MON-018 Sex Differences In Oxytocin And Oxytocin Receptor Expression In The Mouse Brain: Comprehensive Single Transcript Level Mapping

Abstract Disclosure: G. Pevnev: None. A. Gumerova: None. F. Korkmaz: None. H.S. Kannangara: None. L. Cullen: None. R. Witztum: None. S.L. Sims: None. T. Frolinger: None. O. Moldavski: None. O. Barak: None. G. Burganova: None. D. Lizneva: None. K. Goosens: None. V. Ryu: None. T. Yuen: None. M. Zaidi: None. Oxytocin (OXT) is known for its role in regulating reproductive function and social behavior. However, the neuroanatomical distribution of this hormone and its receptor (OXTR) with respect to sex differences remains incompletely characterized. Therefore, we conducted a comprehensive analysis of Oxt and Oxtr expression, using the highly sensitive RNAscope technology for single-transcript detection, in the brains of adult male and female C57BL/6J mice.All analyses were conducted under blinded conditions to minimize bias, with 10-µm brain sections coded prior to examination. Quantification was performed on every tenth section to avoid double-counting of transcripts. Transcript density was calculated by dividing transcript number by area (µm²) in each neuroanatomical region.Our results demonstrate sexual dimorphism. We found Oxt–positive cells in 22 hypothalamic and forebrain regions in the female, but only 15 such regions in the male mice. In the female hypothalami, numbers of Oxt–positive cells in the medial parvicellular part (PaMP) and medial magnocelluar part (PaMM) paraventricular hypothalamic sub-nuclei and supraoptic nucleus (SO) were significantly greater compared with the male counterpart. In contrast, numbers of Oxt–positive cells in male lateral magnocelluar part (PaLM) of paraventricular sub-nucleus and supraoptic nucleus, retrochiasmatic part (SOR) were markedly greater than those in the female. In the forebrain, numbers of Oxt–positive cells in the medial preoptic area (MPA) and bed nucleus of the stria terminalis, medial division (BSTMV) were significantly greater in the female, whereas numbers of Oxt–positive cells in the lateral preoptic nucleus (LPO) and medial preoptic nucleus, central part (MPOC) were more in the male brain. Likewise, Oxtr density was higher in the third ventricular ependymal region, in the anterolateral and posteromedial (AHiPM) parts of the amygdalohippocampal area and in the forebrain anterior commissure (aci) in males. In contrast, Oxtr transcript density was significantly higher in both anterior and posterior pituitary lobes in female mice.This detailed mapping provides unprecedented insight into sex-specific characteristics of the brain oxytocin system with implications for understanding gender differences in reproductive, social, and feeding behaviors. Presentation: Monday, July 14, 2025