Characterization of the Rete Ovarii: A Secretory Appendage of the Ovary with Potential Roles in Ovarian Function

Core Concepts

The rete ovarii is a complex, multi-regional epithelial structure directly connected to the ovary that plays an important role in ovary development and homeostasis through secretion of proteins into the ovary.

Abstract

The rete ovarii (RO) is an epithelial structure directly connected to the ovary that has been historically overlooked. This study used advanced imaging techniques, genetic mouse models, and proteomic analysis to characterize the development and function of the RO. The RO consists of three distinct regions - the extraovarian rete (EOR), the connecting rete (CR), and the intraovarian rete (IOR). The EOR is a convoluted tubular epithelium with ciliated cells that ends in a distal dilated tip. The CR and IOR have different cellular morphologies. During development, the EOR undergoes rapid expansion and becomes the largest region of the RO by embryonic day 18.5. The RO is highly integrated with the surrounding environment, being tightly associated with vasculature, smooth muscle, neurons, and macrophages. Experiments showed that the fluid contents of the EOR lumen flow towards the ovary, suggesting a secretory function. Mass spectrometry identified secreted proteins in the EOR lumen, including components of the SNARE complex involved in vesicle trafficking and secretion, as well as IGFBP2, which can regulate ovarian function by sequestering IGF1. These findings indicate that the RO is not a vestigial structure, but rather plays an active role in ovary development and homeostasis through secretion of proteins into the ovary. The RO should be considered an integral component of the female reproductive tract that warrants further investigation.

Stats

The fluid within the lumen of the extraovarian rete (EOR) travels towards the ovary. Cells of the EOR express components of the SNARE complex involved in vesicle trafficking and secretion, including STX3 and RAB11. The EOR secretes IGFBP2, which can regulate ovarian function by sequestering IGF1.

Quotes

"The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis." "Our studies reveal that the RO is a continuous structure, surrounded by smooth muscle actin, a dense vascular network, and several macrophage populations. We also show that the RO is directly contacted by neurons." "The enrichment of secretory machinery in RO cells as well as our experimental analysis of directional flow and luminal contents, together suggest that the RO sends material to the ovary."

Key Insights Distilled From

Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

by Anbarci,D. N... at www.biorxiv.org 11-11-2023

https://www.biorxiv.org/content/10.1101/2023.11.08.566085v2

Deeper Inquiries

How do the different regions of the rete ovarii (EOR, CR, IOR) coordinate to regulate ovarian function?

The different regions of the rete ovarii (RO) play distinct roles in regulating ovarian function. The intraovarian rete (IOR) consists of squamous epithelial cells that form a network of thin solid cell cords within the ovary. The extraovarian rete (EOR) is a convoluted tubular structure with ciliated cells that exhibit cellular trafficking capabilities. The connecting rete (CR) consists of pseudo-columnar cells that connect the EOR to the IOR. The coordination between these regions is crucial for maintaining ovarian homeostasis. The EOR, with its ciliated cells and secretory characteristics, is involved in the production and transport of luminal contents towards the ovary. This fluid movement is facilitated by the presence of smooth muscle actin around the EOR, which gains contractility during development. The IOR, on the other hand, forms a network within the ovary and may serve as a progenitor for supporting cells of the gonad. The CR acts as a bridge between the EOR and IOR, gradually acquiring tubular epithelial characteristics by birth. Overall, the coordinated function of these regions allows for the exchange of signals, secreted factors, and potentially sensory information between the RO and the ovary, contributing to the regulation of ovarian development and function.

How do the different regions of the rete ovarii (EOR, CR, IOR) coordinate to regulate ovarian function?

The rete ovarii (RO) is a complex structure that secretes proteins potentially important for ovarian function. Apart from the proteins mentioned in the study, there could be other secreted factors from the RO that influence ovarian development, folliculogenesis, or steroidogenesis. Some of these factors may include growth factors, cytokines, extracellular matrix proteins, and signaling molecules. For example, growth factors like insulin-like growth factors (IGFs) and transforming growth factors (TGFs) are known to play crucial roles in ovarian function. These factors can regulate cell proliferation, differentiation, and survival in the ovary. Cytokines, such as interleukins and tumor necrosis factor, may also modulate immune responses and tissue remodeling in the ovary. Extracellular matrix proteins like collagen and fibronectin provide structural support and influence cell behavior in the ovarian microenvironment. Signaling molecules like Wnt, Notch, and Hedgehog pathways are involved in cell-cell communication and tissue patterning during ovarian development. The secreted factors from the RO likely interact with the ovarian cells, including granulosa cells, theca cells, and oocytes, to regulate various processes such as follicle growth, ovulation, and hormone production. Understanding the full spectrum of secreted factors from the RO and their effects on ovarian function could provide valuable insights into reproductive health and potential therapeutic targets for ovarian disorders.

Could disruptions in rete ovarii structure or function contribute to ovarian pathologies such as polycystic ovary syndrome or ovarian cancer?

Disruptions in rete ovarii structure or function could potentially contribute to ovarian pathologies such as polycystic ovary syndrome (PCOS) or ovarian cancer. PCOS is a common endocrine disorder characterized by hormonal imbalances, ovarian cysts, and irregular menstrual cycles. The RO, with its role in ovarian development and homeostasis, could be implicated in the pathogenesis of PCOS. In PCOS, abnormalities in folliculogenesis, steroidogenesis, and ovulation are observed, which could be influenced by dysregulation in the secretory function of the RO. If the RO fails to properly secrete factors that regulate ovarian function, it could disrupt the normal hormonal balance and follicle development, contributing to the symptoms of PCOS. Similarly, disruptions in the RO could also play a role in ovarian cancer development. Ovarian cancer is a heterogeneous disease with various subtypes, and alterations in the microenvironment and signaling pathways within the ovary are known to contribute to tumorigenesis. The secreted proteins from the RO, if dysregulated, could potentially create a pro-tumorigenic environment in the ovary, promoting cell proliferation, angiogenesis, and metastasis. Further research into the specific proteins and signaling pathways involved in the function of the RO, as well as their potential dysregulation in ovarian pathologies, could provide valuable insights into the mechanisms underlying these conditions and lead to the development of targeted therapies.