Endocrine Abstracts

Prenatal and postnatal environment can regulate gene expression through multiple epigenetic mechanisms, being DNA methylation among the most relevant. Metabolic and reproductive function may be modified by this mechanism. Sons born to women with PCOS show altered markers of metabolic and reproductive function during childhood and adulthood. However, these functions have not been studied during puberty. The aim of the present study was to assess the global methylation pattern and its possible association with anthropometrics, endocrine and metabolic variables in a cohort of early infants and peripubertal boys born to women with PCOS. Global DNA methylation was measured from blood leucocytes, in 21 sons born to control women (C-Sons) and 15 born to women with PCOS (P-Sons) at early infancy (2-3 months old). In addition, 50 P-Sons (12 prepubertal (Tanner I), 28 pubertal (Tanner II-IV) and 10 late pubertal (Tanner V)) and 61 C-sons (13 prepubertal, 30 pubertal and 18 late pubertal) were studied. Weight, height and waist circumference were determined. A 75-gr oral glucose tolerance test with insulin and glucose measurements was performed. HOMA-IR and ISI composite were calculated. In the fasting sample circulating AMH, 17-OH-Progesterone, androstendione, testosterone, estradiol and lipids were measured. P-Sons showed lower global methylation at early infancy (P=0.027), whereas at pubertal age a higher global methylation was found (P=0.035). No differences were observed during pre and late puberty. At early infancy, no differences were observed in anthropometric variables between C-Sons and P-Sons. In prepubertal age, fasting and 120-min glucose were higher in P-sons compared to C-Sons (P=0.038 and 0.046, respectively). At puberty, waist circumference and androstenedione levels were higher (P=0.032 and 0.006, respectively) and cholesterol tended to be higher (P=0.06) in P-Sons compared to C-Sons. At late puberty, no differences were observed between groups. These results suggest that the methylation pattern can be modified from early infancy to the pubertal age in sons born to PCOS women. During puberty, global methylation increased concomitantly with circulating androstendione levels and waist circumference suggesting that the endocrine and metabolic milieu may be associated with DNA methylation in these boys.