Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA.
FEBS J. 2022 May;289(9):2386-2408. doi: 10.1111/febs.15848. Epub 2021 Apr 12.
Gonad development is a highly regulated process that coordinates cell specification and morphogenesis to produce sex-specific organ structures that are required for fertility, such as testicular seminiferous tubules and ovarian follicles. While sex determination occurs within specialized gonadal supporting cells, sexual differentiation is evident throughout the entire organ, including within the interstitial compartment, which contains immune cells and vasculature. While immune and vascular cells have been traditionally appreciated for their supporting roles during tissue growth and homeostasis, an increasing body of evidence supports the idea that these cell types are critical drivers of sexually dimorphic morphogenesis of the gonad. Myeloid immune cells, such as macrophages, are essential for multiple aspects of gonadogenesis and fertility, including for forming and maintaining gonadal vasculature in both sexes at varying stages of life. While vasculature is long known for supporting organ growth and serving as an export mechanism for gonadal sex steroids in utero, it is also an important component of fetal testicular morphogenesis and differentiation; additionally, it is vital for ovarian corpus luteal function and maintenance of pregnancy. These findings point toward a new paradigm in which immune cells and blood vessels are integral components of sexual differentiation and organogenesis. In this review, we discuss the state of the field regarding the diverse roles of immune and vascular cells during organogenesis of the testis and ovary and highlight outstanding questions in the field that could stimulate new research into these previously underappreciated constituents of the gonad.
性腺发育是一个高度调控的过程，它协调细胞特化和形态发生，产生特定性别器官结构，这些结构是生育所必需的，如睾丸曲细精管和卵巢卵泡。虽然性别决定发生在专门的性腺支持细胞内，但性分化在整个器官中都很明显，包括间质腔，其中包含免疫细胞和脉管系统。虽然免疫细胞和血管细胞一直因其在组织生长和稳态中的支持作用而受到传统重视，但越来越多的证据支持这样一种观点，即这些细胞类型是性腺性别二态形态发生的关键驱动因素。髓样免疫细胞，如巨噬细胞，对于性腺发生和生育的多个方面都是必不可少的，包括在生命的不同阶段形成和维持两性的性腺血管系统。虽然血管系统长期以来一直被认为是支持器官生长和作为宫内性腺类固醇的出口机制，但它也是胎儿睾丸形态发生和分化的重要组成部分；此外，它对于卵巢黄体功能和妊娠维持至关重要。这些发现指向一个新的范例，即免疫细胞和血管是性别分化和器官发生的组成部分。在这篇综述中，我们讨论了免疫和血管细胞在睾丸和卵巢发生过程中发挥多种作用的领域现状，并强调了该领域的悬而未决的问题，这些问题可能会激发对这些以前被低估的性腺组成部分的新研究。
