Fig 1.
Anatomy and immune landscape of the female reproductive tract (FRT) in humans and mice.
The FRT in both species includes the ovaries, oviducts/fallopian tubes, uterus, cervix (endocervix and ectocervix), and vagina. Notable anatomical differences exist where humans have a single, pyriform uterus connected to the ovaries by long fallopian tubes, whereas mice possess a bicornuate uterus (two uterine horns) with short oviducts. In both species, the upper FRT is lined by a monolayer of columnar epithelial cells, which transitions at the cervical junction to stratified, squamous, non-keratinised epithelium in the lower FRT. Across both regions, a variety of innate and adaptive immune cells contribute to immune surveillance while preserving tissue homeostasis [7,40,41]. Additional defence mechanisms, including mucus, antimicrobial peptides (AMPs), and resident microbiota, support this immune balance. Created in BioRender. Shorthouse, O. (2025) https://BioRender.com/1xl8eue.
Fig 2.
Disruption of gut-brain FRT crosstalk during inflammation or infection.
Diagram illustrating potential routes of communication between the gut, brain and FRT that may influence the FRT immune landscape. Cytokines and gut-derived metabolites can signal to the brain, potentially suppressing hypothalamic gonadotropin-releasing hormone (GnRH) production and downstream luteinising hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary gland [34]. This suppression leads to dysregulated sex steroid hormone levels, which will impact the FRT immune landscape and reproductive function [36]. In parallel, gut-derived metabolites and cytokines may directly act on the FRT to alter its function [30]. Conversely, FRT-derived metabolites may feed back to modulate gut homeostasis [32]. Created in BioRender. Shorthouse, O. (2025) https://BioRender.com/8gd9qy3.