Dietary restriction-induced alterations on estrogen receptor alpha expression in regulating fertility in male Coturnix coturnix japonica: Relevance of Withania somnifera in modulation of inflammation and oxidative stress in testis.

PROBLEM: Reproductive performance of animals gets affected by nutritional restrictions which act as potential stressors leading to hormonal imbalance and testicular inflammation, the major causes of infertility. Withania somnifera (WS), well-known traditional medicinal plant, has been used as antistress and infertility treatment. Therefore, the present study looks into the ameliorative effects of WS on the reproductive and immune system of male Coturnix coturnix japonica in stressed conditions like water and food restriction focussing on the modulation in estrogen receptor alpha (ERα). METHOD OF STUDY: Biochemical estimations for oxidative stress, histological alterations, immuno-fluorescent localization of ERα, interleukin (IL)-1ß, IL-4, and interferon gamma (IFN-γ) in testicular cells were performed. RESULTS: Nutritional restriction declines endogenous estradiol, ERα in testicular cells while it elevates corticosterone leading to oxidative stress in testis thereby reducing fertility by decrease in sperm. Results indicate significant reversal in all the parameters after the administration of WS by improving testicular cell morphology, increased superoxide and catalase activity thus reducing oxidative stress. WS increases spermatogenesis and enhances expression of ERα in testicular cells in quail. Further, WS increases IL-4, decreases IL-1ß and IFN-γ expression in testis, thereby improving immune profile contrary to stressed conditions. CONCLUSION: WS stimulates HPG-axis even after stress resulting in increased endogenous estradiol which stimulates the expression of ERα in testis; increases sperm count and immunity thereby improving the reproductive performance. WS may be the best therapy against nutritional-restriction stress induced reproductive toxicity by reducing oxidative stress mediated inflammatory response via increased testicular expression of ERα in quail.

CRISPR/Cas9-based genome editing of 14 lipid metabolic genes reveals a sporopollenin metabolon ZmPKSB-ZmTKPR1-1/-2 required for pollen exine formation in maize.

Lipid biosynthesis and transport are essential for plant male reproduction. Compared with Arabidopsis and rice, relatively fewer maize lipid metabolic genic male-sterility (GMS) genes have been identified, and the sporopollenin metabolon in maize anther remains unknown. Here, we identified two maize GMS genes, ZmTKPR1-1 and ZmTKPR1-2, by CRISPR/Cas9 mutagenesis of 14 lipid metabolic genes with anther stage-specific expression patterns. Among them, tkpr1-1/-2 double mutants displayed complete male sterility with delayed tapetum degradation and abortive pollen. ZmTKPR1-1 and ZmTKPR1-2 encode tetraketide α-pyrone reductases and have catalytic activities in reducing tetraketide α-pyrone produced by ZmPKSB (polyketide synthase B). Several conserved catalytic sites (S128/130, Y164/166 and K168/170 in ZmTKPR1-1/-2) are essential for their enzymatic activities. Both ZmTKPR1-1 and ZmTKPR1-2 are directly activated by ZmMYB84, and their encoded proteins are localized in both the endoplasmic reticulum and nuclei. Based on protein structure prediction, molecular docking, site-directed mutagenesis and biochemical assays, the sporopollenin biosynthetic metabolon ZmPKSB-ZmTKPR1-1/-2 was identified to control pollen exine formation in maize anther. Although ZmTKPR1-1/-2 and ZmPKSB formed a protein complex, their mutants showed different, even opposite, defective phenotypes of anther cuticle and pollen exine. Our findings discover new maize GMS genes that can contribute to male-sterility line-assisted maize breeding and also provide new insights into the metabolon-regulated sporopollenin biosynthesis in maize anther.

Arabidopsis pollen-specific glycerophosphodiester phosphodiesterase-like genes are essential for pollen tube tip growth.

In angiosperms, pollen tube growth is critical for double fertilization and seed formation. Many of the factors involved in pollen tube tip growth are unknown. Here, we report the roles of pollen-specific GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE-LIKE (GDPD-LIKE) genes in pollen tube tip growth. Arabidopsis thaliana GDPD-LIKE6 (AtGDPDL6) and AtGDPDL7 were specifically expressed in mature pollen grains and pollen tubes and green fluorescent protein (GFP)-AtGDPDL6 and GFP-AtGDPDL7 fusion proteins were enriched at the plasma membrane at the apex of forming pollen tubes. Atgdpdl6 Atgdpdl7 double mutants displayed severe sterility that was rescued by genetic complementation with AtGDPDL6 or AtGDPDL7. This sterility was associated with defective male gametophytic transmission. Atgdpdl6 Atgdpdl7 pollen tubes burst immediately after initiation of pollen germination in vitro and in vivo, consistent with the thin and fragile walls in their tips. Cellulose deposition was greatly reduced along the mutant pollen tube tip walls, and the localization of pollen-specific CELLULOSE SYNTHASE-LIKE D1 (CSLD1) and CSLD4 was impaired to the apex of mutant pollen tubes. A rice pollen-specific GDPD-LIKE protein also contributed to pollen tube tip growth, suggesting that members of this family have conserved functions in angiosperms. Thus, pollen-specific GDPD-LIKEs mediate pollen tube tip growth, possibly by modulating cellulose deposition in pollen tube walls.

The impact of inflammatory stress on hypothalamic kisspeptin neurons: Mechanisms underlying inflammation-associated infertility in humans and domestic animals.

Inflammatory diseases attenuate reproductive functions in humans and domestic animals. Lipopolysaccharide (LPS), an endotoxin released by bacteria, is known to disrupt female reproductive functions in various inflammatory diseases. LPS administration has been used to elucidate the impact of pathophysiological activation of the immune system on reproduction. Hypothalamic kisspeptin neurons are the master regulators of mammalian reproduction, mediating direct stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) release and consequent release of gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone from the pituitary. The discovery of kisspeptin neurons in the mammalian hypothalamus has drastically advanced our understanding of how inflammatory stress causes reproductive dysfunction in both humans and domestic animals. Inflammation-induced ovarian dysfunction could be caused, at least partly, by aberrant GnRH and LH secretion, which is regulated by kisspeptin signaling. In this review, we focus on the effects of LPS on hypothalamic kisspeptin neurons to outline the impact of inflammatory stress on neuroendocrine regulation of mammalian reproductive systems. First, we summarize the attenuation of female reproduction by LPS during inflammation and the effects of LPS on ovarian and pituitary function. Second, we outline the inhibitory effects of LPS on pulsatile- and surge-mode GnRH/LH release. Third, we discuss the LPS-responsive hypothalamic-pituitary-adrenal axis and hypothalamic neural systems in terms of the cytokine-mediated pathway and the possible direct action of LPS via its hypothalamic receptors. This article describes the impact of LPS on hypothalamic kisspeptin neurons and the possible mechanisms underlying LPS-mediated disruption of LH pulses/surge via kisspeptin neurons.

Rescue of obesity-induced infertility in female mice by silencing AgRP neurons.

Obesity impacts multiple sites of the hypothalamus-pituitary gland-ovary axis (HPO axis) and has become a leading cause of female infertility. However, the critical hypothalamic neurons that participate in the development of obesity-induced infertility have not been well defined yet. Previous studies suggested that metabolic-sensing agouti-related peptide-expressing (AgRP) neurons in the arcuate nucleus (ARC) are hyperactive in diet-induced obesity (DIO) mice. We hypothesize that these neurons may convey metabolic dysfunction onto the HPO axis and contribute to obesity-induced infertility's pathophysiological process. To determine if AgRP neurons in obesity play a necessary role in the development of reproductive impairment in obesity, we used the chemogenetic method to normalize the neuronal activity of AgRP neurons in DIO female mice and test if their fertility can be restored. Our results indicated that chemogenetic inhibition of AgRP neurons could fully rescue the reproductive performance of DIO female mice, as manifested by recovered sex hormonal levels, ovulation, and fecundity. Moreover, we assayed serum AgRP levels in normal-weight and obese women and found elevated AgRP levels in obese subjects, suggesting the correlation between obesity and AgRP neuronal hyperactivity. Our results indicated that AgRP neurons constitute a central node connecting metabolism and reproduction, and dysfunctions of these neurons play a crucial role in reproductive impairment induced by metabolic abnormalities.

SWOLLEN TAPETUM AND STERILITY 1 is required for tapetum degeneration and pollen wall formation in rice.

The pollen wall is important for protecting the male gametophyte and for fertilization. The lipid components of the pollen wall are mainly synthesized and transported from the sporophytic tapetum. Although several factors related to lipid biosynthesis have been characterized, the molecular mechanisms underlying lipid biosynthesis during pollen development in rice (Oryza sativa L.) remain elusive. Here, we showed that mutation in the SWOLLEN TAPETUM AND STERILITY 1 (STS1) gene causes delayed tapetum degradation and aborted pollen wall formation in rice. STS1 encodes an endoplasmic reticulum (ER)-localized protein that contains domain of unknown function (DUF) 726 and exhibits lipase activity. Lipidomic and transcriptomic analyses showed that STS1 is involved in anther lipid homeostasis. Moreover, STS1 interacts with Polyketide Synthase 2 (OsPKS2) and Acyl-CoA Synthetase 12 (OsACOS12), two enzymes crucial in lipidic sporopollenin biosynthesis in pollen wall formation, suggesting a potentially lipidic metabolon for sporopollenin biosynthesis in rice. Collectively, our results indicate that STS1 is an important factor for lipid biosynthesis in reproduction, providing a target for the artificial control of male fertility in hybrid rice breeding and insight into the function of DUF726-containing protein in plants.

TMT-based comparative proteomic analysis of the male-sterile mutant ms01 sheds light on sporopollenin production and pollen development in wucai (Brassica campestris L.).

A spontaneous male-sterile mutant ms01 was discovered from the excellent high-generation inbred line 'hx12-6-3' in wucai. Compared with wild-type 'hx12-6-3', ms01 displayed complete male sterility with degenerated stamens and no pollen. In this study, cytological observation revealed that the tapetum of the anthers of ms01 had degraded in advance, and microspore development had stagnated in the mononuclear stage, ultimately resulting in completely aborted pollen. Genetic analysis indicated that the sterility of ms01 was controlled by a single recessive nuclear gene. In the differential proteomic analysis of 'hx12-6-3' and ms01 flower buds using a tandem mass tags-based approach, a comparison of two stages (stage a and stage e) revealed 1272 differentially abundant proteins (DAPs). The abnormal variation of the anther cuticle, pollen coat, and sporopollenin production were effected by lipid metabolism and phenylpropanoid biosynthesis in the mutant ms01. Further analysis elucidated that pollen development was associated with amino acid metabolism, protein synthesis and degradation, carbohydrate metabolism, flavonoid biosynthesis and glutathione metabolism. These results provide novel insights into the molecular mechanism of GMS (genic male sterility) in wucai. SIGNIFICANCE: ms01, as the first indentified spontaneous male-sterile mutant in wucai, plays a significant role in the initial study of GMS (genic male sterility). In our study, the key DAPs related to anther and pollen development were obtained by TMT-based comparative proteomic analysis. We found that the abnormal accumulation of H2O2 might induce premature degradation of the tapetum, causing anther metabolism disorder and pollen abortion. This process involved multiple DAPs and formed a complex regulatory network that generated a series of physiological metabolic alterations, ultimately leading to male sterility. Our results provide a theoretical foundation for further research on the complex anther and pollen development process.

Neuropeptides as regulators of the hypothalamus-pituitary-gonadal (HPG) axis activity and their putative roles in stress-induced fertility disorders.

Neuropeptides being regulators of the hypothalamus-pituitary-adrenal (HPA) axis activity, also affect the function of the hypothalamus-pituitary-gonadal (HPG) axis by regulating gonadotrophin-releasing hormone (GnRH) secretion from hypothalamic neurons. Here, we review the available data on how neuropeptides affect HPG axis activity directly or indirectly via their influence on the HPA axis. The putative role of neuropeptides in stress-induced infertility, such as polycystic ovary syndrome, is also described. This review discusses both well-known neuropeptides (i.e., kisspeptin, Kp; oxytocin, OT; arginine-vasopressin, AVP) and more recently discovered peptides (i.e., relaxin-3, RLN-3; nesfatin-1, NEFA; phoenixin, PNX; spexin, SPX). For the first time, we present an up-to-date review of all published data regarding interactions between the aforementioned neuropeptide systems. The reviewed literature suggest new pathophysiological mechanisms leading to fertility disturbances that are induced by stress.

Efficacy of N-acetyl- l-cysteine against glyphosate induced oxidative stress and apoptosis in testicular germ cells preventing infertility.

The present era's demand for continuous pesticides' use to increase the agriculture outcome, has caused numerous health effects among which mammalian infertility, owing to reproductive toxicity, is serious. Thus, the present study emphasizes upon glyphosate (GLY) induced toxicity and mitigating effects of N-acetyl cysteine (NAC) in testicular cells of caprine by using various cytotoxic and biochemical parameters. GLY was found to induce several apoptotic attributes such as pyknotic nuclei, tubular degeneration, increased vacuolization, and so on, in testicular cells. GLY also decreased the cell viability and increased the incidence of apoptosis in testicular cells in a dose- and time-dependent manner as revealed by MTT assay and Fluorescence (ethidium bromide/acridine orange) assay, respectively. It also increased the level of oxidative stress as evident with an increase in lipid peroxidation and decline in antioxidant power along with the decreased enzymatic activity of different antioxidant enzymes (SOD, CAT, and GST). However, NAC supplementation showed antagonistic results in GLY-treated testicular tissues with maximum amelioration at the highest dose, thereby decreasing GLY-mediated apoptosis rate and oxidative stress. Maximum amelioration was reported at 10 mM NAC concentration. Reduced GLY toxicity due to NAC will prove NAC to be an excellent approach for dealing with male reproductive toxicity at the cellular level, benefiting the mammalian reproductive status.

The effect of oral melatonin supplementation on MT-ATP6 gene expression and IVF outcomes in Iranian infertile couples: a nonrandomized controlled trial.

This study aims to evaluate the effect of melatonin supplementation on the outcomes of in vitro fertilization (IVF) and mitochondrial adenosine triphosphate production (MT-ATP6) gene expression in Iranian infertile couples. A single-blind nonrandomized controlled trial was conducted, recruiting 90 infertile couples who underwent IVF at an infertility center in Tehran, Iran. Patients who were assigned to the intervention group received melatonin as a supplementation to the standard controlled ovarian stimulation (COS). The control group received a COS protocol only. Primary outcome was the mRNA level of the MT-ATP6 gene in cumulus cells of ovarian follicles. Secondary outcomes were the mean number of mature oocytes retrieved, the embryo quality, and biochemical and clinical pregnancy rates. The mRNA level of the MT-ATP6 gene in cumulus cells between intervention and control groups was not statistically different (0.931 vs.1; P Ëƒ 0.05). The mean number of poor-quality embryos was significantly lower in the intervention group than that in the control group (0.27 vs. 0.80; P = 0.028). The biochemical and clinical pregnancy rates were higher in the intervention group (24% vs. 14%, P = 0.089, and 14% vs. 7%, P = 0.302, respectively); however, the difference was not significant. Melatonin supplementation did not increase the odds of clinical pregnancy and the number of mature oocytes retrieved, but significantly reduced the number of low-quality embryos. More extensive studies focusing on the level of MT-ATP6 gene expression in the oocyte or blastomere cells may further elucidate the effect of supplementation with melatonin in infertile couples who have poor clinical outcomes. Trial registration: Current Controlled Trials: IRCT2015042912307N4.

Calcium Supplementation Alleviates High-Fat Diet-Induced Estrous Cycle Irregularity and Subfertility Associated with Concomitantly Enhanced Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue.

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.

Walnut leaf extract acts as a fertility agent in male Wistar albino rats - A search for herbal male fertility enhancer.

Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0.9%) saline only; Groups II, III, IV received 50, 500, 1,000 mg/kg body weight (BW) of T. conophorum leaf extract orally, while Group V served as standard and was given suspension of clomiphene citrate orally at the dose of 1.04 mg/kg/ml BW. The extract and drug were given daily and the experiment lasted for 21 consecutive days. Results The testicular biochemical parameters in treated groups showed significant (p<0.05) increase in lactate dehydrogenase activity activity, Glucose-6-phosphate dehydrogenase (G-6PDH) activity, glycogen content, 3ß and 17ß hydroxysteroid dehydrogenase activities and testicular and epididymal Zn and Se contents with a significant decrease in cholesterol content. A significant increase in testis weight and epididymis weight were also observed. Also, a significant (p<0.05) increase in the level of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone, sperm count, motility, viability and a decrease in sperm abnormality were observed in the various treated groups when compared with the control group. This increment was concentration dependent, while the extract at the highest concentration showed a more pronounced effect than the standard drug. Also, no sperm DNA fragmentation index was found in all the treatment groups. Photomicrographs from light and scanning electron microscopy showed large fenestrae of interstitial tissue, large fluid space and intact seminiferous epithelium layers fully packed with spermatogenic cells in treated groups than the control group. Conclusions The present study has demonstrated that Tetracarpidium conophorum leaf possesses fertility-enhancing property and have useful effects on spermatogenesis and sperm parameters in rats.

Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates mammalian fertility. Herein we demonstrate a critical role for the homeodomain transcription factor ventral anterior homeobox 1 (VAX1) in GnRH neuron maturation and show that Vax1 deletion from GnRH neurons leads to complete infertility in males and females. Specifically, global Vax1 knock-out embryos had normal numbers of GnRH neurons at 13 d of gestation, but no GnRH staining was detected by embryonic day 17. To identify the role of VAX1 specifically in GnRH neuron development,Vax1(flox)mice were generated and lineage tracing performed in Vax1(flox/flox):GnRH(cre):RosaLacZ mice. This identified VAX1 as essential for maintaining expression of Gnrh1 The absence of GnRH staining in adult Vax1(flox/flox):GnRH(cre)mice led to delayed puberty, hypogonadism, and infertility. To address the mechanism by which VAX1 maintains Gnrh1 transcription, the capacity of VAX1 to regulate Gnrh1 transcription was evaluated in the GnRH cell lines GN11 and GT1-7. As determined by luciferase and electrophoretic mobility shift assays, we found VAX1 to be a direct activator of the GnRH promoter through binding to four ATTA sites in the GnRH enhancer (E1) and proximal promoter (P), and able to compete with the homeoprotein SIX6 for occupation of the identified ATTA sites in the GnRH promoter. We conclude that VAX1 is expressed in GnRH neurons where it is required for GnRH neuron expression of GnRH and maintenance of fertility in mice. SIGNIFICANCE STATEMENT: Infertility classified as idiopathic hypogonadotropic hypogonadism (IHH) is characterized by delayed or absent sexual maturation and low sex steroid levels due to alterations in neuroendocrine control of the hypothalamic-pituitary-gonadal axis. The incidence of IHH is 1-10 cases per 100,000 births. Although extensive efforts have been invested in identifying genes giving rise to IHH, >50% of cases have unknown genetic origins. We recently showed that haploinsufficiency of ventral anterior homeobox 1 (Vax1) leads to subfertility, making it a candidate in polygenic IHH. In this study, we investigate the mechanism by which VAX1 controls fertility finding that VAX1 is required for maintenance of Gnrh1 gene expression and deletion of Vax1 from GnRH neurons leads to complete infertility.

[Efficacy of Chinese Herbs in Multiple Paths for Tubal Factor Infertility Patients and Their Effects on Serum Inflammatory Factors].

Objective To evaluate the clinical efficacy of Chinese herbs in multiple paths for tub- al factor infertility (TFI) patients, and to observe their effects on serum inflammatory factor. Methods Totally 100 TFl patients were assigned to the observation group and the control group according to grouping sequence, 50 in each group. All patients received laparoscopy. Patients in the observation group were additionally combined with traditional Chinese herbal treatment program in multiple paths (oral administration of Chinese herbs + retention enema of Chinese herbs + iontophoresis). All treatment lasted for 3 successive months. Scores of Chinese medicine (CM) symptoms, clinical efficacy, pregnancy rate, and levels of interleukin-6 ( IL-6) and tumor necrosis factor-α ( TNF-α) were compared between the two groups after 6 months of treatment. Results Scores of CM symptoms were significantly lower in the two groups after treatment ( P <0. 05). They were lower in the observation group than in the control group (P <0. 05). Serum levels of TNF-a and IL-6 were significantly lower in the observation group than in the control group, with statistical difference (P <0. 05). The effective rate was 96. 0% (48/50) in the observation group and 82. 0% (41/50) in the control group, with statistical difference (x² =5. 005, P <0. 05). After one year of postoperative follow-up, the intrauterine pregnancy rate was 58. 0% (29/50) in the observation group and 34. 0% (17/50) in the control group, with statistical difference (x² =5.797, P <0. 05). The ectopic gestation occurred in one patient of the control group, and none in the observation group, with no statistical difference in the ectopic gestation rate between the two groups (x² =1. 010, P >0. 05). Conclusion Chinese herbs in multiple paths for treating TFI could significantly improve clinical symptoms, reduce expressions of serum inflammatory factors, and elevate efficacy and pregnancy rate, which showed superiority when compared with laparoscopy alone.

Potential Clinical Use of Kisspeptin.

Over the last 10 years, kisspeptins--peptide products of varying lengths encoded by the KISS1 gene--have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they elicit an effect on the central gonadotropin-releasing hormone neurons. Administration of kisspeptin by either the subcutaneous or intravenous route potently stimulates endogenous gonadotropin hormone release in healthy men and women as well as in animals. Kisspeptin also stimulates endogenous release of gonadotropins in subfertile as well as healthy volunteers, and therefore it has potential as a novel therapeutic agent in reproductive disorders. Further human studies have shown that chronic, high-dose administration of kisspeptin causes desensitisation with rapid subsequent suppression of the hypothalamic-pituitary-gonadal axis, and therefore high-dose long-acting analogues may have a clinical role in treating sex hormone-dependent malignancies. By further elucidating the intricacies and mechanisms of the kisspeptin signalling system, and the tissues it acts on during different phases of the reproductive timeline (including during puberty, fertility, pregnancy and menopause), pharmacologic analogues could become clinically useful.

Melatonin: shedding light on infertility?--A review of the recent literature.

In recent years, the negative impact of oxidative stress on fertility has become widely recognised. Several studies have demonstrated its negative effect on the number and quality of retrieved oocytes and embryos following in-vitro fertilisation (IVF). Melatonin, a pineal hormone that regulates circadian rhythms, has also been shown to exhibit unique oxygen scavenging abilities. Some studies have suggested a role for melatonin in gamete biology. Clinical studies also suggest that melatonin supplementation in IVF may lead to better pregnancy rates. Here we present a critical review and summary of the current literature and provide suggestions for future well designed clinical trials.

[Effect of Yijing Recipe on apoptosis of testis spermatogenic cells and the expression of Bcl-2 and Bax protein in infertility rats].

OBJECTIVE: To observe the effect of Yijing Recipe (YR) on the apoptosis of testis spermatogenic cells and the protein expression of Bcl-2/Bax in rats with adenine induced infertility. METHODS: Totally 75 Wistar rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the high dose YR group, the middle dose YR group, and the low dose YR group, 15 in each group. Except those in the blank control group, rats in the rest groups were intragastrically administered with adenine for 10 successive days. From the 11th day, rats in the blank control group and the model group were fed with equal volume of normal saline. Rats in the YR groups were intragastrically administered with YR at different doses (3.38 g/100 g; 1.69 g/100 g; 0.85 g/100 g), once daily for 20 consecutive days. All rats were killed by the end of the experiment and their testes extracted. The apoptosis of spermatogenic cells and the expression of Bcl-2/Bax proteins were detected by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) and SABC method. RESULTS: Compared with the blank control group, the Bcl-2 protein expression decreased, the Bax protein expression increased, and the apoptosis index increased in the model group, showing statistical difference (P <0.01). Compared with the model group, the Bcl-2 protein expression increased in the three YR treated groups (P <0.01, P <0.05). The Bax protein expression level decreased in the high and middle dose YR groups (P <0. 01, P <0. 05). The apoptosis index decreased in the middle dose YR group (P <0.01). CONCLUSION: YR could inhibit the apoptosis of spermatogenic cells through regulating the expression of Bcl-2 and Bax protein in the testis.

Disrupted kisspeptin signaling in GnRH neurons leads to hypogonadotrophic hypogonadism.

Landmark studies have shown that mutations in kisspeptin and the kisspeptin receptor (Kiss1r) result in reproductive dysfunction in humans and genetically altered mouse models. However, because kisspeptin and its receptor are present in target cells of the central and peripheral reproductive axis, the precise location(s) for the pathogenic signal is unknown. The study described herein shows that the kisspeptin-Kiss1r signaling pathway in the GnRH neuron is singularly critical for both the onset of puberty as well as the attainment of normal reproductive function. In this study, we directly test the hypothesis that kisspeptin neurons regulate GnRH secretion through the activation of Kiss1r on the plasma membrane of GnRH neurons. A GnRH neuron-specific Kiss1r knockout mouse model (GKirKO) was generated, and reproductive development and phenotype were assessed. Both female and male GKirKO mice were infertile, having low serum LH and FSH levels. External abnormalities such as microphallus and decreased anogenital distance associated with failure of preputial gland separation were present in GKirKO males. A delay in pubertal onset and abnormal estrous cyclicity were observed in female GKirKO mice. Taken together, these data provide in vivo evidence that Kiss1r in GnRH neurons is critical for reproductive development and fertility.

[The role of selenium in endocrine system diseases]. / A szelén szerepe az endokrin betegségekben.

Oxygen derived free radicals, generated by a number of cellular reactions, include superoxide anion, hydrogen peroxide and hydroxyl radicals. They exert their cytotoxic effects mainly via peroxidation of the cell membrane resulting in the loss of membrane integrity. The essential trace element, selenium exerts complex effects on the endocrine systems, partly due to its antioxidant capacity. Well-characterized selenoproteins include iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases involved in thyroid hormone metabolism and protection from oxidative damage. The value of selenium supplementation in autoimmune thyroid disorders has been investigated and most studies confirmed the beneficial effect of selenium supplementation in Hashimoto's and Graves's diseases. Recently, selenium proved to be effective in mild inflammatory orbitopathy. There are a number of reports about the effect of selenium in diabetes mellitus, but the data are controversial as both insulin-like and diabetes-inducing effects of selenium have been described. Selenium was successfully used in both female and male infertility of autoimmune origin.