Retinoid-related orphan nuclear receptor alpha (RORα)-deficient mice display morphological testicular defects

Sayed, Ramy K. A.; Mokhtar, Doaa M.; Fernández-Ortiz, Marisol; Escames, Germaine; Acuña-Castroviejo, Darı́o

doi:10.1038/s41374-019-0299-5

Cited by 11 publications

(7 citation statements)

References 65 publications

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“…Toluidine blue is a metachromatic (a pH-dependent dye that stains cell elements a different color from the dye), staining heparin-containing granules purple or red [ 2 , 63 ]. As a simple, non-sensitive chemical, it can be applied to tissues after various methods of fixation and embedding [ 44 , 46 , 47 , 49 , 50 , 51 , 53 , 55 , 57 , 58 , 61 , 62 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ]. However, its major disadvantage is the inability to distinguish immature from mature MCs, which could be done by alcian blue-safranin staining [ 45 , 48 , 67 , 72 , 93 ].…”

Section: Mast Cell Detection Methods In the Mammalian Testis And Epid...mentioning

confidence: 99%

“…Majeed reported finding MCs in the mouse ( Mus musculus ) epididymis but not the testis; however, as in the study analyzing rat testes, without the specification if there might be some MCs in the TA [ 55 ]. Several authors report no MCs in the regular mouse testicular interstitium [ 75 , 76 , 78 , 84 ], respectively analyzed in the neonatal, prepubertal, and adult [ 75 ].…”

Section: Mast Cells In Mammalian Testes and Epididymidesmentioning

confidence: 99%

“…The only example of MC appearance within the seminiferous tubule, among primary spermatocytes near the basement membrane, is observed in retinoid-related orphan nuclear receptor alpha (RORα)-deficient mice, demonstrating disruption of Sertoli–germ cell junctions and showing the necessity for RORα protein in the regulation of testicular structure [ 78 ].…”

Section: Experimental Models Investigating Mast Cells In Mammalian Te...mentioning

confidence: 99%

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Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

Himelreich-Perić

Katušić-Bojanac

Hohšteter

et al. 2022

IJMS

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Mast cells (MCs) are an evolutionary well-conserved type of cells, mediating and modulating allergic responses in innate immunity and tissue remodeling after chronic inflammation. Among other tissues, they inhabit both the testis and epididymis. In the testis, MCs usually appear in the interstitial compartment in humans, but not in other standard experimental models, like rats and mice. MCs seem to be responsible for testicular tissue fibrosis in different causes of infertility. Although experimental animal models follow the effect on MC activation or penetration to the interstitial tissue like in humans to some extent, there is an inconsistency in the available literature regarding experimental design, animal strain, and detection methods used. This comprehensive review offers an insight into the literature on MCs in mammalian testes and epididymides. We aimed to find the most suitable model for research on MC and offer recommendations for future experimental designs. When using in vivo animal models, tunica albuginea incorporation and standard histological assessment need to be included. Domesticated boar strains kept in modified controlled conditions exhibit the highest similarity to the MC distribution in the human testis. 3D testicular models are promising but need further fine-tuning to become a valid model for MC investigation.

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Section: Mast Cell Detection Methods In the Mammalian Testis And Epid...mentioning

confidence: 99%

Section: Mast Cells In Mammalian Testes and Epididymidesmentioning

confidence: 99%

Section: Experimental Models Investigating Mast Cells In Mammalian Te...mentioning

confidence: 99%

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Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

Himelreich-Perić

Katušić-Bojanac

Hohšteter

et al. 2022

IJMS

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“…NR1F1 and NR1F3 regulate angiogenesis via the VEGFA system in several contexts, including retinopathy (Sun et al 2017), ischemia (Besnard et al 2001, cancer (Xiao et al 2015), tissue repair (Ling et al 2017), and testicular development (Sayed et al 2019). Insufficient expression or inhibition of NR1F1 or NR1F3 reduces VEGFA expression and angiogenesis under conditions of reduced oxygen concentration (Sun et al 2015, Suyama et al 2016) and this varies with cell type (Talia et al 2016).…”

Section: Onr1 Family Membersmentioning

confidence: 99%

“…Insufficient expression or inhibition of NR1F1 or NR1F3 reduces VEGFA expression and angiogenesis under conditions of reduced oxygen concentration (Sun et al 2015, Suyama et al 2016) and this varies with cell type (Talia et al 2016). In contrast, deficient expression of NR1F1 is associated with increased VEGFA synthesis in murine testes (Sayed et al 2019). There is a similar low level of NR1F1 expression in the murine hindlimb ischemia model, in which there is a high rate of angiogenesis without an accompanying change in protein concentration of VEGFA (Besnard et al 2001).…”

Section: Onr1 Family Membersmentioning

confidence: 99%

Orphan nuclear receptors in angiogenesis and follicular development

2021

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Orphan nuclear receptors (ONRs) are a subset of the nuclear receptor family that lack known endogenous ligands. Among 48 nuclear receptors identified in humans, 25 are classified as ONRs. They function as transcription factors and control expression of a wide range of genes to regulate metabolism, fertility, immunity, angiogenesis, and many other functions. Angiogenic factors are essential during ovarian follicle development, including follicle growth and ovulation,. Correct development of blood vessels contributes to preantral and antral follicular development, selection of the dominant follicle or follicles, follicular atresia, and ovulation. Although progress has been made in understanding the molecular mechanisms that regulate follicular angiogenesis, the role of ONRs as regulators is not clear. Based on their functions in other tissues, the ONRs NR1D1 (REV-ERBß), NR2C2 (TR4), NR2F2 (COUP-TF-II) and NR3B1, 2, and 3 (ERRα, ERRß and ERRγ) may modulate angiogenesis during antral follicle development. We hypothesize that this is achieved by effects on the expression and function of VEGFA, ANGPT1, THBS1, and soluble VEGFR1. Further, angiogenesis during ovulation is expected to be influenced by ONRs. NR5A2 (LRH-1), which is required for ovulation, regulates angiogenic genes in the ovary, including VEGFA and the upstream regulator of angiogenesis, PGE2. These angiogenic molecules may also be regulated by NR5A1 (SF-1). Evidence from outside the reproductive tract suggests that NR2F2 and NR4A1(NUR77) promote VEGFC and PGF respectively and NR4As (ΝUR77, NOR1) seem to be necessary for the angiogenic effects of VEGFA and PGE2. Together, the data suggest that ONRs are important regulators of follicular angiogenesis.

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