scholarly journals Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 447-456 ◽  
Author(s):  
S S Laurentino ◽  
S Correia ◽  
J E Cavaco ◽  
P F Oliveira ◽  
L Rato ◽  
...  

Regucalcin (RGN) is a calcium (Ca2+)-binding protein which regulates intracellular Ca2+homeostasis by modulating the activity of enzymes regulating Ca2+concentration and enhancing Ca2+-pumping activity. Several studies have described the pivotal role of proper Ca2+homeostasis regulation to spermatogenesis and male fertility. Recently,RGNwas identified as a sex steroid-regulated gene in prostate and breast; however, a possible role of RGN in spermatogenesis has not been examined. In this study, the expression and localization of RGN in rat and human testis, and other rat reproductive tissues was analyzed. Moreover, we studied whether RGN protein was present in seminiferous tubule fluid (STF). Finally, we examined the effect of 5α-dihydrotestosterone (DHT) on the expression ofRgnmRNA in rat seminiferous tubules (SeT) culturedex vivo. The results presented in this study show that RGN is expressed in Leydig and Sertoli cells, as well as in all types of germ cells of both rat and human testis. RGN is also expressed in rat prostate, epididymis, and seminal vesicles. Moreover, RGN protein is present in rat STF. The results also demonstrate thatRgnexpression is age dependent in rat testis, and is upregulated by the non-aromatizable androgen DHT in rat SeT culturedex vivo. Taken together, these findings indicate thatRgnis a novel androgen-target gene in rat testis and that it may have a role in male reproductive function, particularly in the control of spermatogenesis.

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3390-3402 ◽  
Author(s):  
J. E. Caminos ◽  
R. Nogueiras ◽  
F. Gaytán ◽  
R. Pineda ◽  
C. R. González ◽  
...  

Adiponectin is an adipocyte hormone, with relevant roles in lipid metabolism and glucose homeostasis, recently involved in the control of different endocrine organs, such as the placenta, pituitary and, likely, the ovary. However, whether as described previously for other adipokines, such as leptin and resistin, adiponectin is expressed and/or conducts biological actions in the male gonad remains unexplored. In this study, we provide compelling evidence for the expression, putative hormonal regulation, and direct effects of adiponectin in the rat testis. Testicular expression of adiponectin was demonstrated along postnatal development, with a distinctive pattern of RNA transcripts and discernible protein levels that appeared mostly located at interstitial Leydig cells. Testicular levels of adiponectin mRNA were marginally regulated by pituitary gonadotropins but overtly modulated by metabolic signals, such as glucocorticoids, thyroxine, and peroxisome proliferator-activated receptor-γ, whose effects were partially different from those on circulating levels of adiponectin. In addition, expression of the genes encoding adiponectin receptor (AdipoR)-1 and AdipoR2 was detected in the rat testis, with developmental changes and gonadotropin regulation for AdipoR2 mRNA, and prominent levels of AdipoR1 in seminiferous tubules. Moreover, recombinant adiponectin significantly inhibited basal and human choriogonadotropin-stimulated testosterone secretion ex vivo, whereas it failed to change relative levels of several Sertoli cell-expressed mRNAs, such as stem cell factor and anti-Müllerian hormone. In summary, our data are the first to document the expression, regulation and functional role of adiponectin in the rat testis. Taken together with its recently reported expression in the ovary and its effects on LH secretion and ovarian steroidogenesis, these results further substantiate a multifaceted role of adiponectin in the control of the reproductive axis, which might operate as endocrine integrator linking metabolism and gonadal function.


Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 268 ◽  
Author(s):  
Izhar Hyder Qazi ◽  
Christiana Angel ◽  
Haoxuan Yang ◽  
Evangelos Zoidis ◽  
Bo Pan ◽  
...  

Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction. In this review, we highlight the implications of selenoproteins in male fertility and reproduction followed by the characteristic biological functions of Se and selenoproteins associated with overall male reproductive function. It is evident from observations of past studies (both animal and human) that Se is essentially required for spermatogenesis and male fertility, presumably because of its vital role in modulation of antioxidant defense mechanisms and other essential biological pathways and redox sensitive transcription factors. However, bearing in mind the evidences from mainstream literature, it is also advisable to perform more studies focusing on the elucidation of additional roles played by the peculiar and canonical selenoproteins i.e., glutathione peroxidase 4 (GPX4) and selenoprotein P (SELENOP) in the male reproductive functions. Nevertheless, search for the elucidation of additional putative mechanisms potentially modulated by other biologically relevant selenoproteins should also be included in the scope of future studies. However, as for the implication of Se in fertility and reproduction in men, though a few clinical trials explore the effects of Se supplementation on male fertility, due to inconsistencies in the recruitment of subjects and heterogeneity of designs, the comparison of such studies is still complicated and less clear. Therefore, further research focused on the roles of Se and selenoproteins is awaited for validating the evidences at hand and outlining any therapeutic schemes intended for improving male fertility. As such, new dimensions could be added to the subject of male fertility and Se supplementation.


Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 143-153 ◽  
Author(s):  
D. Thepot ◽  
J.B. Weitzman ◽  
J. Barra ◽  
D. Segretain ◽  
M.G. Stinnakre ◽  
...  

JunD is one of three mammalian Jun proteins that contribute to the AP-1 transcription factor complex. Distinct regulation and functions have been proposed for each Jun member, but less is known about the biological functions of each of these proteins in vivo. To investigate the role of JunD, we have inactivated the murine gene by replacement with a bacterial lacZ reporter gene. Embryonic JunD expression was initially detected in the developing heart and cardiovascular system. Subsequent broadening phases of JunD expression were observed during embryonic development and expression in the adult was widespread in many tissues and cell lineages. Mutant animals lack JunD mRNA and protein and showed no evidence of upregulation of c-Jun and JunB mRNA levels. In contrast to the other two Jun members, homozygous JunD−/− mutant animals were viable and appeared healthy. However, homozygous JunD−/− animals showed a reduced postnatal growth. Furthermore, JunD−/− males exhibited multiple age-dependent defects in reproduction, hormone imbalance and impaired spermatogenesis with abnormalities in head and flagellum sperm structures. No defects in fertility were observed in JunD−/− female animals. These results provide evidence for redundant functions for members of the Jun family during development and specific functions for JunD in male reproductive function.


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1564 ◽  
Author(s):  
Albert Salas-Huetos ◽  
Emma R. James ◽  
Kenneth I. Aston ◽  
Timothy G. Jenkins ◽  
Douglas T. Carrell ◽  
...  

The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.


2013 ◽  
Vol 110 (09) ◽  
pp. 469-475 ◽  
Author(s):  
Åke Lundwall

SummaryThe human kallikrein locus consists of KLK1, the gene of major tissue kallikrein, and 14 genes of kallikrein-related peptidases (KLKs) located in tandem on chromosome 19q13.3-13.4. In this review, based on information retrieved from the literature or extracted from genome databases, it is hypothesised that the kallikrein locus is unique to mammals. The majority of genes are highly conserved, as demonstrated by the identification of 11 KLK genes in the opossum, a metatherian species. In contrast, a sublocus, encompassing KLK1-4, has gone through major transformations that have generated new genes, which in most cases are closely related to KLK1. In the primate lineage, this process created KLK3, the gene of the prostate cancer marker, prostate-specific antigen (PSA), whereas in the murine lineage it gave rise to 13 genes unique to the mouse and nine unique to the rat. The KLK proteases are effector molecules that emerged early in mammalian evolution and their importance in skin homeostasis and male reproductive function is undisputed and there are also accumulating evidence for a role of KLK proteases in the development of the brain. It is speculated that the KLK gene family arose as part of the process that generated distinguishing mammalian features, like skin with hair and sweat glands, and specialised anatomical attributes of the brain and the reproductive tract.


2005 ◽  
Vol 288 (3) ◽  
pp. C523-C534 ◽  
Author(s):  
Sebastian Brauchi ◽  
Maria C. Rauch ◽  
Ivan E. Alfaro ◽  
Christian Cea ◽  
Ilona I. Concha ◽  
...  

Round spermatid energy metabolism is closely dependent on the presence of l-lactate in the external medium. This l-lactate has been proposed to be supplied by Sertoli cells in the seminiferous tubules. l-Lactate, in conjunction with glucose, modulates intracellular Ca2+ concentration in round spermatids and pachytene spermatocytes. In spite of this central role of l-lactate in spermatogenic cell physiology, the mechanism of l-lactate transport, as well as possible differentiation during spermatogenesis, has not been studied in these cells. By measuring radioactive l-lactate transport and intracellular pH (pHi) changes with pHi fluorescent probes, we show that these cells transport l-lactate using monocarboxylate-H+ transport (MCT) systems. RT-PCR, in situ mRNA hybridization, and immunocyto- and immunohistochemistry data show that pachytene spermatocytes express mainly the MCT1 and MCT4 isoforms of the transporter (intermediate- and low-affinity transporters, respectively), while round spermatids, besides MCT1 and MCT4, also show expression of the MCT2 isoform (high-affinity transporter). These molecular data are consistent with the kinetic data of l-lactate transport in these cells demonstrating at least two transport components for l-lactate. These separate transport components reflect the ability of these cells to switch between the generation of glycolytic l-lactate in the presence of external glucose and the use of l-lactate when this substrate is available in the external environment. The supply of these substrates is regulated by the hormonal control of Sertoli cell glycolytic activity.


2017 ◽  
Vol 29 (9) ◽  
pp. 1803 ◽  
Author(s):  
Caroline S. Martinez ◽  
Franck M. Peçanha ◽  
Daniela S. Brum ◽  
Francielli W. Santos ◽  
Jeferson L. Franco ◽  
...  

Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6 µg kg–1, subsequent doses 0.07 µg kg–1 day–1) resulted in mean (± s.e.m.) blood mercury concentrations of 6.8 ± 0.3 ng mL–1, similar to that found in human blood after occupational exposure or released from removal of amalgam fillings. Even at these low concentrations, mercury was deposited in reproductive organs (testis, epididymis and prostate), impaired sperm membrane integrity, reduced the number of mature spermatozoa and, in the testes, promoted disorganisation, empty spaces and loss of germinal epithelium. Mercury increased levels of reactive oxygen species and the expression of glutathione peroxidase (GPx) 1 and GPx4. These results suggest that the toxic effects of mercury on the male reproductive system are due to its accumulation in reproductive organs and that the glutathione system is its potential target. The data also suggest, for the first time, a possible role of the selenoproteins GPx1 and GPx4 in the reproductive toxicity of mercury chloride.


Author(s):  
Olugbemi T. Olaniyan ◽  
Ayobami Dare ◽  
Gloria E. Okotie ◽  
Charles O. Adetunji ◽  
Babatunde O Ibitoye ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. Evidence shows that SARS-CoV-2 can also affect the urogenital tract. Hence, it should be given serious attention when treating COVID-19-infected male patients of reproductive age group. Other viruses like HIV, mumps, papilloma and Epstein–Barr can induce viral orchitis, germ cell apoptosis, inflammation and germ cell destruction with attending infertility and tumors. The blood-testis barrier (BTB) and blood-epididymis barrier (BEB) are essential physical barricades in the male reproductive tract located between the blood vessel and seminiferous tubules in the testes. Despite the significant role of these barriers in male reproductive function, studies have shown that a wide range of viruses can still penetrate the barriers and induce testicular dysfunctions. Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Martin Blomberg Jensen ◽  
Christine Hjorth Andreassen ◽  
Anne Jørgensen ◽  
John Erik Nielsen ◽  
Li Juel Mortensen ◽  
...  

AbstractInfertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.


2021 ◽  
pp. 1210-1219
Author(s):  
Luiz Eduardo Rodrigues ◽  
Milena Miyoshi Kishibe ◽  
Rogeria Keller ◽  
Heliard Rodrigues dos Santos Caetano ◽  
Marcos Natal Rufino ◽  
...  

Background and Aim: The prebiotics, mannan-oligosaccharides (MOS), demonstrate the ability to increase probiotic microorganisms and fixation and removal of pathogens associated with chronic systemic inflammation in the digestive system. Inflammatory processes play an important role in modulating the brain-intestinal axis, including maintaining male reproductive function and spermatogenesis and regulating stress. The aim of the present study was to evaluate the action of MOS on testosterone and corticosterone concentrations and the reproductive system development of rats in the growth phase as an animal model. Materials and Methods: In total, 128 male rats were used, randomly divided into four experimental groups (n=32): Control; MOS 1; MOS 2; and MOS 3. From each group, eight animals were sacrificed in four experimental moments (14, 28, 42, and 56 days, respectively, moments 1, 2, 3, and 4) and hormonal measurements and histological evaluations were performed. Results: The results revealed the effect of diet, MOS, and timing on testicle weight (p<0.05). At moments 3 and 4, the groups supplemented with MOS showed higher concentrations of testosterone and decreased corticosterone levels throughout the experimental period. Groups supplemented with MOS showed an increase in the frequency of relative sperm and sperm scores. The radii of the seminiferous tubules presented a significant statistical effect of the diet, moments, and diet + moment interaction. Conclusion: It was concluded that the three different MOS prebiotics brought forward sexual maturity.


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