Follicle dynamics and global organization in the intact mouse ovary

Faire, Mehlika B.; Skillern, A.; Arora, Ritu; Nguyen, Daniel H.; Wang, Jason; Chamberlain, Chester E.; German, Michael S.; Fung, Jennifer C.; Laird, Diana J.

doi:10.1016/j.ydbio.2015.04.006

Cited by 37 publications

(40 citation statements)

References 45 publications

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“…Findings of increases in percentages of primordial and primary follicles during senescence further suggested an age-related decline in follicle activation and development. Our findings related to age-dependent decline of number of primordial follicles are comparable to prior estimates of primordial follicle loss using a stereological method23 and whole mount immunofluorescence analyses7. For intact ovarian imaging, other methods such as X-ray imaging and ultrasound imaging have been developed in rodents2425.…”

Section: Discussionsupporting

confidence: 83%

“…Most traditional histological analyses deal with limited information regarding interrelationships among follicles and corpora lutea due to uncharacterized three-dimensional (3D) architecture. Based on nuclear volume of the oocyte as an indicator of follicles, a recent whole mount immunofluorescence 3D imaging study begun to provide follicle dynamics from neonate to adult mice7. However, there is no analysis on follicular somatic cells together with oocytes in 3D architecture.…”

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confidence: 99%

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CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions

Feng

Cui

et al. 2017

Sci Rep

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Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles. Follicle development from primordial to preovulatory stage was characterized by 3 × 105-fold increases in volume, decreases in roundness, and decreased clustering of same stage follicles. Construction of follicle-vasculature relationship maps indicated age- and gonadotropin-dependent increases in vasculature and branching surrounding follicles. Heterozygous mutant mice with deletion of hypoxia-response element in the vascular endothelial growth factor A (VEGFA) promoter showed defective ovarian vasculature and decreased ovulatory responses. Unilateral intrabursal injection of axitinib, an inhibitor of VEGF receptors, retarded neo-angiogenesis that was associated with defective ovulation in treated ovaries. Our approach uncovers unique features of ovarian architecture and essential roles of vasculature in organizing follicles to allow future studies on normal and diseased human ovaries. Similar approaches could also reveal roles of neo-angiogenesis during embryonic development and tumorigenesis.

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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions

Feng

Cui

et al. 2017

Sci Rep

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“…We used whole-mount immunofluorescence and confocal imaging (Faire et al, 2015) to visualize and characterize changes in the mouse endometrium from fertilization through implantation. Luminal and glandular epithelium in the uterus were identified using the epithelial marker E-cadherin (E-CAD) (Reardon et al, 2012), whereas FOXA2 (Besnard et al, 2004) was used to distinguish glandular epithelium throughout the length and depth of the uterine horn ( Fig.…”

Section: Results and Discussion Confocal Imaging Of The Mouse And Hummentioning

confidence: 99%

Insights from imaging the implanting embryo and the uterine environment in three dimensions

et al. 2016

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Although much is known about the embryo during implantation, the architecture of the uterine environment in which the early embryo develops is not well understood. We employed confocal imaging in combination with 3D analysis to identify and quantify dynamic changes to the luminal structure of murine uterus in preparation for implantation. When applied to mouse mutants with known implantation defects, this method detected striking peri-implantation abnormalities in uterine morphology that cannot be visualized by histology. We revealed 3D organization of uterine glands and found that they undergo a stereotypical reorientation concurrent with implantation. Furthermore, we extended this technique to generate a 3D rendering of the cycling human endometrium. Analyzing the uterine and embryo structure in 3D for different genetic mutants and pathological conditions will help uncover novel molecular pathways and global structural changes that contribute to successful implantation of an embryo.

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“…For whole-mount immunofluorescence, gonads were fixed in DMSO: Methanol (1:4) and stained as described (Faire et al, 2015).…”

Section: Immunohistochemistry and Immunofluorescencementioning

confidence: 99%

Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary

Arora

Ross

Cantu

et al. 2016

Journal of Cell Science

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Mouse ovarian germ cells enter meiosis in a wave that propagates from anterior to posterior, but little is known about contribution of germ cells to initiation or propagation of meiosis. In a Ror2 mutant with diminished germ cell number and migration, we find that overall timing of meiotic initiation is delayed at the population level. We use chemotherapeutic depletion to exclude a profoundly reduced number of germ cells as a cause for meiotic delay. We rule out sex reversal or failure to specify somatic support cells as contributors to the meiotic phenotype. Instead, we find that anomalies in the distribution of germ cells as well as gonad shape in mutants contribute to aberrant initiation of meiosis. Our analysis supports a model of meiotic initiation via diffusible signal(s), excludes a role for germ cells in commencing the meiotic wave and furnishes the first phenotypic demonstration of the wave of meiotic entry. Finally, our studies underscore the importance of considering germ cell migration defects while studying meiosis to discern secondary effects resulting from positioning versus primary meiotic entry phenotypes.

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Follicle dynamics and global organization in the intact mouse ovary

Cited by 37 publications

References 45 publications

CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions

CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions

Insights from imaging the implanting embryo and the uterine environment in three dimensions

Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary

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