SFEBES2023 Oral Poster Presentations Reproductive Endocrinology (4 abstracts)
Exploring the sexual dimorphic development of human external genitalia
Laetitia L. Lecante 1 , Ellen Smith 2 , Peter J. O’Shaughnessy 3 , Michelle Bellingham 3 , Ugo Soffientini 3 , Zeynab Heidari 2 , Graham Hamilton 4 , Terje Svingen 5 , Rod T. Mitchell 6 & Paul A. Fowler 1
1Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeeen, United Kingdom. 2Centre for Genome-Enabled Biology and Medicine, University of Aberdeen, Foresterhill, Aberdeeen, United Kingdom. 3School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow, Bearsden Rd, Glasgow, United Kingdom. 4Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. 5National Food Institute, Technical University of Denmark, Lyngby, Denmark. 6MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
Hypospadias is among the most common congenital malformations with a mean prevalence of 19.9 per 10,000 live births in Europe. The cause of many cases of hypospadias remains unclear but likely results from a combination of genetic susceptibility and environmental factors. Although rodent studies have provided great insights into external genitalia morphogenesis, extrapolations to the human genitals is challenging given significant anatomic and morphogenetic differences. With this study, we provide novel data on the regulation of sex-specific development of the prenatal human genital tubercle (GT). Total RNA from 83 GTs (9-19 gestational weeks (GW), n = 40 males and 43 females) from human fetuses obtained from normally progressing electively-terminated pregnancies (REC 15/NS/0123) were sequenced (NextSeq 500 Illumina). Following raw reads alignment to the human genome (GRCh38), filtration and normalisation, statistically-significant differentially expressed genes (DEGs) were assessed using EdgeR (FDR<0.05). This was followed by ongoing spatial transcriptomics analysis (GeoMx®) based on transversal sections from sex-analogous GT regions. Combining morphometric data from 136 male and 128 female fetuses, GT weights diverged at around 15 GW, 2 weeks later than divergence in anogenital distance, a morphometric readout of androgens action. Samples segregated according to age and sex, accounting for ~51% and 11% of total variation in gene expression, respectively. More transcript changes were sex-related in 2nd than 1st trimesters (1,242 vs 118 DEGs). Males had a larger number of sex-specific DEGs between 1st and 2nd trimesters than females (7,722 vs 6,545 DEGs). Gene Ontology enrichment analyses based on age- (9,163 DEGs) and sex- (1,136 DEGs) related DEGs (filtered with logFC>1) showed significant enrichment of biological processes such as “response to corticosteroid”, “response to steroid hormone”, “extracellular matrix organization” and “epidermis development” (with age only for this last). These data represent early but important steps towards better understanding of sex-dependent human external genitalial development.
Volume 94
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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