Oxytocin (OT) is a developmentally important neuropeptide recognized to play a dominant role in social functioning and stress‐related behaviors, in a sex‐dependent manner. Nonetheless, the underlining factors driving OT and OT receptor (OTR) early brain development remain unclear. Recent evidence highlight the critical influence of gut microbiota and its bidirectional interaction with the brain on neurodevelopment via the gut microbiota‐brain axis. Therefore, we aimed to determine the impact of gut microbiota on the OTR system of the rat brain at different developmental stages in a pilot study. Quantitative OTR [¹²⁵I]‐OVTA autoradiographic binding was carried out in the forebrain of male and female conventional (CON) and germ‐free (GF) rats at postnatal days (PND) 8, 22, and 116–150. OTR binding was also assessed in the eyes of PND 1 and PND 4 GF female rats. Significant “microbiota × sex × region” interaction and age‐dependent effects on OTR binding were demonstrated. Microbiota status influenced OTR levels in males but not females with higher levels of OTR observed in GF versus CON rats in the cingulate, prelimbic, and lateral/medial/ventral orbital cortex, and septum across all age groups, while sex differences were observed in GF, but not in CON rats. Interestingly, OTRs present in the eyes of CON rats were abolished in GF rats. This is the first study to uncover a sex‐specific role of gut microbiota on the central OTR system, which may have implications in understanding the developmental neuroadaptations critical for behavioral regulation and the etiology of certain neurodevelopmental disorders.

中文翻译：

---

肠道菌群对中枢催产素受体的区域特异性性别调节：一项个体发生研究

催产素 (OT) 是一种发育上重要的神经肽，被认为在社会功能和压力相关行为中起主导作用，并以性别依赖的方式。尽管如此，驱动 OT 和 OT 受体 (OTR) 早期大脑发育的重要因素仍不清楚。最近的证据强调了肠道菌群及其与大脑的双向相互作用通过肠道菌群-大脑轴对神经发育的关键影响。因此，我们的目的是在一项初步研究中确定肠道微生物群对不同发育阶段大鼠大脑 OTR 系统的影响。定量OTR [ ¹²⁵在出生后第 8、22 和 116-150 天 (PND) 的雄性和雌性常规 (CON) 和无菌 (GF) 大鼠的前脑中进行了 I]-OVTA 放射自显影结合。在 PND 1 和 PND 4 GF 雌性大鼠的眼睛中也评估了 OTR 结合。证明了显着的“微生物群 × 性别 × 区域”相互作用和年龄依赖性对 OTR 结合的影响。微生物群状态影响雄性而非雌性的 OTR 水平，在所有年龄组的扣带回、前肢和外侧/内侧/腹侧眶皮层和隔膜中，在 GF 和 CON 大鼠中观察到的 OTR 水平更高，而在 GF 中观察到性别差异，但不是在 CON 大鼠中。有趣的是，存在于 CON 大鼠眼中的 OTR 在 GF 大鼠中被废除。这是第一项揭示肠道微生物群对中央 OTR 系统的性别特异性作用的研究，