Hormonal regulation of c-KIT receptor and its ligand: implications for human infertility?

Figueira, Marília I.; Cardoso, Henrique J.; Correia, Sara; Maia, Cláudio J.; Socorro, Sílvia

doi:10.1016/j.proghi.2014.09.001

Cited by 21 publications

(35 citation statements)

References 136 publications

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“…Estrogens also suppress c-KIT (type III receptor tyrosine kinase) expression in seminiferous tubules of the testis and simultaneously decrease proliferation and increase apoptosis in germ cells. Therefore, an increased estrogen concentration results in male infertility and c-KIT expression (Figueira et al, 2014). As described in the present study, decreased testis weight was correlated with atrophied seminiferous tubular diameter at high PPT concentrations.…”

Section: Discussionsupporting

confidence: 80%

Effects of Short-Term Treatment with Estrogen Receptor Agonist on Morphological Changes in Reproductive Organs of Adult Male Mice

Choi

Lee

et al. 2016

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Male reproductive organs are strongly affected by estrogen signaling mediated via the estrogen receptor. In this study, propyl pyrazole triol (PPT), an estrogen receptor alpha agonist, was subcutaneously injected in adult male mice every 2 days for a total duration of 8, 16, or 24 days. Histological changes in the reproductive organs, including the testes, efferent ductules, and epididymides, were observed. The weight of the reproductive organs decreased in the PPT group. In addition, the diameter of the seminiferous tubules decreased in the PPT group compared with the control group. The epithelial cell height decreased in the initial segment of the epididymis, whereas the luminal diameter increased in the efferent ductules of the PPT group. PPT induced irregular morphology of stereocilia in the luminal region of the initial segment. Therefore, PPT treatment at high concentrations had inhibitory effects in the reproductive organs of adult male mice. These findings suggest that short-term treatment with estrogen receptor agonist causes histological changes in the testes, efferent ductules, and epididymis, which are similar to those caused by estrogen receptor antagonist treatment. Therefore, the estrogen receptor may have functional roles in male reproductive organs, implying that treatment with an estrogen receptor agonist can affect male fertility.

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Section: Discussionsupporting

confidence: 80%

Effects of Short-Term Treatment with Estrogen Receptor Agonist on Morphological Changes in Reproductive Organs of Adult Male Mice

Choi

Lee

et al. 2016

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“…It is speculated that abnormal levels of androgens deregulate the expression of c‐Kit and stem cell factor (SCF), which may be linked with the aetiology of infertility (Figueira et al . ). The SCF/c‐Kit system determines the survival of germ cells (Yan et al .…”

Section: Discussionmentioning

confidence: 97%

“…c-Kit is a type III receptor of the tyrosine kinase family (Figueira et al 2014). Together with its ligand stem cell factor (SCF), c-Kit is a key controlling receptor for a number of cell types, including haematopoietic stem cells, melanocytes, mast cells and germ cells (Ronnstrand 2004).…”

mentioning

confidence: 99%

Efficacy of naringenin against permethrin‐induced testicular toxicity in rats

Mostafa

El-Baset

Kattaia

et al. 2016

Int J Experimental Path

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SUMMARYPermethrin (PM), a synthetic pyrethroid insecticide, has broad toxicity spectra. We aimed to investigate the effects of PM on the testes of adult albino rats, examine the recovery response and evaluate the efficacy of naringenin (NG) supplementation. Adult male albino rats were randomly assigned to five groups of six each: control, NG (50 mg/kg), PM (70 mg/kg), recovery (after subsequent withdrawal of PM) and NG-PM group. All treatments were given by oral gavage for 6 weeks and another 3 weeks for the recovery group. At the time of sacrifice, each testis was weighed. Biochemical analysis of epididymal sperm count and serum testosterone level was performed. Testes were processed for histological, ultrastructural and c-Kit immunohistochemical study. PM toxicity was evidenced by a highly significant decrease in testicular weight, epididymal sperm count and serum testosterone level compared to control. Furthermore, testicular structure abnormalities and reduced c-Kit immunoreactions were observed. Stoppage of PM in the recovery group partially reversed PMinduced changes. There was a mild decrease in testicular weight and biochemical parameters compared to control. The structure of seminiferous tubules was partially retained. The NG-PM group showed an overall improvement in testicular weight and biochemical alterations which were confirmed by light and electron microscopic examination. In conclusion, PM induced testicular toxicity, which was ameliorated by NG co-administration. However, stoppage of PM exposure was associated with partial recovery.

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“…The mutation in tyrosine receptor kinase, KIT, mostly reported in cancer; however, several single-nucleotide polymorphisms (SNPs) in this gene reported that were associated with oligospermia and azoospermia (Cheng, Chen, Liu, Pu, & Zhou Cun, 2013;Galan et al, 2006). The KIT protein and its ligand stem cell factor (SCF) involved in growth and survival of germinal cells and alteration in the expression of these genes lead to infertility (Correia, Alves, Cavaco, Oliveira, & Socorro, 2014;Figueira, Cardoso, Correia, Maia, & Socorro, 2014) maybe through imbalance between death and survival (Cardoso, Figueira, Correia, Vaz, & Socorro, 2014). PARK7 gene encodes DJ-1 protein that expressed ubiquitously; nonetheless, its expression specifically high in testis (Nagakubo et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

et al. 2020

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Asthenozoospermia (AZS), which characterised by reduced forward sperm motility, is a common cause of male infertility. Recently, mitochondrial dysfunction reported in AZS men came to attention for finding the molecular aetiology of AZS. Mitochondria‐related microRNAs (miRNAs) are the most important regulators of mitochondrial function through post‐transcriptionally modulation of gene expression. Therefore, this study aims to evaluate the expression of four recently reported mitochondrial‐related miRNAs (miR‐4485‐3p/4484/4461 and 4463) in the sperm sample of asthenozoospermic men. RNA was extracted from spermatozoa of 74 volunteers (39 patients with idiopathic AZS and 35 controls with normal fertility), and relative gene expression analysis was performed by quantitative PCR. We used SNORD48 as a normaliser gene, and quantification was calculated by 2−ΔΔCt method. The expression of miR‐4484 and miR‐4461 was not detected in the spermatozoa of cases and controls. However, miR‐4485‐3p (p = .006) was significantly downregulated in the AZS men compared with the controls, but the miR‐4463 expression was not significantly different between the two groups (p = .5). Bioinformatic analysis identified three target genes for miR‐4485‐3p (DNAH1, KIT and PARK7) that are related to male infertility. In conclusion, the downregulation of miR‐4485‐3p was associated with idiopathic AZS, which could be a molecular link between mitochondrial dysfunction and AZS.

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Hormonal regulation of c-KIT receptor and its ligand: implications for human infertility?

Cited by 21 publications

References 136 publications

Effects of Short-Term Treatment with Estrogen Receptor Agonist on Morphological Changes in Reproductive Organs of Adult Male Mice

Effects of Short-Term Treatment with Estrogen Receptor Agonist on Morphological Changes in Reproductive Organs of Adult Male Mice

Efficacy of naringenin against permethrin‐induced testicular toxicity in rats

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

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