Developmental health risks of chronical exposure to low doses of foodborne persistent organic pollutants (POP) are recognized but still largely uncharacterized. Juvenile female BALB/c mice exposed to either HBCD, CB-153 or TCDD at doses relevant to human dietary exposures (49.5 μg, 1.35 μg and 0.90 pg kg-1 bw-1 day-1, respectively) for 28 days displayed histopathological changes in liver (HBCD, CB-153, TCDD), thymus (HBCD, CB-153) and uterus (HBCD), reduced serum oestradiol 17β (E2) levels (HBCD), increased serum testosterone (T) levels (CB-153) and an increased T/E2 ratio (HBCD). Proteomics analysis of brain provided molecular support for the HBCD-induced reduction in E2. Neural gene expression analysis, confirmed effects on 18 out of 30 genes previously found to affected after exposure to higher doses to the same pollutants. Our findings indicate that exposure to POP at low doses is associated with subtle, but toxicological relevant effects on post-natal development in female mice.

Territorial aggression has been widely studied in males and it has been historically suggested that androgens are key mediators of this behavior. However, more recent evidence suggests that it is the aromatization to estrogens, rather than androgens themselves, that is key to regulating this behavior. Females also display aggressive behaviors, but the physiological regulation of female aggression is still understudied when compared to males. In this context, the challenge hypothesis postulates that male-male aggressive interactions stimulate the production of androgens in males in periods of social instability. Here we determine plasma sex steroid levels in Cichlasoma dimerus to assess whether estrogens are related to aggressive behavior and to test the challenge hypothesis in both males and females. We set-up challenge trials as intrasexual dyadic encounters and determined androgen and estrogen levels before and after the trial in both winners and losers. Even though there were no differences in initial estradiol-17β plasma levels between male winners and losers, initial levels were higher (p = .046) in female winners than in losers, while there were no differences in testosterone or 11-ketotestosterone levels. After trials, both males and females showed elevated levels of estradiol-17β and both androgens, but only males exhibited a significant 1.45, 5.42 and 3.2-fold increase in estradiol-17β, testosterone and 11-ketotestosterone, respectively (p = .023, p = .016, p = .018). Moreover, changes in circulating levels of estradiol-17β in females after the trials do not depend on their reproductive status or on the outcome of the contest. We suggest that female aggression is associated with initial levels of estradiol-17β, and that the challenge hypothesis, originally defined for androgens, could also be extended to estrogens.

A few decades ago, cardiac muscle was discovered to possess signalling pathways that, when activated, protect the myocardium against the damage induced by ischaemia-reperfusion. The ability of cardiac muscle to protect itself against injury has been termed 'cardioprotection'. Many compounds and procedures can trigger cardioprotection including conditionings (exposure to brief episodes of ischaemia-reperfusion to protect against sustained ischaemia-reperfusion), hypoxia, adenosine, acetylcholine, adrenomedullin, angiotensin, bradykinin, catecholamines, endothelin, estrogens, phenylephrine, opioids, testosterone, and many more. These triggers activate many intracellular signalling factors including protein kinases, different enzymes, transcription factors and defined signalling pathways to target structures in mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma to mediate cardioprotection. Although a lot of information about cardioprotection has been acquired, there are still two major outstanding issues to be addressed in the future 1) better understanding of spatio-temporal relationships between signalling elements, and; 2) devising therapeutic strategies against myocardial diseases based on cardioprotective signalling. Further research is required to paint integral picture of cardioprotective signalling and more clinical studies are required to properly test clinical efficacy and safety of potential cardioprotective strategies. Therapies against cardiac diseases based on cardioprotective strategies would be a perfect adjunct to current therapeutic strategies based on restitution of coronary blood flow and regulation of myocardial metabolic demands.

Learned vocalization, including birdsong and human speech, is acquired through self-motivated vocal practice during the sensitive period of vocal learning. The zebra finch (Taeniopygia guttata) develops a song characterized by vocal variability and crystalizes a defined song pattern as adulthood. However, it remains unknown how vocal variability is regulated with diurnal singing during the sensorimotor learning period. Here, we investigated the expression of activity-dependent neuroplasticity-related gene Arc during the early plastic song phase to examine its potential association with vocal plasticity. We first confirmed that multiple acoustic features of syllables in the plastic song were dramatically and simultaneously modulated during the first 3 hours of singing in a day and the altered features were maintained until sleep. Concurrently, Arc was intensely induced during morning singing and a subsequent attenuation during afternoon singing in the robust nucleus of the arcopallium (RA) and the interfacial nucleus of the nidopallium (NIf). The singing-driven Arc expression was not altered by circadian rhythm, but rather reduced during the day as juveniles produced more songs. Song stabilization accelerated by testosterone administration in juveniles was accompanied with attenuation of Arc induction in RA and NIf. In contrast, although early-deafened birds produced highly unstable song even at adulthood, singing-driven Arc expression was not different between intact and early-deafened adults. These results suggest a potential functional link between Arc expression in RA and NIf and vocal plasticity during the sensorimotor phase of song learning. Nonetheless, Arc expression did not reflect the quality of bird's own song or auditory feedback. This article is protected by copyright. All rights reserved.

One-third of men with obesity or type 2 diabetes have subnormal free testosterone concentrations. The lower free testosterone concentrations are observed in obese men at all ages, including adolescents at completion of puberty. The gonadotropin concentrations in these males are inappropriately normal; thus, these patients have hypogonadotropic hypogonadism (HH). The causative mechanism of diabesity-induced HH is yet to be defined but is likely multifactorial. Decreased insulin and leptin signaling in the central nervous system are probably significant contributors. Contrary to popular belief, estrogen concentrations are lower in men with HH. Men with diabesity and HH have more fat mass and are more insulin resistant than eugonadal men. In addition, they have a high prevalence of anemia and higher mortality rates than eugonadal men. Testosterone replacement therapy results in a loss of fat mass, gain in lean mass, and increase in insulin sensitivity in men with diabesity and HH. This is accompanied by an increase in insulin-signaling genes in adipose tissue and a reduction in inflammatory mediators that interfere with insulin signaling. There is also an improvement in sexual symptoms, anemia, LDL cholesterol, and lipoprotein (a). However, testosterone therapy does not consistently affect HbA1c in men with diabetes. The effect of testosterone replacement on cardiovascular events or mortality in men with diabesity is not known and remains to be studied in prospective trials.

The aim of the study was to determine the time after treatment with a 4.7 mg deslorelin implant until Tomcat spermatogenesis activity was restored, and seminal parameters reached pre-implant values. Tomcats (n = 6) were randomly assigned to one of two treatments. Three cats (n = 3) received a deslorelin implant (4.7 mG; Suprelorin®, Virbac, France) in the interscapular subcutaneous region whereas three (n = 3) received no implant and served as control group. Semen samples were collected by electroejaculation every 4 wk from 3 mo before treatment (pretreatment samples) until reestablishment of pre-treatment sperm quality, 32 mo post-implant insertion (PI). Each semen sample was assessed for motility, velocity, concentration, total sperm count, viability, acrosome integrity, plasma membrane integrity and sperm morphology. After semen collection, testicular volume and presence/absence of penile spines were recorded. Additionally, blood samples were taken to measure testosterone concentration. An increase in sperm concentration and total sperm count was present 1 mo PI despite of an abrupt decrease in serum testosterone concentrations after 2-4 weeks. This initial stimulatory effect was followed by a decrease in seminal parameters, reduction of testicular volume and disappearance of penile spines 2 mo PI. A single Suprelorin® 4.7 mg implant suppressed sperm production for 22-25 months. No clinically side effect was observed during the study period. All toms returned to their initial seminal quality 23-28 months after treatment. Therefore, we conclude that Suprelorin® 4.7 mg is a safe option for reversible reproduction control during long periods in tomcats.

Humans are unique among great apes and most other mammals, in that our wide range of offspring investment behaviors includes significant paternal care and provisioning of children. Moreover, hormones play an important role in modulating male paternal investment. Despite a growing body of research on the hormonal associations with paternal care in humans, fathers who self-identify as gay have not received the same level of research attention. We explore associations between hormones that are central to reproductive effort in American gay couples (n = 48 pairs, mean age 36 ± 11 SD years) with and without children. Building on previous investigations of paternal investment, we focus on testosterone and cortisol given their primary roles in the behavioral and metabolic aspects of male reproductive effort. We provide preliminary evidence that gay fathers have lower cortisol levels compared to gay non-fathers. Cortisol and testosterone also positively co-varied in all couples, independent of potential covariates. We did not find evidence for differences in testosterone levels between gay fathers and non-fathers, although sample sizes were limited. Based on this preliminary evidence, we suggest that psychosocial stress among gay fathers may differ compared to gay couples without children, or that the stress response in gay fathers is mitigated in some way compared to non-fathers. These data underscore the importance of human paternal care diversity and the value of inclusivity in human evolutionary behavior research.

Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague⁻Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.