Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii
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Curated by eLife
Evaluation Summary:
This work describes mouse ovary morphogenesis from E14.5 to birth using recently developed methods combining CUBIC and iDISCO and optimized 3D imaging using light sheet microscopy. The manuscript is of interest to all developmental biologists as it will serve as a reference to whole embryo morphogenesis, in particular vertebrate ovary morphogenetic processes.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Abstract
Morphogenetic events during the 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 (RO) elaborated into a convoluted tubular structure extending from the ovary into the ovarian capsule. Using genetic mouse models in which the oviduct and RO 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.
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Evaluation Summary:
This work describes mouse ovary morphogenesis from E14.5 to birth using recently developed methods combining CUBIC and iDISCO and optimized 3D imaging using light sheet microscopy. The manuscript is of interest to all developmental biologists as it will serve as a reference to whole embryo morphogenesis, in particular vertebrate ovary morphogenetic processes.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Reviewer #1 (Public Review):
McKey et al. describe mouse ovary morphogenesis in detail using state-of-the-art microscopy and imaging techniques. The authors visualize fetal and perinatal ovary in situ in the context of the whole embryo. They find that three tissues closely associated with the ovary: the ovarian ligaments, the Müllerian duct and the rete ovarii dynamically correlate with ovary morphogenesis. They also find that different combinations of Pax2 and Pax8 deletion alleles affect the oviduct and/or regions of the rete ovarii differentially, and lead to disruptions in ovary morphogenesis.
Strengths:
The detailed analysis and images. The analysis of ovary morphogenesis in the context of surrounding tissues.Weaknesses:
The molecular analysis of mutant conditions would gain with more detailed cellular observations. -
Reviewer #2 (Public Review):
Overall, I don't have any major criticisms for this study. We see here an exceptional work in terms of quantity and quality of data provided to support the hypotheses made by the authors. I am convinced that this study will serve as a reference in the future for scientists working on the establishment of the ovarian tract at the fetal level. The early period of determination of the ovary is now relatively understood in mice, but everything that happens around this organ after E14.5 is poorly documented. Here the authors propose a particularly attractive model on the relationship between morphological change and the regionalization of this organ in the medulla and cortical regions. Clearly this study opens up new lines of research to understand this process which will govern post-natal ovarian physiology.
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