VCAM1 Is Induced in Ovarian Theca and Stromal Cells in a Mouse Model of Androgen Excess

Candelaria, Nicholes R.; Padmanabhan, Achuth; Stossi, Fabio; Ljungberg, M. Cecilia; Shelly, Katharine E.; Pew, Braden; Solis, Minerva; Rossano, Ayane M.; McAllister, Jan M.; Wu, Sheng; Richards, Jo Anne S.

doi:10.1210/en.2018-00731

Cited by 24 publications

(23 citation statements)

References 62 publications

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“…Additionally, they found that transcripts for certain steroidogenic enzymes (STAR, CYP11A1, and HSD3B) were much less abundant in the in vitro isolated stromal cells than in theca cells, with the exception of STAR which had more transcript abundance in stromal cells than in fibroblasts (Jabara et al 2003). In contrast, localization of CYP17A1 shifted from exclusively the theca interna in control mice to patches in the interstitial stroma in DHT-treated mice, supporting a potential role for the stroma in androgen production following certain perturbations (Candelaria et al 2019). Singlecell RNA sequencing studies have also demonstrated subpopulations of stromal cells expressing CYP17A1 and STAR (Wagner et al 2020, Wang et al 2020.…”

Section: R33mentioning

confidence: 89%

“…Mice treated with dihydrotestosterone (DHT) also demonstrated stromal changes, including less dense, hyperplastic, and lipidfilled stroma when compared to age-matched controls. These mice also had an overexpression of multiple genes in the mechanically separated stroma between controls and DHT-treated mice (Candelaria et al 2019). This included increased Vcam1 expression (which may impact vascular and immune responses) in thecal and stromal cells, while theca-specific androgen H M Kinnear and others…”

Section: Pathological Ovarian Stromal Changes: Polycystic Ovary Syndrmentioning

confidence: 97%

“…ThARKO mice were also shown to retain much of their reproductive function, including cyclicity and fertility, as compared to controls when treated with DHT (Ma et al 2017). For mice with DHT-induced stromal changes, superovulation rescued at least some of the abnormal stromal morphology (Candelaria et al 2019).…”

Section: R34mentioning

confidence: 99%

“…Reproduction (2020) 160 R25-R39 receptor knockout mice (ThARKO, Cyp17a1-iCre, AR f/f mice) demonstrated a lack of DHT-induced Vcam1 elevation (Richards et al 2018, Candelaria et al 2019. ThARKO mice were also shown to retain much of their reproductive function, including cyclicity and fertility, as compared to controls when treated with DHT (Ma et al 2017).…”

Section: R34mentioning

confidence: 99%

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The ovarian stroma as a new frontier

et al. 2020

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Historically, research in ovarian biology has focused on folliculogenesis, but recently the ovarian stroma has become an exciting new frontier for research, holding critical keys to understanding complex ovarian dynamics. Ovarian follicles, which are the functional units of the ovary, comprise the ovarian parenchyma, while the ovarian stroma thus refers to the inverse, or the components of the ovary that are not ovarian follicles. The ovarian stroma includes more general components such as immune cells, blood vessels, nerves, and lymphatic vessels, as well as ovary-specific components including ovarian surface epithelium, tunica albuginea, intraovarian rete ovarii, hilar cells, stem cells, and a majority of incompletely characterized stromal cells including the fibroblast-like, spindle-shaped, and interstitial cells. The stroma also includes ovarian extracellular matrix components. This review combines foundational and emerging scholarship regarding the structures and roles of the different components of the ovarian stroma in normal physiology. This is followed by a discussion of key areas for further research regarding the ovarian stroma, including elucidating theca cell origins, understanding stromal cell hormone production and responsiveness, investigating pathological conditions such as polycystic ovary syndrome (PCOS), developing artificial ovary technology, and using technological advances to further delineate the multiple stromal cell types.

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Section: R33mentioning

confidence: 89%

Section: Pathological Ovarian Stromal Changes: Polycystic Ovary Syndrmentioning

confidence: 97%

Section: R34mentioning

confidence: 99%

Section: R34mentioning

confidence: 99%

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The ovarian stroma as a new frontier

et al. 2020

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“…Expression of this gene is most often associated with activation of immune responses during inflammation in endothelial cells [44]. VCAM1 is an interstitial progenitor testis cells marker and is present at high levels in adult Leydig cells [45]. In theca cells, increase in VCAM1 expression is preceded by activation of the androgen receptor which indirectly results in change of the expression and/or activity of the NR2F2 (nuclear receptor subfamily 2, group F, member 2) gene.…”

Section: Discussionmentioning

confidence: 99%

Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging—A Study of New Molecular Markers

Chermuła

Kranc

Jopek

et al. 2020

Cells

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In the ovarian follicle, maturation of the oocyte increases in the presence of somatic cells called cumulus cells (CCs). These cells form a direct barrier between the oocyte and external environment. Thanks to bidirectional communication, they have a direct impact on the oocyte, its quality and development potential. Understanding the genetic profile of CCs appears to be important in elucidating the physiology of oocytes. Long-term in vitro culture of CCs collected from patients undergoing controlled ovarian stimulation during in vitro fertilization procedure was conducted. Using microarray expression analysis, transcript levels were assessed on day 1, 7, 15, and 30 of culture. Apoptosis and aging of CCs strictly influence oocyte quality and subsequently the outcome of assisted reproductive technologies (ART). Thus, particular attention was paid to the analysis of genes involved in programmed cell death, aging, and apoptosis. Due to the detailed level of expression analysis of each of the 133 analyzed genes, three groups were selected: first with significantly decreased expression during the culture; second with the statistically lowest increase in expression; and third with the highest significant increase in expression. COL3A1, SFRP4, CTGF, HTR2B, VCAM1, TNFRSF11B genes, belonging to the third group, were identified as potential carriers of information on oocyte quality.

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