Abstract Body: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in young women. In-utero, children of ~80% of PCOS women in the US are exposed to maternal “hyperandrogenemia and obesity”. It remains unclear whether this exposure affects their cardiovascular (CV) health later in life. Using a well-characterized rat model of maternal PCOS, the hyperandrogenemic obese (HAO) dams, we previously showed that adult male, not female, offspring (HAO_F1) have enhanced blood pressure (BP) response to chronic angiotensin (Ang) II compared to sex-matched control offspring (CON_F1), suggesting their increased risk of later CV disease. Sex steroids have the potential to modulate epigenetics. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) are markers of epigenetic modifications. HDACs have been shown to promote tumor necrosis factor (TNF)-α expression and play a role in Ang II-induced hypertension. The present study was designed to test the hypothesis that male HAO_F1 have intra-renal activation of HDAC and increased TNF-α that could play a role in their Ang II BP response. Methods: At 4 weeks (wks) of age, female SD rats were implanted (s.c.) with either 5α-dihydrotestosterone pellets (7.5 mg/90 d; HAO) or placebo pellets (CON) and mated at 9-12 wks. Offspring were obtained and weaned at 3 wks. Serum testosterone (T; by LC/MS-MS), renal cortical TNF-α (Bioplex) and renal cortical nuclear HDAC and HAT activities (colorimetric assays) were measured in male offspring (1/litter, 16-24 wks, n=5-9). Results: Male HAO_F1 had significantly lower serum T, higher renal cortical HDAC activity and TNF-α (430.2±124 vs 120.6±14 ng/dl, 0.97±0.1 vs 4.51±0.96 OD/min/mg protein and 423.7±47 vs 579.8±47 pg/g tissue, in male CON_F1 vs male HAO_F1, respectively, p<0.05), and no change in their renal cortical HAT activity (vs male CON_F1). Conclusion: Male offspring born to HAO dams develop hypoandrogenemia that is associated with intra-renal activation of HDAC that could be mediating their increased intra-renal inflammation (TNF-α expression) and mediating their exaggerated BP response to Ang II. Future studies will determine the causative relationship between hypoandrogenemia, HDAC activation and TNF-a and their role in the exaggerated pressor response to Ang II in those male offspring. Funding: AHA-24DIVSUP1273026 (JA), NIH-NIGMS P20GM121334 (JFR, NMS), R01HL135089 & R01AG075963 (JFR), AHA-22CDA938320 and 2024 Dean Franklin Award (NMS).