T12 (adj. p = 0.05), while no difference was detected for H19 ( p = 0.237). Methylation levels were not associated with androgen receptor (AR)/estrogen receptor beta (ERβ) polymorphisms nor hormone levels at baseline and after six months of treatment. On the other hand, total testosterone level and patient age resulted in being significantly associated with ESR2 methylation after twelve months of treatment. Finally, the difference in ESR2 promoter methylation between T6 and baseline was significantly associated with the number of CA repeats of the ERβ receptor, adjusted vs. all considered variables (R 2 = 0.62, adj. R 2 = 0.35). No associations were found with CAG repeats of the AR , age, and estradiol and testosterone levels. Despite the small sample size, we can hypothesize that treatment with exogenous testosterone can modify the ESR2 methylation pattern. Our data also indicated that epigenetic changes may be regulated, suggesting that the modulation of estrogen signaling is relevant shortly after the beginning of the treatment up to T6, with no further significant modification at T12. Furthermore, estrogen receptor methylation appears to be associated with the age of the subjects and exogenous testosterone administration, representing a marker of androgenic treatment. Nonetheless, it will be necessary to increase the number of subjects to evaluate how epigenetic regulation might play a relevant role in the modulation of phenotypical changes after testosterone treatment. |
