Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

Gene co-expression networks contributing to reproductive development in Holstein-Friesian bull calves.

Enhanced early life nutrition stimulates the functionality of the hypothalamic-pituitary-testicular (HPT) biochemical signalling axis, resulting in precocious reproductive development in bull calves. Additionally, there is evidence that peptides and hormones produced within adipose tissue depots are also central in mediating the effect of metabolic status with reproductive development. The objective of this study was to undertake gene co-expression analyses on transcriptional data of the HPT and adipose tissues derived from bull calves fed contrasting planes of nutrition up to 18 weeks of life. The relationship between networks of co-expressed genes in each tissue dataset with calf phenotypic data was also assessed using a Pearson correlation analysis. Phenotypic data were related to metabolic status (systemic concentrations of insulin, leptin, adiponectin and IGF-1) reproductive development (systemic concentrations of testosterone, FSH and LH) and markers of testicular development (seminiferous tubule diameter, seminiferous tubule lumen score, spermatogenic cells and Sertoli cells). In the hypothalamus, gene co-expression networks involved in biochemical signalling processes related to gonadotropin-releasing hormone (GnRH) secretion were positively associated (P < 0.05) with systemic concentrations of IGF-1 and insulin. Similarly, a network of gene transcripts involved in GnRH signalling in the anterior pituitary was positively associated (P < 0.05) with systemic concentrations of LH. In the testes and adipose tissues, networks of co-expressed genes implicated in cholesterol and fatty acid biosynthesis were positively associated (P < 0.05) with lumen score, Sertoli cell number, and stage of spermatogenesis. Additionally, gene co-expression networks significantly associated (P < 0.05) with both metabolic and reproductive trait data were found to be enriched (P < 0.05) for biological pathways related to energy production, cellular growth and proliferation, GnRH signalling and cholesterol biosynthesis across multiple tissues examined. Results from this study highlight networks of co-expressed genes directly associated with markers of enhanced metabolic status and subsequent earlier reproductive development. Furthermore, genes involved in biological processes mentioned above may hold potential for informing genomic selection breeding programmes for the selection of calves capable of displaying earlier reproductive development as a consequence of enhanced dietary intake.

Biogenic zinc-oxide nanoparticles of Moringa oleifera leaves abrogates rotenone induced neuroendocrine toxicity by regulation of oxidative stress and acetylcholinesterase activity.

Zinc oxide nanoparticles (ZnONPs) from plant origin were postulated to regulate complex hormonal control through the hypothalamus- pituitary-testicular axis and somatic cells due to their unique small size and effective drug delivery to target tissues. This study therefore investigates the biogenic synthesis of zinc oxide nanoparticles (ZnO NPs) from Moringa oleifera leaves on key endocrine hormones (LH, FSH and testosterone), MDA level, antioxidant enzymes (SOD and CAT), acetylcholineesterase (AChE) activity and reactive nitrogen species (NO•) level in rotenone induced male rat. The animals were divided into six groups (n = 8). Group I was orally given olive oil as vehicle; Group II received 60 mg/kg of rotenone (RTNE) only; Group III (RTNE + ZnONPs) received 60 mg/kg RTNE + 10 mg/kg ZnONPs; Group IV (RTNE + ZnCAP) received 60 mg/kg RTNE + 50 mg/kg zinc capsule; Group V (ZnONPs only) received 10 mg/kg ZnONPs only. Group VI received 50 mg/kg ZnCAP only. The experiment lasted 10 days. TEM and XRD images revealed ZnO NPs. Moreover, the presence of organic molecules in bio-reduction reactions from the FTIR spectrum showed the stabilization of the nanoparticles. Also, animals induced with rotenone exhibited impairment in the leydig cells by depleting LH, FSH, and testosterone levels with reduced AChE activity and significant (p < 0.05) alteration in cerebral enzymatic antioxidants. There was also brain increase in NO• production: marker of pro-inflammation. Nanotherapeutically, ZnONPs regulated hypothalamus-pituitary-testicular axis via modulation of cerebral NO•, FSH, LH, testosterone and AChE activity with induction of anti-oxidative enzymes.

Molecular clues in the regulation of mini-puberty involve neuronal DNA binding transcription factor NHLH2.

Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini-puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. However, the expression of these genes in prepubertal gonads has not been studied systematically, and little is known about the effect of hormone therapy on their testicular and neuronal expression levels. In this review, we interpret histological sections, data on hormone levels, and RNA profiling data from adult normal testes compared to pre-pubertal low infertility risk (LIR) and high infertility risk (HIR) patients randomly treated with surgery in combination with GnRHa or only surgery. We organize 31 target genes relevant for idiopathic hypogonadotropic hypogonadism and cryptorchidism into five classes depending on their expression levels in HIR versus LIR samples and their response to GnRHa treatment. Nescient-helix-loop-helix 2 (NHLH2) was the only gene showing a decreased mRNA level in HIR patients and an increase after GnRHa treatment. This phenomenon may reflect a broader effect of hormone treatment on gene expression in both testicular and central nervous system tissues, which could explain why the hypothalamus-pituitary-testicular axis is permanently restored by the administration of GnRHa.

RéSUMé: Le traitement par l'agoniste de l'hormone de libération des gonadotrophines (GnRHa) suite à une intervention chirurgicale pour cryptorchidie rétablit la mini-puberté par des effets endocrinologiques et transcriptionnels et prévient l'infertilité adulte dans la plupart des cas. Plusieurs gènes jouent un rôle important dans l'hypogonadisme hypogonadotrope central chez les mammifères, dont certains sont transcrits à la fois dans le cerveau et les testicules. Cependant, l'expression de ces gènes dans les gonades prépubères n'a pas été étudiée systématiquement et l'effet de l'hormonothérapie sur leurs niveaux d'expression testiculaire et neuronale n'est pas connu. Dans cette revue, nous interprétons des coupes histologiques, des données sur les taux d'hormones et des données de profilage d'ARN provenant de testicules normaux adultes et des patients prépubères à faible risque d'infertilité (LIR) et à haut risque d'infertilité (HIR) traités par chirurgie en association avec la GnRHa ou seulement la chirurgie dans le cadre d'une étude randomisée. Nous organisons 31 gènes cibles pertinents pour l'hypogonadisme hypogonadotrope idiopathique et la cryptorchidie en cinq classes en fonction de leurs niveaux d'expression dans les échantillons HIR et LIR et de leur réponse au traitement par GnRHa. Nescient-helix-loop-helix 2 (NHLH2) était l'unique gène dont le niveau d'ARNm diminue chez les patients HIR par rapport aux LIR et augmente suite au traitement par GnRHa. Ce phénomène pourrait être révélateur d'un effet généralisé du traitement hormonal sur l'expression des gènes dans les tissus testiculaires et du système nerveux central. Cela pourrait expliquer pourquoi l'axe hypothalamo-hypophyso-gonadique est définitivement rétablie par l'administration de la GnRHa.

Role of AURKA in the hypothalamus-pituitary-testicular axis in Tibetan sheep from Tianzhu.

The mitosis-associated protein aurora kinase A (AURKA) regulates the maturation of germ cells. We have previously reported using transcriptome analysis that AURKA is expressed in yak testes. Although Tibetan sheep possess an immense economic value, their reproductive rate is low. Herein, the expression and functions of AURKA in the hypothalamus-pituitary-testicular (HPT) axis in Tibetan sheep from Tianzhu were investigated. The cDNA sequence of sheep AURKA was cloned and bioinformatics techniques were used to predict its structure. Tissue expression of AURKA was determined by qPCR, immunoblotting, immunostaining, and immunohistochemistry. The AURKA coding sequence was found to be 1218 bp in length, encoding a 405-amino acid polypeptide chain. Furthermore, the highest sequence similarity of AURKA with the corresponding sequence in other species was seen in goat and cattle; the least degree of similarity was seen in the domestic cat. In addition, AURKA expression was elevated in the testes compared to that in the hypothalamus and pituitary (p < 0.01). Moreover, AURKA was mainly localized in the hypothalamic paraventricular nucleus (magnocellular), chromophobe cells of the pituitary, and spermatogenic cells of the testis. These results indicated that AURKA might participate in sheep reproductive regulation, thus providing a reference for the study of AURKA function in the reproductive process of Tibetan sheep from Tianzhu.

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring.

One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother's treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus-pituitary-testicular axis regulation in F1 offspring.

Fluoride exposure changed the structure and the expressions of reproductive related genes in the hypothalamus-pituitary-testicular axis of male mice.

Numerous studies have shown that fluoride exposure adversely affected the male reproductive function, while the molecular mechanism is not clear. The present study was to investigate the effects of fluoride exposure (60 days) on the expressions of reproductive related genes, serum sex hormone levels and structures of the hypothalamus-pituitary-testicular axis (HPTA), which plays a vital role in regulating the spermatogenesis in male mice. In this study, 48 male mice were administrated with 0, 25, 50, and 100 mg/L NaF through drinking water. Results showed that the malformation ratio of sperm was significantly increased (P<0.05). At transcriptional level, the expression levels of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), inhibin alpha (INHα), inhibin beta-B (INHßB), and sex hormone binding globulin (SHBG) mRNA in testis were significantly decreased (P<0.05). Moreover, histological lesions in testis and ultrastructural alterations in hypothalamus, pituitary and testis were obvious. However, the same fluoride exposure did not lead to significant changes of related mRNA expressions in hypothalamus and pituitary (P>0.05). Also, there were no marked changes in serum hormones. Taken together, we conclude that the mechanism of HPTA dysfunction is mainly elucidated through affecting testes, and its effect on hypothalamus and pituitary was secondary at exposure for 60 days.

Short QTc interval in males with klinefelter syndrome-influence of CAG repeat length, body composition, and testosterone replacement therapy.

BACKGROUND: Klinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. OBJECTIVE: To investigate ECGs in males with KS and compare with controls. METHODS: Case control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1%). The QT-interval was measured using "teach-the-tangent" method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc < 330 ms. RESULTS: Compared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found. CONCLUSION: We found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.