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Endocrine Abstracts (2021) 73 AEP451 | DOI: 10.1530/endoabs.73.AEP451

1University of A Coruña, Center for Advanced Scientific Research (CICA), Department of Psychology, A Coruna, Spain; 2Ghent University, Department of Endocrinology and Department of Experimental Clinical and Health Psychology, Ghent, Belgium; 3Venezuelan Institute for Scientific Research (IVIC), Center for Biophysics and Biochemistry. Laboratory of Neurophysiology, Caracas, Bolivarian Republic of Venezuela; 4UNED, Department of Psychobiology, Madrid, Spain.


In mammals, the gonads and the brain develop from bipotential organs that will differentiate into female or male organs, during a critical period of development. This process begins with the production of testosterone by the testes, which will be converted into estradiol in the brain, by the aromatase. While the end is defined by the moment when the inhibition of androgens (in males), or treatment with estrogens (in females), stops having an effect on brain dimorphism. But in humans, biological sex and brain sex are not always coincident. Thus, transgender females are born with male genitalia. Their sex is male, but their gender is female. In contrast, transgender males are born with female genitalia. Their sex is female but their gender is male. These people generally show gender incongruence (GI), due to the incongruence between sex and gender.

The origin of GI is complex, where neurological, hormonal and genetic factors play an important role. One of the current hypotheses suggests that GI could be related to a different sexual differentiation of the brain, not concordant with gender. But other processes are also involved. Thus epigenetics, specifically DNA methylation, can alter the chromatin structure, modifying the access of transcription factors to the promoter regions, modulating gene expression. Thus, 16 trans people were compared with 16 cis people, with the same geographic origin, ethnicity and sex. Methylation analysis was performed on blood, using the Infinium Human Methylation 850K BeadChip. The changes in methyloma were analyzed with the Partek Genomics Suite program. When we compared methylome of cis and trans populations with the same sex assigned at birth, we found significant differences in 71, 515 CpGs that passed the criterion FDR p <0.05 (28.5% located in islands). When we compared cis men vs. trans women we found 20 CpG islands that passed both criteria (FDR p<0.05; fold change ≥ ± 2). The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, UBALD1 and PLEKHA5. With respect to populations assigned female at birth, when we compared cis women vs. trans men, we found 4 CpGs that passed both criteria. The results of enrichment tests yielded significant over-representation for the categories of biological process, cellular component and molecular function ontologies: negative regulation of gene expression, positive regulation of catalytic activity, ribonucleotide binding, RNA binding, among others.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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