Leydig cell dysfunction is associated with post-transcriptional deregulation of CYP17A1 in men with Sertoli cell-only syndrome

Lardone, María Cecilia; Argandoña, F.; Lorca, Myriam; Piottante, Antonio; Flórez, Martha; Palma, C.; Ebensperger, Mauricio; Castro, Andrea

doi:10.1093/molehr/gay006

Cited by 16 publications

(7 citation statements)

References 36 publications

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“…In this regard, it has been shown that murine Leydig cells deficient in SULT1E1 accumulates cholesterol esters and exhibit steroidogenic impairment with low T production as a result of reduced 17α‐hydroxilase and 17–20 lyase (CYP17A1) expression and activity 12 . Recently, we reported that the immunoreaction of CYP17A1 is decreased in Leydig cells of patients with SCOS, low T/LH ratio, and high intratesticular concentration of E2, suggesting a negative effect of E2 over T biosynthesis 40 …”

Section: Discussionmentioning

confidence: 99%

Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure

et al. 2020

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Background Decreased testosterone (T) to LH ratio and increased 17β‐estradiol (E2) serum concentrations represent a common finding among patients with severe spermatogenic failure, suggesting a concurrent Leydig cell steroidogenic dysfunction. Aromatase overexpression has been associated with increased serum and intratesticular E2 in these patients. However, it is unknown whether the sulfatase pathway contributes to the increased availability of active estrogens in patients with primary spermatogenic failure. Objectives To assess estrogen sulfotransferase (SULT1E1) and steroid sulfatase (STS) mRNA abundance in testicular tissue of patients with Sertoli cell‐only syndrome (SCOS) and normal tissues, its association with serum and intratesticular hormone levels, and to explore the mRNA and protein testicular localization of both enzymes. Materials and Methods Testicular tissues of 23 subjects with SCOS (cases) and 22 patients with obstructive azoospermia and normal spermatogenesis (controls) were obtained after biopsy. SULT1E1 and STS transcripts accumulation was quantified by RT‐qPCR. For mRNA and protein localization, we performed RT‐qPCR in Leydig cell clusters and seminiferous tubules isolated by laser‐capture microdissection and immunofluorescence in testicular tissues. Serum and intratesticular hormones were measured by immunoradiometric assays. Results SULT1E1 mRNA accumulation was similar in both groups. The amount of STS mRNA was higher in cases (p = 0.007) and inversely correlated with T/LH ratio (r = −0.402; p = 0.02). Also, a near significant correlation was observed with intratesticular E2 (r = 0.329, p = 0.057), in agreement with higher intratesticular E2 in cases (p < 0.001). Strong STS immunoreaction was localized in the wall of small blood vessels but not in Leydig cells. Both SULT1E1 and STS mRNA abundance was similar in Leydig cell clusters and the tubular compartment, except for lower SUTL1E1 mRNA in the seminiferous tubules of SCOS patients (p = 0.001). Conclusions Our results suggest that an unbalance of the STS/SULT1E1 pathway contributes to the testicular hyperestrogenic microenvironment in patients with primary spermatogenic failure and Leydig cell dysfunction.

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Section: Discussionmentioning

confidence: 99%

Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure

et al. 2020

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“…Representative images were captured for each sample under the same light intensity and exposure time conditions. The mean-to-area ratio of the integrated optical density parameter (mean IOD) for each subject was used as semiquantitative [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Betaine attenuate chronic restraint stress-induced changes in testicular damage and oxidative stress in male mice

Meng

Peng

et al. 2022

Reprod Biol Endocrinol

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Scope Male fertility and sperm quality are negatively affected by psychological stress. Chronic restraint stress (CRS) is a common psychological stress that has a negative effect on sperm. Betaine (BET), an active ingredient isolated from Lycium barbarum, has anti-oxidant, anti-inflammatory and other pharmacological activities. This study aims to explore whether betaine has a therapeutic effect on sperm deformity and vitality under CRS and its mechanism. Methods and results Chronic restraint stress was induced in 8-week-old male C57BL/6 J mice by fixation for 6 h a day for 35 days. Mice were intraperitoneally injected with betaine (BET) or normal saline (NS) for 14 days. Thirty-five days later, the animals were sacrificed. The results showed that the detrimental effects of CRS on testes as evident by disrupted histoarchitecture, increased oxidative stress, inflammation and apoptosis that compromised male fertility. BET injections can reverse these symptoms. Conclusions BET can improve spermatogenesis dysfunction caused by CRS, which may provide potential dietary guidance. Graphical abstract

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Section: Insl3 Structure Expression Receptor and Rolesmentioning

confidence: 99%

“…35 Further studies utilizing dissection technologies of targeted cells from tissues such as a laser capture microdissection are required to quantitate INSL3 mRNA and peptide accurately at cellular levels. [37][38][39] Ferlin et al 40 have suggested a modulating effect of INSL3 on bone metabolism and linking gene mutations of INSL3 receptors with human osteoporosis. They also demonstrated the role of INSL3 and its receptor system in protein turnover, contributing to muscle wasting in male hypogonadism.…”

Section: Expressioningonadsmentioning

confidence: 99%

“…The authors inferred that the higher testicular INSL3 gene expression in prepubertal dogs might be due to a higher ratio of interstitial space, including Leydig cells, to seminiferous tubules in immature testis compared to fully‐mature testis, where complete spermatogenesis takes place 35 . Further studies utilizing dissection technologies of targeted cells from tissues such as a laser capture microdissection are required to quantitate INSL3 mRNA and peptide accurately at cellular levels 37–39 …”

Section: Insl3 Structure Expression Receptor and Rolesmentioning

confidence: 99%

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Insulin‐like peptide 3 in domestic animals with normal and abnormal reproductive functions, in comparison to rodents and humans

Kawate

2022

Reprod Medicine & Biology

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Background Insulin‐like peptide 3 (INSL3) is a circulating hormone secreted from only testis and ovaries in mammals. Findings on INSL3 have been gathered from subjects with normal and abnormal reproductive statuses, especially rodents and humans. However, little to no review articles focusing on INSL3 in domestic animals exist. Methods The author reviewed the past and recent literature regarding the structure, expression, roles of INSL3 in the reproductive organs, and its circulation under normal and aberrant reproductive conditions in domestic animals in comparison with rodents and humans. Main findings As with humans and rodents, blood INSL3 concentrations rise around puberty in normal male domestic animals and are associated with testicular size. INSL3 levels are acutely upregulated by luteinizing hormone (LH), and the increase is smaller than that of testosterone in male ruminants, whereas the acute regulation of INSL3 by LH does not occur in human men. Dogs with cryptorchidism and bulls with abnormal semen have lowered INSL3 levels. Conclusion The findings regarding INSL3 secretions in male domestic animals with normal and aberrant reproductive functions illustrate similar or dissimilar points to humans and rodents. Data on blood INSL3 levels in normal and abnormal female domestic species are still limited and require further investigation.

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Leydig cell dysfunction is associated with post-transcriptional deregulation of CYP17A1 in men with Sertoli cell-only syndrome

Abstract: This work was supported by the National Fund for Scientific and Technological Development (FONDECYT) of Chile to A.C. [grant number 1120176]. The authors declare no conflict of interest.

Cited by 16 publications

References 36 publications

Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure

Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure

Betaine attenuate chronic restraint stress-induced changes in testicular damage and oxidative stress in male mice

Insulin‐like peptide 3 in domestic animals with normal and abnormal reproductive functions, in comparison to rodents and humans

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