Blood-testis Barrier Research Articles

Prenatal dexamethasone exposure impairs rat blood-testis barrier function and sperm quality in adult offspring via GR/KDM1B/FSTL3/TGFβ signaling.

Both epidemiological and animal studies suggest that adverse environment during pregnancy can change the offspring development programming, but it is difficult to achieve prenatal early warning. In this study we investigated the impact of prenatal dexamethasone exposure (PDE) on sperm quality and function of blood-testis barrier (BTB) in adult offspring and the underlying mechanisms. Pregnant rats were injected with dexamethasone (0.1, 0.2 and 0.4 mg·kg-1·d-1, s.c.) from GD9 to GD20. After weaning (PW4), the pups were fed with lab chow. At PW12 and PW28, the male offspring were euthanized to collect blood and testes samples. We showed that PDE significantly decreased sperm quality (including quantity and motility) in male offspring, which was associated with impaired BTB and decreased CX43/E-cadherin expression in the testis. We demonstrated that PDE induced morphological abnormalities of fetal testicle and Sertoli cell development originated from intrauterine. By tracing to fetal testicular Sertoli cells, we found that PDE dose-dependently increased expression of histone lysine demethylases (KDM1B), decreasing histone 3 lysine 9 dimethylation (H3K9me2) levels of follistatin-like-3 (FSTL3) promoter region and increased FSTL3 expression, and inhibited TGFβ signaling and CX43/E-cadherin expression in offspring before and after birth. These results were validated in TM4 Sertoli cells following dexamethasone treatment. Meanwhile, the H3K9me2 levels of FSTL3 promoter in maternal peripheral blood mononuclear cell (PBMC) and placenta were decreased and its expression increased, which was positively correlated with the changes in offspring testis. Based on analysis of human samples, we found that the H3K9me2 levels of FSTL3 promoter in maternal blood PBMC and placenta were positively correlated with fetal blood testosterone levels after prenatal dexamethasone exposure. We conclude that PDE can reduce sperm quality in adult offspring rats, which is related to the damage of testis BTB via epigenetic modification and change of FSTL3 expression in Sertoli cells. The H3K9me2 levels of the FSTL3 promoter and its expression in the maternal blood PBMC can be used as a prenatal warning marker for fetal testicular dysplasia.

Restoration of fertility in nonablated recipient mice after spermatogonial stem cell transplantation

Spermatogonial stem cell (SSC) transplantation is a valuable tool for studying stem cell-niche interaction. However, the conventional approach requires the removal of endogenous SSCs, causing damage to the niche. Here we introduce WIN18,446, an ALDH1A2 inhibitor, to enhance SSC colonization in nonablated recipients. Pre-transplantation treatment with WIN18,446 induced abnormal claudin protein expression, which comprises the blood-testis barrier and impedes SSC colonization. Consequently, WIN18,446 increased colonization efficiency by 4.6-fold compared with untreated host. WIN18,446-treated testes remained small despite the cessation of WIN18,446, suggesting its irreversible effect. Offspring were born by microinsemination using donor-derived sperm. While WIN18,446 was lethal to busulfan-treated mice, cyclophosphamide- or radiation-treated animals survived after WIN18,446 treatment. Although WIN18,446 is not applicable to humans due to toxicity, similar ALDH1A2 inhibitors may be useful for SSC transplantation into nonablated testes, shedding light on the role of retinoid metabolism on SSC-niche interactions and advancing SSC research in animal models and humans.

Melatonin counteracts cadmium-induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway.

The protective action of melatonin (MLT) against the harmful effects of cadmium (Cd) on testicular activity in rats has been documented previously; however, the involved molecular mechanisms have yet to be elucidated. Herein, we investigate the involvement of the mammalian target of rapamycin (mTOR) on the ability of MLT to counteract the damage induced by Cd on the rat testicular activity. Our study confirmed that Cd has harmful effects on the testes of rats and the protective action exerted by MLT. We reported, for the first time, that the addition of rapamycin (Rapa), a specific mTOR inhibitor, to animals co-treated with Cd and MLT completely abolished the beneficial effects exerted by MLT, indicating that the mTOR pathway partially modulates its helpful effects on Cd testicular toxicity. Interestingly, Rapa-alone treatment, provoking mTOR inhibition, produced altered morphological parameters, increased autophagy of germ and somatic cells, and reduced serum testosterone concentration. In addition, mTOR inhibition also reduced protein levels of markers of steroidogenesis (3β-Hydroxysteroid dehydrogenase) and blood-testis barrier integrity (occludin and connexin 43). Finally, Rapa altered sperm parameters as well as the ability of mature spermatozoa to perform a proper acrosome reaction. Although further investigation is needed to better clarify the molecular pathway involved in MLT action, we confirm that MLT alleviating Cd effects can be used as a supplement to enhance testicular function and improve male gamete quality.

HDAC3 promotes Sertoli cell maturation and maintains the blood-testis barrier dynamics.

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.

Effect of platelet rich plasma versus melatonin on testicular injury induced by Busulfan in adult albino rats: a histological and immunohistochemical study

ABSTRACT This study was done to estimate the testicular histological alterations induced by Busulfan (BUS) and compare the possible protective effects of melatonin (MT) and platelet rich plasma (PRP) in a rat model. Sixty-four male rats were dispersed into: control group, BUS group, melatonin group, and PRP group. Blood samples were processed for biochemical analysis. Tissue specimens were managed for light and electron microscopic studies. Immunohistochemical expression of vimentin and proliferating cell nuclear antigen (PCNA) was performed. Busulfan induced severe testicular damage in all studied methodologies. It showed a statistically significant decrease in serum testosterone and elevation of MDA when compared to the control group. Abnormal testicular cytostructures suggesting defective spermatogenesis were observed: distorted seminiferous tubules, deformed spermatogenic cells, low germinal epithelium height, few mature spermatozoa, and also deformed barrier. Vimentin and PCNA expressions were reduced. Ultrastructurally, Sertoli cells and the blood testis barrier were deformed, spermatogenic cells were affected, and mature spermatozoa were few and showed abnormal structure. Both melatonin and PRP induced improvement in all the previous parameters and restoration of spermatogenesis as confirmed by improvement of Johnsen’s score from 2.6 ± .74 to 7.6 ± .92. In conclusion, melatonin and PRP have equal potential to ameliorate the testicular toxicity of BUS. Melatonin can provide a better noninvasive way to combat BUS induced testicular injury.

Cross-talk between Vimentin and autophagy regulates blood-testis barrier disruption induced by cadmium

The blood-testis barrier (BTB) plays a vital role in mammalian spermatogenesis by separating the seminiferous epithelium into an adluminal and a basal compartment. Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. We observed that Cd can induce BTB disruption, leading to apoptosis of testicular cells. However, the molecular mechanisms contributing to BTB injury induced by Cd have not yet been fully clarified. Vimentin (Vim) is an important desmosome-like junction protein that mediates robust adhesion in the BTB. In this study, we investigated how Vim responds to Cd. We found that Cd treatment led to a significant decrease in Vim expression, accompanied by a marked increase in LC3-II expression and a higer number of autophagosomes. Interestingly, we also observed that Cd-induced autophagy was associated with decreased Vim activity and enhanced apoptosis of testicular cells. To further investigate the role of autophagy in Vim regulation under Cd exposure, we treated cells with an autophagy inhibitor called 3-MA. We found that 3-MA treatment enhanced Vim expression and improved the disruption of the BTB under Cd exposure. Additionally, the inhibition of Vim confirmed the role of autophagy in modulating Vim expression. These results reveal a previously unknown regulatory mechanism of Cd involving the interplay between a heavy metal and a protein.

Threats of nano/microplastics to reproduction and offspring: Potential mechanisms and perspectives

Due to the ubiquitous occurrence in the aquatic environment and terrestrial ecosystem and underlying eco-environmental risks, nano/microplastics (NPs/MPs) have sparked great public concerns. The purpose of this work is aimed to summarize the harmful influence of NPs/MPs on reproduction and offspring health and further explore the potential mechanisms of action, thereby facilitating the more comprehensive understanding of NPs/MPs features. Literature search databases included EMBASE, Web of Science, and PubMed. The study selection and data extraction were implemented according to the inclusion criteria. NPs/MPs could accumulate and trigger reproductive toxic responses and thereafter generate deleterious effects on the offspring health. Accordingly, the reproductive toxicity of NPs/MPs was characterized as the sperm deformity, decline in sperm count and motility, follicular growth tardiness, ovarian fibrosis, granulosa cell death, disorder of reproductive hormone secretion, as well as the fetal growth restriction, glycolipid metabolism disorder, and inflammatory responses of the next generation. Additionally, mechanism research revealed that NPs/MPs exposure brought about inflammatory responses and oxidative stress and thereafter, destroyed the blood-testis barrier (BTB) integrity, motivated spermatogenic cell apoptosis by activating the JNK and p38/MAPK-Nrf2/NF-κB pathways, and induced ovarian granulosa cell pyroptosis and apoptosis and subsequent ovarian fibrosis via the Wnt/β-Catenin and NLRP3/Caspase-1 pathways. Nevertheless, this work also highlighted the imperative requirements for scientific and systematic risk assessments of NPs/MPs, so as to identify the feasible risk mitigation strategies.

Inhibition of miR-143-3p Restores Blood-Testis Barrier Function and Ameliorates Sertoli Cell Senescence.

Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation of miR-143-3p expression. miR-143-3p was found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood-testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulating miR-143-3p. These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Ameliorate Aging-Induced BTB Impairment in Porcine Testes by Activating Autophagy and Inhibiting ROS/NLRP3 Inflammasomes via the AMPK/mTOR Signaling Pathway.

As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos' stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.

Cuproptosis mediates copper-induced testicular spermatogenic cell death.

Cuproptosis, a novel mechanism of programmed cell death, has not been fully explored in the context of spermatogenic cells. This study investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload. Sixty male Institute of Cancer Research (ICR) mice were randomly divided into four groups that received daily oral gavage with sodium chloride (control) or copper sulfate (CuSO 4 ) at 50 mg kg -1 , 100 mg kg -1 , or 200 mg kg -1 , for 42 consecutive days. Mice subjected to copper overload exhibited a disruption in copper homeostasis. Additionally, significant upregulated expression of key cuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis. Immunohistochemical analysis revealed the presence of ferredoxin 1 (Fdx1) in Sertoli cells, Leydig cells, and spermatogenic cells at various stages of testicular development, and the Fdx1-positive staining area was significantly increased in copper-overloaded mice. Mitochondrial dysfunction and decreased adenosine triphosphate levels were also observed, further implicating mitochondrial damage under cuproptosis. Further analyses revealed pathological lesions and blood-testis barrier destruction in the testicular tissue, accompanied by decreased sperm concentration and motility, in copper-overloaded mice. In summary, our results indicate that copper-overloaded mice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death. These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initial experimental evidence for the occurrence of cuproptosis in the testis.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Rreb1 is a key transcription factor in Sertoli cell maturation and function and spermatogenesis in mouse.

Spermatogenesis is a developmental process driven by interactions between germ cells and Sertoli cells. This process depends on appropriate gene expression, which might be regulated by transcription factors. This study focused on Rreb1, a zinc finger transcription factor, and explored its function and molecular mechanisms in spermatogenesis in a mouse model. Our results showed that RREB1 was predominantly expressed in the Sertoli cells of the testis. The decreased expression of RREB1 following injection of siRNA caused impaired Sertoli cell development, which was characterized using a defective blood-testis barrier structure and decreased expression of Sertoli cell functional maturity markers; its essential trigger might be SMAD3 destabilization. The decreased expression of RREB1 in mature Sertoli cells influenced the cell structure and function, which resulted in abnormal spermatogenesis, manifested as oligoasthenoteratozoospermia, and we believe RREB1 plays this role by regulating the transcription of Fshr and Wt1. RREB1 has been reported to activate Fshr transcription, and we demonstrated that the knockdown of Rreb1 caused a reduction in follicle-stimulating hormone receptor (FSHR) in the testis, which could be the cause of the increased sperm malformation. Furthermore, we confirmed that RREB1 directly activates Wt1 promoter activity, and RREB1 downregulation induced the decreased expression of Wt1 and its downstream polarity-associated genes Par6b and E-cadherin, which caused increased germ-cell death and reduced sperm number and motility. In conclusion, RREB1 is a key transcription factor essential for Sertoli cell development and function and is required for normal spermatogenesis.

The Relationship of Gametes and Somatic Cells of Male Gonads of Vertebrates: Evolutionary, Age and Seasonal Aspects, Adaptive and Reactive Transformations Under the Action of Destabilizing Factors

The aim of the study is a comparative analysis of the morphofunctional interactions of germ and somatic cells in the organs of the male reproductive system of vertebrates during ontogenesis, under conditions of changes in reproductive activity and under the influence of destabilizing factors. Material and methods. Using light and electron microscopy, immunohistochemistry and morphometry, the testes of representatives of various classes of vertebrates (amphibians, reptiles, birds and mammals) were studied. The collection of material was carried out in environmentally safe ecosystems and in ecosystems with high anthropogenic load in the Orenburg region of Russia and in the Aktobe region of the Republic of Kazakhstan. Results. Based on the material of our own studies of the gonads, as well as on the basis of information from modern domestic and foreign literature, the patterns of relationships between germ cells and somatic cells of their microenvironment in the testes of vertebrates are shown. The features of the structural organization of the germinal and endocrine components of the male gonads are considered. The features of the structural organization of intertitial endocrinocytes (Leydig cells) are shown, and their high resistance to the action of various destabilizing factors compared to spermatogenic epithelium is established. Pubertal generation of endocrinocytes in vertebrate testes during reproductive age is characterized by stability in cell numbers and belongs to cell populations of a stable type. The role and significance of the structures of the blood-testis barrier are shown and the morphological equivalents of changes in the permeability of this barrier are established; it is revealed that in the studied animals, under the influence of negative anthropogenic factors, the integrity of the blood-testis barrier in the testes is violated. The action of destabilizing factors leads to a decrease in the number of developing germ cells in the lumen of the epididymal tubules (up to their complete disappearance in individual individuals), which is probably due to the deterioration of the trophic influences on them from the structures of the epididymis. Conclusion. The principle of organization of the main compartments of the testes, the convoluted seminiferous tubules and the interstitium of the organ, formed during evolution, probably turned out to be evolutionarily advantageous, since it is represented in the testes of all amniotes - reptiles, birds and mammals. In the process of evolutionary development, several types of structural organization of convoluted seminiferous tubules and interstitium were formed in the testes of vertebrates. The need to protect developing germ cells from the effects of immunocytes, which led to the formation of a blood-testis barrier in the testes.

Hyperuricemia Induces Reproductive Damage in Male Rats through Zinc Homeostasis Imbalance and Oxidative Stress

Studies have reported the adverse effects of hyperuricemia on male reproduction, but the mechanism is still unclear. The purpose of this study is to explore the mechanism of hyperuricemia on reproductive system damage in male rats. The rats were divided into a control group and a model group. Rats were given hypoxanthine and potassium oxonate dissolved in 0.5% (w/v) sodium carboxymethyl cellulose solution to induce the hyperuricemia (HUA) model. After 6 weeks, the blood, testis, and epididymis tissues of the anesthetized rats were collected for further experiments and analysis. Compared with the control rats, the serum uric acid of HUA rats was significantly increased, and the serum testosterone, sperm count, and motility were significantly decreased. The protein expression of testosterone-related molecules CYP11A1, 3β-HSD, and StAR was downregulated in the testis of HUA rats. The protein expression of blood–testis barrier (BTB) related molecules ZO-1 and Connexin43 was downregulated in the testis of HUA rats. Compared with the control group, the zinc content and zinc-containing enzymes (ALP and LDH) were decreased, and the mRNA and protein expression of zinc transporters (ZnT4 and ZIP7) were downregulated in the testis of HUA rats. Furthermore, the level of MDA increased and the activities of CAT, GSH-PX, and SOD decreased in the testicular tissue of HUA rats. The PI3K/AKT/mTOR pathway in the testis of HUA rats was activated. However, there was no significant change in the protein expression of autophagy associated molecules LC3, Beclin1, and ATG5 in the testis of HUA rats. Thus, the conclusion is that hyperuricemia can lead to the destruction of BTB, impaired testosterone synthesis, and decreased sperm count and motility in male rats, mainly by inducing zinc homeostasis imbalance and oxidative stress, rather than autophagy.

Exploring the evolving function of soluble intercellular adhesion molecule-1 in junction dynamics during spermatogenesis.

Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on immune, endothelial, and epithelial cells. Its ectodomain can be proteolytically cleaved to release a circulating soluble form called sICAM-1. Clinical studies demonstrate sICAM-1 is upregulated in various diseases and associated with disease severity. Research has identified sICAM-1 as a regulator of the blood-testis barrier (BTB) and spermatogenesis. Overexpression of sICAM-1 weakened the BTB in vitro and in vivo, downregulated junction proteins including N-cadherin, γ-catenin, and connexin 43, and caused germ cell loss. This contrasts with barrier-strengthening effects of membrane-bound ICAM-1. sICAM-1 may act as a molecular switch enabling germ cells to open BTB and Sertoli-germ cell adhesion for transport across the seminiferous epithelium. While the mechanism remains unclear, reduced SRC family kinase (SFK) signaling was observed following sICAM-1 overexpression. SRC promotes BTB protein endocytosis and degradation, influences cytoskeletal dynamics, and affects cell polarity. As sICAM-1 overexpression phenocopies SRC inhibition, SRC may operate downstream of sICAM-1 in regulating BTB dynamics and spermatogenesis. Investigating sICAM-1's structure-function regions and downstream targets will elucidate the molecular mechanisms of junction disruption. This knowledge could enable strategies targeting sICAM-1/SRC to modulate BTB permeability and treat male infertility or diseases involving endothelial/epithelial barrier dysfunction.

Caveolin 1 Regulates the Tight Junctions between Sertoli Cells and Promotes the Integrity of Blood-Testis Barrier in Yak via the FAK/ERK Signaling Pathway.

Yaks, a valuable livestock species endemic to China's Tibetan plateau, have a low reproductive rate. Cryptorchidism is believed to be one of the leading causes of infertility in male yaks. In this study, we compared the morphology of the normal testis of the yak with that of the cryptorchidism, and found dysplasia of the seminiferous tubules, impaired tightness of the Sertoli cells, and a disruption of the integrity of the blood-testis barrier (BTB) in the cryptorchidism. Previous studies have shown that CAV1 significantly contributes to the regulation of cell tight junctions and spermatogenesis. Therefore, we hypothesize that CAV1 may play a regulatory role in tight junctions and BTB in Yaks Sertoli cells, thereby influencing the development of cryptorchidism. Additional analysis using immunofluorescence, qRT-PCR, and Western blotting confirmed that CAV1 expression is up-regulated in yak cryptorchidism. CAV1 over-expression plasmids and small RNA interference sequences were then transfected in vitro into yak Sertoli cells. It was furthermore found that CAV1 has a positive regulatory effect on tight junctions and BTB integrity, and that this regulatory effect is achieved through the FAK/ERK signaling pathway. Taken together, our findings, the first application of CAV1 to yak cryptorchidism, provide new insights into the molecular mechanisms of cell tight junctions and BTB. This paper suggests that CAV1 could be used as a potential therapeutic target for yak cryptorchidism and may provide insight for future investigations into the occurrence of cryptorchidism, the maintenance of a normal physiological environment for spermatogenesis and male reproductive physiology in the yak.

Comparative Evaluation of Native and Liposomal Curcumin Against Acute Reproductive Toxicity Induced by Cadmium Chloride in Male Mice

Exposure to cadmium chloride (Cd) is linked to reproductive disorders. Curcumin (CUR), a traditional medicinal compound, has been considered for its therapeutic properties. The present study evaluated the antioxidant effects of CUR and liposomal CUR on Cd‐induced testicular toxicity. Mice were exposed to Cd (2.5 mg/kg as a single intraperitoneal dose), Cd + CUR at 50, 100, and 200 mg/kg, and Cd + liposomal CUR (15 mg/kg) orally for 7 days. At the end of the treatment period, histological studies, sperm parameters, oxidative stress parameters, and blood–testis barrier (BTB) integrity were performed. Cd‐induced histopathological deleterious changes in the testis and epididymis tissues increased BTB permeability. It caused a significant decrease in sperm count and viability (p < 0.001), as well as an increase in sperm abnormality (p < 0.001) and a reduction in the antioxidant activity of superoxide dismutase (SOD), glutathione (GSH) (p < 0.001), and increased lipid peroxidation (LPO; p < 0.001) compared to the control group. Co‐treatment of CUR with Cd dose‐dependently and significantly attenuated Cd’s destructive effects on sperm and oxidative stress parameters at 50 mg/kg (p < 0.01) and 100, 200 mg/kg (p < 0.001). Although the liposomal form of CUR showed protective effects against some Cd‐induced changes, such as sperm viability and count (p < 0.001), it did not significantly improve LPO and GSH levels. The results indicated that native CUR prevented Cd‐induced reproductive toxicity in male mice by suppressing oxidative injury, and there was no superior effect of liposomal CUR over native CUR.

Ginsenoside Rg1 improves spermatogenic dysfunction in cryptorchidism model rats by reducing blood-testis barrier damage

Ginsenoside Rg1 improves spermatogenic dysfunction in cryptorchidism model rats by reducing blood-testis barrier damage

Therapeutic Effects of Mesenchymal Stem Cell Conditioned Medium in Rat Varicocele Model.

This study aimed to examine the therapeutic effects of injection of conditioned medium of adipose-derived mesenchymal stem cells (ADMSC-CM) in a surgically created varicocele model in comparison with varicocelectomy. Twenty-eight male Wistar Albino rats were randomly divided into four groups: sham group, varicocele group, varicocelectomy group, and ADMSC-CM injection group. Sperm parameters were analyzed in samples taken from the epididymis after treatment. Malondialdehyde and superoxide dismutase (SOD) levels in blood samples were examined by biochemical analysis. The testicular tissues were stained with hematoxylin-eosin for histological examination (Johnsen's Score). Additionally, Western Blot analyzes were performed to detect Claudin-11 levels, the functional protein of the blood-testis barrier, in testicular tissues. Varicocelectomy and ADMSC-CM treatments significantly improved mean sperm parameters (concentration, progressive motility, motility, normal sperm morphology) (p≤0.05 for all). Both treatment groups had increased SOD levels along with a decrease in malondialdehyde levels (p≤0.05 for all). No significant difference was observed between the ADMSC-CM group and the varicocelectomy group in preserving normal testicular histology according to Johnsen's Score (p=0.114). Levels of Claudin-11 were significantly higher in the varicocelectomy and ADMSC-CM groups compared to the varicocele group (p≤0.05 for all). The therapeutic effects of ADMSC-CM in varicocele model may involve secretion of anti-inflammatory and regenerative factors from ADMSC. ADMSC-CM injection appears to be a promising new strategy in the treatment of varicocele.

АНТИСПЕРМАЛЬНЫЕ АНТИТЕЛА И ПЕРИФЕРИЧЕСКИЙ ДОФАМИН У МУЖЧИН С УЧЕТОМ КОНТРАСТНОЙ ФОТОПЕРИОДИКИ ЕВРОПЕЙСКОГО СЕВЕРА

The physiological role of reference levels of antispermal antibodies (ASABs) in fertile men and mechanisms controlling their concentration are still not fully understood. It is hypothesized that they may contribute to the immunological tolerance of testicles in healthy organism. We investigated the relation between ASABs and dopamine in blood of different groups of males living in the European North with consideration of contrast photoperiodism. Participants were 20 Caucasian males in Arkhangelsk observed over 4 seasonal photoperiods and 108 male dwellers of local settlements (Caucasians, Nenets, komi and metis aborigines), and aborigines migrating nearby who were observed in the periods of minimal light days (December) and then in March. IFA was used to determine concentrations of ASABs in serum and dopamine in blood. Minimal ASABs and increasing dopamine were determined in Archangelsk in the period of maximal daylight hours and in the Caucasian males in settlements in the period of light time which can serve as an argument for specifying periods most favorable for conception. Males in settlements and migrants were distinguished by a higher ASABs level in comparison to the male population in Archangelsk in December against dopamine imbalance due to, probably, oxidative stress and increased permeability of the blood-testis barrier. This finding calls for a close attention to the reproductive system condition. Elevated ASABs levels were observed on the backgrounds of undetectable (0 nmol/l) and abnormal (>0.653 nmol/l) dopamine values, whereas decreased ASABs concentrations were found with dopamine at reference levels. Based on these results of the investigation we assume a dose-dependent dopamine effect on ASABs and propose a hypothesis that control of dopamine in blood could prevent autoimmune sterility.