Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii

Abstract

Morphogenetic events during development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii elaborated into a convoluted tubular structure extending from the ovary into the ovarian capsule. Using genetic mouse models in which the oviduct and rete ovarii are perturbed, we found the oviduct is required for ovary encapsulation. This study reveals novel relationships among the ovary and surrounding tissues and paves the way for functional investigation of the relationship between architecture and differentiation of the mammalian ovary.

Rediscovering theRete Ovarii: a secreting auxiliary structure to the ovary

“…Recently we found that the entire RO expresses PAX8+, which is usually considered a marker of urogenital epithelial identity. We also showed that the IOR contained PAX8+/FOXL2+ cells and that the EOR was KRT8+ at E17.5 (McKey et al, 2022). In this study we further characterized KRT8 and E-Cadherin expression throughout RO development as the CR acquires epithelial characteristics.…”

“…Although the RO has been proposed to be the female homologue of the rete testis (Wenzel and Odend'hal, 1985), our recent work revealed that it is more complex (McKey et al, 2022). The RO is composed of three distinct regions: (1) the extraovarian rete (EOR) which consists of columnar epithelial cells that create a single convoluted tubule structure ending in a blind distal dilated tip (DDT), (2) the connecting rete (CR) which consists of pseudo-columnar cells; and (3) the intraovarian rete (IOR) which consists of squamous epithelial cells that branch and form a fine network of thin solid cell cords approximately 1-3 cells thick (Byskov and Lintern-Moore, 1973;McKey et al, 2022). It was previously shown that the RO consists of ciliated and nonciliated cells rich in apical microvilli and mitochondria (Czernobilsky et al, 1985).…”

“…The RO was rediscovered and highlighted in our recent study (McKey et al, 2022), where we used confocal and lightsheet imaging of whole ovaries to study the integration of ovary morphogenesis with the development of surrounding tissues, including the RO. Recently, the IOR has gained attention as a newly described progenitor for supporting cells of the murine gonad (Mayère et al, 2022).…”

Transcriptome analysis of the mouse fetal and adult rete ovarii and surrounding tissues

“…The rete ovarii (RO) is an epithelial structure that develops in close association with the ovary during fetal life and remains in adulthood in mammals (1,2). Despite the significant architecture of this ovarian appendage, and the fact that it is highly conserved in mammals (3)(4)(5), the function of the RO has not yet been determined, and it has disappeared from recent descriptions of female reproductive anatomy.…”

“…The EOR begins to develop from the mesonephric tubules as a blind tubular epithelium that connects to the CR starting around E14.5 (2). In the adult, the IOR has regressed to a smaller population of cells within the ovary, while the EOR has significantly expanded into a single convoluted tubule ending in a blind distal dilated tip (2,10). The RO is in a unique location between the ovary and extraovarian milieu, where vascular and neuronal networks enter the ovary.…”