Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats

Mandal, Kunal Kumar; Sarkar, Rajesh; Sharma, Souvik Sen; Jain, Ayushi; Majumdar, Subeer S.

doi:10.1016/j.gene.2017.10.032

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…RA binds to RAR and forms a heterodimer with retinoic X receptors (RXRs) to stimulate the expression of RA-responsive genes directly or indirectly, such as Stra8, SCP3, and PLZF [44,57] (Figure 2). RARα and RARβ are also expressed in Sertoli cells [58,59]. During stages VIII-IX of the seminiferous epithelium, the BTB disassembles to complete the A al -A1 transition, and the level of RA also increases to a peak.…”

Section: The Interactions Between Ra and Btbmentioning

confidence: 99%

Action and Interaction between Retinoic Acid Signaling and Blood–Testis Barrier Function in the Spermatogenesis Cycle

Wang

2022

Cells

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Spermatogenesis is a complex process occurring in mammalian testes, and constant sperm production depends on the exact regulation of the microenvironment in the testes. Many studies have indicated the crucial role of blood–testis barrier (BTB) junctions and retinoic acid (RA) signaling in the spermatogenesis process. The BTB consists of junctions between adjacent Sertoli cells, comprised mainly of tight junctions and gap junctions. In vitamin A-deficient mice, halted spermatogenesis could be rebooted by RA or vitamin A administration, indicating that RA is absolutely required for spermatogenesis. Accordingly, this manuscript will review and discuss how RA and the BTB regulate spermatogenesis and the interaction between RA signaling and BTB function.

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Section: The Interactions Between Ra and Btbmentioning

confidence: 99%

Action and Interaction between Retinoic Acid Signaling and Blood–Testis Barrier Function in the Spermatogenesis Cycle

Wang

2022

Cells

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“…Interestingly, many core mammalian circadian rhythm regulators also oscillate in the soma but exhibit constitutive, nonoscillatory expression in the testes (Alvarez et al, 2008;Kang et al, 2010;Kennaway et al, 2012;Morse et al, 2003). Although the noncircadian roles of these factors in spermatogenesis have not been deeply explored, male mice that are null for the clock gene Bmal1 (Arntl) have fertility defects and are difficult to mate (Alvarez et al, 2008), and depletion of the NHR-23 homolog RORα/NR1F1 in rat Sertoli cells reduces sperm count (Mandal et al, 2018). It remains unclear how these timers have been co-opted to promote spermatogenesis.…”

Section: Circadian Rhythm Regulators In Spermatogenic Tissuesmentioning

confidence: 99%

The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator ofC. elegansspermatogenesis

et al. 2020

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In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulating C. elegans molting, we discovered NHR-23/NR1F1 is also constitutively expressed in developing 1° spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles (MOs) but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.

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“…Retinoid-related nuclear orphan receptor (ROR) family is an essential transcription factors that regulate diverse biological processes including inflammation [ 32 ], lipid homeostasis [ 33 ], circadian rhythms [ 34 ], developmental and cellular metabolism [ 35 ], as well as innate immune response initiation against inflammation [ 20 ]. Expression of RORα nuclear receptors were reported in various tissues including testis, where a relationship between Sertoli cells functions and RORα was detected [ 36 ]. Furthermore, RORα expression and melatonin membrane receptors were recently detected in sheep [ 37 ] and goat [ 38 ] Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging

Sayed

Mokhtar

Fernández-Ortiz

et al. 2020

Aging

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The role of retinoid acid receptor-related orphan receptor alpha (RORα) on male reproductive functions during aging is unclear. Here, we analyze the morphological changes in the testis of both young and aged RORα-deficient mice, with and without melatonin supplementation. Young mutants showed vacuolation, degeneration and pyknosis of spermatogenic epithelium and Sertoli cells. Aged mutants showed atrophy of the seminiferous tubules and absence of mitotic spermatogenic cells. Absence of sperms in many tubules, loss of acrosomal cap, vacuolation and hypertrophy of Sertoli cells were detected in aged mice, with a significant reduction in the number of seminiferous tubules and a significant increase in the number of Leydig cells and telocytes. Repair in seminiferous tubules and interstitial tissues with enhancement of spermatogenesis was observed in melatonin-treated aged mice. Young mutants overexpressed VEGF that was weaker in aged animals and observed only in the spermatocytes, while melatonin increased VEGF expression in spermatocytes and spermatids. Caspase 3 increased in both young and aged mutant mice in all seminiferous tubules and interstitium; caspase 3 immunostaining in seminiferous tubules, however, showed a normal pattern of apoptosis with melatonin supplementation. The present study reports that age-dependent testicular changes in RORα mutant mice were recovered by melatonin treatment.

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Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats

Cited by 11 publications

References 34 publications

Action and Interaction between Retinoic Acid Signaling and Blood–Testis Barrier Function in the Spermatogenesis Cycle

Action and Interaction between Retinoic Acid Signaling and Blood–Testis Barrier Function in the Spermatogenesis Cycle

The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator ofC. elegansspermatogenesis

Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging

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