Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Biol Sex Differ. 2022 Oct 11;13(1):57. doi: 10.1186/s13293-022-00467-7.
The pituitary gland regulates essential physiological processes such as growth, pubertal onset, stress response, metabolism, reproduction, and lactation. While sex biases in these functions and hormone production have been described, the underlying identity, temporal deployment, and cell-type specificity of sex-biased pituitary gene regulatory networks are not fully understood.
To capture sex differences in pituitary gene regulation dynamics during postnatal development, we performed 3' untranslated region sequencing and small RNA sequencing to ascertain gene and microRNA expression, respectively, across five postnatal ages (postnatal days 12, 22, 27, 32, 37) that span the pubertal transition in female and male C57BL/6J mouse pituitaries (n = 5-6 biological replicates for each sex at each age).
We observed over 900 instances of sex-biased gene expression and 17 sex-biased microRNAs, with the majority of sex differences occurring with puberty. Using miRNA-gene target interaction databases, we identified 18 sex-biased genes that were putative targets of 5 sex-biased microRNAs. In addition, by combining our bulk RNA-seq with publicly available male and female mouse pituitary single-nuclei RNA-seq data, we obtained evidence that cell-type proportion sex differences exist prior to puberty and persist post-puberty for three major hormone-producing cell types: somatotropes, lactotropes, and gonadotropes. Finally, we identified sex-biased genes in these three pituitary cell types after accounting for cell-type proportion differences between sexes.
Our study reveals the identity and postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary. This work also highlights the importance of considering sex biases in cell-type composition when understanding sex differences in the processes regulated by the pituitary gland.
脑垂体调节着生长、青春期启动、应激反应、代谢、生殖和泌乳等重要的生理过程。虽然这些功能和激素产生存在性别偏向，但性别偏向的脑垂体基因调控网络的潜在特征、时间部署和细胞类型特异性尚未完全了解。
为了捕捉出生后发育过程中脑垂体基因调控的性别差异，我们分别进行了 3'非翻译区测序和小 RNA 测序，以确定五个出生后年龄（出生后第 12、22、27、32 和 37 天）的脑垂体基因和 microRNA 表达，这些年龄跨越了雌性和雄性 C57BL/6J 小鼠脑垂体的青春期过渡（每个性别每个年龄有 5-6 个生物学重复）。
我们观察到超过 900 个性别偏向的基因表达和 17 个性别偏向的 microRNAs，其中大多数性别差异发生在青春期。使用 microRNA-基因靶标相互作用数据库，我们鉴定出 18 个可能是 5 个性别偏向 microRNA 的靶标的性别偏向基因。此外，通过将我们的批量 RNA-seq 与公开的雄性和雌性小鼠脑垂体单细胞 RNA-seq 数据相结合，我们获得了证据表明，在青春期之前就存在细胞类型比例的性别差异，并且在青春期之后，三种主要的激素产生细胞类型（生长激素细胞、催乳素细胞和促性腺激素细胞）仍然存在这种差异。最后，我们在考虑了性别之间细胞类型比例差异后，鉴定了这三种脑垂体细胞类型中的性别偏向基因。
我们的研究揭示了小鼠脑垂体中性别偏向基因表达的特征和出生后的发育轨迹。这项工作还强调了在理解脑垂体调节的过程中的性别差异时，考虑细胞类型组成中的性别偏向的重要性。
