ESPE Abstracts

Background: The male Hypothalamic-Pituitary-Gonadal (HPG) axis undergoes a transient activity phase during the first months of life with surging serum concentrations of reproductive hormones. Theoretically, the hormonal surge could represent a passive postnatal feedback to the withdrawal from the high sex steroid levels in pregnancy. However, we believe that minipuberty rather represents an active, tightly genetically-regulated biological process. We therefore set out to evaluate whether polygenic scores (PGS) that have been found to predict serum testosterone and SHBG in adult men are also operational in male infancy.

Objective: We investigate PGS of total testosterone (T) and Sex hormone-binding globulin (SHBG) and their impact on sex hormone levels in a deeply phenotyped cohort of male newborns.

Participants & Methods: In a prospective, longitudinal cohort (The COPENHAGEN Minipuberty Study, 2016-2018) we followed 233 healthy, term, singleton newborns (119 boys) from birth onwards with six repeated clinical examinations including blood sampling during a one-year follow-up. Genotyping was performed in 109 boys using a customized Illumina GSA array including HRC imputation, and PGS for SHBG and total testosterone were calculated based data on >200.000 men (Ruth et al. 2020). Linear regression analyses were performed to examine the associations between PGS and the mean age-specific hormone values (mean standard deviation score, SDS) based on longitudinal follow-up throughout the first year of life.

Results: We observed significant associations between T-PGSadult on the one side and mean T-SDSinfancy, mean SHBG-SDSinfancy and mean LH-SDSinfancy on the other side (P= 0.04, 0.003 and 0.02, respectively). SHBG-PGSadult was significantly associated with SHBG-SDSinfancy (p < 0.001) explaining around 19% of the phenotypic variation of SHBG levels in male newborns (r2 = 0.19).

Conclusion: We provide evidence that the genetic architecture underlying circulating testosterone and SHBG levels in adult life are already operational in infancy, which may suggest that minipuberty is a genetically regulated biological process that determine adult reproductive function.