Neuroendocrine Axis Research Articles

Ovarian reserve, metabolic and neuroendocrine profiles of cadets from Air Force Academy: a pilot study.

Intensive physical activity and rigid dietary regimes can act as modifiers of neuroendocrine axes in women, inducing hormonal disorders and related menstrual irregularities such as functional hypothalamic amenorrhea (FHA). It would be important to evaluate if such disturbances may worsen female fertility. The aim of this study was to evaluate ovarian reserve markers and neuroendocrine axis in young military academy female cadets with years of training and occurrence of FHA. This is a prospective pilot study involving young female cadets from the Military Academy training program. Ovarian reserve markers and metabolic and neuroendocrine factors in the early follicular phase were measured with blood tests and transvaginal ultrasound. The study group consisted of 11 women belonging to the first year of training and the control group of 33 women belonging to the second to sixth year of training. No differences were found about ovarian reserve markers between the two groups. Moreover, the occurrence of FHA did not modify the ovarian reserve compared to eumenorrhea in both groups. Women from the study group showed significantly higher levels of fasting Insulin (42.18±26.14 uUI/mL versus 11.9±10.2 ng/mL, P value <0.001) and insulin-like growth factor 1 (310.06±67.90 uUI/mL versus 248.67±61.57 uUI/mL, P value = 0.015) compared with control group. Both intense physical training and FHA do not appear to impact the ovarian reserve of young female cadets. Although preliminary, these findings seem reassuring about the reproductive health of these women and their future fertility.

Unveiling the intricacies of irritable bowel syndrome.

Irritable bowel syndrome (IBS) remains a challenging condition both for patients and clinicians, characterized by its chronic nature and the elusive complexity of its underlying mechanisms. The multifaceted relationship between the neuroendocrine axis, gut microbiota, and inflammatory response has emerged as a focal point in recent research, offering new insights into the pathophysiology of IBS. The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut, often referred to as the "gut-brain axis". This bidirectional communication is essential for regulating gastrointestinal function, stress responses, and overall homeostasis. Dysregulation of this axis, as highlighted by elevated cortisol and serotonin levels in IBS patients, suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms. These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS, potentially guiding more effective, personalized treatment approaches. Equally important is the role of the gut microbiota, a diverse and dynamic ecosystem that directly impacts gut health. This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses. These findings align with the growing recognition that gut microbiota is a critical player in IBS, influencing both the disease's onset and progression.

Association Between Intellectual Disability and Hair Cortisol Concentration in Adolescents in a Brazilian Population-Based Birth Cohort.

Children with intellectual disability (ID) usually exhibit neuroendocrine functioning impairment, such as alterations in the hypothalamic-pituitary-adrenal (HPA) neuroendocrine axis, which can result in glucocorticoid cortisol release alterations. Indeed, many studies showed a positive association between ID and cortisol concentration. However, evidence is lacking on the relationship between child neurodevelopment and cortisol levels during adolescence in population-based studies. We aimed to test the association between ID and hair cortisol concentration (HCC) during adolescence in a prospective population-based cohort. Data from 1770 individuals in the 2004 Pelotas Birth Cohort were used. ID was diagnosed at age 6 through clinical examination. Hair cortisol was measured at age 15. Association was assessed using linear regression models adjusted for sex, socio-economic factors, hair-related variables and corticosteroid use. Higher HCC were observed in individuals with ID (β: 1.120; 95% CI: 1.012, 1.241) in the analysis adjusted for sex, hair-related variables and corticosteroid use. Compared to the other aetiological groups, this was more evident in idiopathic ID. But this did not remain significant when demographics/socio-economic variables were controlled for. Children with ID, particularly those with idiopathic ID, might exhibit dysfunction in the HPA axis or experience heightened stress levels during adolescence.

Growth Hormone Receptor in Lateral Hypothalamic Neurons Is Required for Increased Food-Seeking Behavior during Food Restriction in Male Mice.

Growth hormone (GH) action in the brain regulates neuroendocrine axes, energy and glucose homeostasis, and several neurological functions. The lateral hypothalamic area (LHA) contains numerous neurons that respond to a systemic GH injection by expressing the phosphorylated STAT5, a GH receptor (GHR) signaling marker. However, the potential role of GHR signaling in the LHA is unknown. In this study, we demonstrated that ∼70% of orexin- and leptin receptor (LepR)-expressing neurons in the LHA are responsive to GH. Male mice carrying inactivation of the Ghr gene in the LHA were generated via bilateral injections of an adeno-associated virus. In ad libitum-fed mice, GHR ablation in LHA neurons did not significantly change energy and glucose homeostasis. Subsequently, mice were subjected to 5 d of 40% food restriction. Food restriction decreased body weight, energy expenditure, and carbohydrate oxidation. These effects were similarly observed in control and LHAΔGHR mice. While food-deprived control mice progressively increased ambulatory/exploratory activity and food-seeking behavior, LHAΔGHR mice did not show hyperactivity induced by food restriction. GHR ablation in the LHA reduced the percentage of orexin neurons expressing c-Fos during food restriction. Additionally, an acute GH injection increased the expression of c-Fos in LHAORX neurons. Inactivation of Ghr in LepR-expressing cells did not prevent hyperactivity in food-deprived mice, whereas whole-brain Ghr knock-out mice showed reduced ambulatory activity during food restriction. Our findings indicate that GHR signaling in the LHA regulates the activity of orexin neurons and is necessary to increase food-seeking behavior in food-deprived male mice.

Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome.

This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Evaluating the gonads of left-handed children using ultrasonography and comparing the findings with those of right-handed ones.

Lateralization affected gonad size in girls. In boys, gonads were not affected by lateralization. Cerebral lateralization may affect the hypothalamic-pituitary-gonadal axis in girls. • Hand use varies according to which cerebral hemisphere is dominant. Males tend to be more left-handed than females. Brain asymmetry can affect the neuroendocrine axis. • Ultrasonographic gonadal dimensions were examined in left-handed and right-handed children. Cerebral lateralization may affect the hypothalamic-pituitary-gonadal axis in girls.

Emerging roles of lipid and metabolic sensing in the neuroendocrine control of body weight and reproduction.

The hypothalamus lies at the intersection of brain and hormonal mechanisms governing essential bodily functions, including metabolic/body weight homeostasis and reproduction. While metabolism and fertility are precisely regulated by independent neuroendocrine axes, these are tightly connected, as reflection of the bidirectional interplay between the energy status of the organisms and their capacity to reproduce; a connection with important pathophysiological implications in disorders affecting these two crucial systems. Beyond the well-characterized roles of key hormones (e.g., leptin, insulin, ghrelin) and neuropeptides (e.g., melanocortins, kisspeptins) in the integral control of metabolism and reproduction, mounting evidence has pointed out a relevant function of cell energy sensors and lipid sensing mechanisms in the hypothalamic control of metabolism, with prominent roles also for metabolic sensors, such as mTOR, AMPK and SIRT1, in the nutritional regulation of key aspects of reproduction, such as pubertal maturation. We provide herein a synoptic overview of these novel regulatory pathways, with a particular focus on their putative function in the metabolic control of puberty, and delineate new avenues for further exploration of the intricate mechanisms whereby metabolism and reproduction are tightly connected.

Prevention of Neuronal Damage in Brains of Chronic Stress-induced Male Wistar Rats Administering Centella asiatica (L) Urban

Introduction: Physiological and psychological response of an organism to repetitive stimulus leads to chronic stress which results in depression. This affects the neuro-endocrine axis causing hypersecretion of glucocorticoids which damages the hippocampal neurons in brain through oxidative stress. The body responds by producing Catalase (CAT) an antioxidant found on peroxisomes, which splits the hydrogen peroxide produced by oxidative stress into water and oxygen which are nontoxic, thus offering a protective effect. The synaptic function of the hippocampal neurons is dependent on acetylcholinesterase (AChE) and oxidative stress affects the levels of AChE. The available anti-depressants have the late onset of action and increased toxicity. Centella asiatica (CA), an herb with neuroprotective properties, is known as neuro-tonic and has less toxicity and has been used in ancient traditional medicines. This study aims to examine the neuroprotective effects of crude extract of CA on hippocampal neurons using Nissls stain and levels of AChE and expression of mRNA CAT in the brain tissues of chronic unpredictable mild stress (CUMS)-induced male Wistar rats. Materials and Methods: Thirty-six Male Wistar rats aged 8–10 weeks were held in six groups. One group assigned as control, whereas the other groups were administered CUMS by various stressors, namely restrain, forced swimming in cold water, overnight food and water deprivation, wet bedding, cage tilt at 45°, tail pinching, overcrowding the cages, and change of cage mates randomly for a period of 64 days. One of the stress-induced groups was retained as model group and others were administered crude extracts of CA at the doses of 200, 400, 800, and fluoxetine (Flx) 10 mg/kg body weight. At the end of 64 days, the rats were euthanized and the brain tissue was collected for Nissls staining of the hippocampus, measure levels of AChE using ELISA and expression of mRNA CAT levels using RT-PCR. Results: The rats of the model group exhibited reduced number of viable neurons in the hippocampus as observed in Nissls stain, reduced levels of AChE, and reduced expression of mRNA CAT in the brain tissue while the rat groups receiving CA showed increase in the number of viable neurons, increase in level of AChE, and increase in the expression of mRNA CAT in the brain tissues. The results were comparable to that of Flx. Conclusion: CA effectively attenuates CUMS-induced neuronal loss in the hippocampus of the rat’s brain, normalizes AChE levels, and also the expression of mRNA CAT antioxidant levels. CA could be used in the long-term prevention of chronic stress-induced depression.

Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain.Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Bmal1 regulates female reproduction in mice via the hypothalamic-pituitary-ovarian axis.

The hypothalamic-pituitary-gonadal axis (HPG) is the key neuroendocrine axis involved in reproductive regulation. Brain and muscle ARNT-like protein 1 (Bmal1) participates in regulating the metabolism of various endocrine hormones. However, the regulation of Bmal1 on HPG and female fertility is unclear. This study aims to explore the regulation of female reproduction by Bmal1 via the HPG axis in mice. Bmal1-knockout (Ko) mice were generated using the CRISPR/Cas9 technology. The structure, function, and estrous cycle of ovarian in Bmal1 Ko female mice were measured. The key genes and proteins of the HPG axis involved in regulating female reproduction were examined through transcriptome analysis and then verified by RT-PCR, immunohistochemistry, and western blot. Furthermore, the fertility of female mice was detected after intervening prolactin (PRL) and progesterone (Pg) in Bmal1 ko mice. The number of offspring and ovarian weight were significantly lower in Bmal1-Ko mice than in wild-type (Wt) mice. In Bmal1-Ko mice, ovarian cells were arranged loosely and irregularly, and the total number of follicles was significantly reduced. No corpus luteum was found in the ovaries. Vaginal smears revealed that Bmal1-Ko mice had an irregular estrus cycle. In Bmal1-Ko mice, Star expression was decreased, PRL and luteinizing hormone (LH) levels were increased, and dopamine (DA) and Pg levels were decreased. Inhibition of PRL partially recovered the estrous cycle, corpus luteum formation, and Star expression in the ovaries. Pg supplementation promoted embryo implantation in Bmal1-Ko female mice. Bmal1 Ko increases serum PRL levels in female mice likely by reducing DA levels, thus affecting luteal formation, resulting in decreased Star expression and Pg production, hindering female reproduction. Inhibition of PRL or restoration of Pg can partially restore reproductive capacity in female Bmal1-Ko mice. Thus, Bmal1 may regulate female reproduction via the HPG axis in mice, suggesting that Bmal1 is a potential target to treat female infertility.

Characterization of the interplay between the neuroendocrine stress axes and metabolic diseases

Characterization of the interplay between the neuroendocrine stress axes and metabolic diseases

Androgen regulation of behavioral stress responses and the hypothalamic-pituitary-adrenal axis

Testosterone is a powerful steroid hormone that can impact the brain and behavior in various ways, including regulating behavioral and neuroendocrine (hypothalamic-pituitary-adrenal (HPA) axis) stress responses. Early in life androgens can act to alter development of brain regions associated with stress regulation, which ultimately impacts the display of stress responses later in life. Adult circulating androgens can also influence the expression of distinct genes and proteins that regulate stress responses. These changes in the brain are hypothesized to underlie the potent effects of androgens in regulating behaviors related to stress and stress-induced activation of the HPA axis. Androgens can induce alterations in these functions through direct binding to the androgen receptor (AR) or following conversion to estrogens and subsequent binding to estrogen receptors including estrogen receptor alpha (ERα), beta (ERβ), and G protein-coupled estrogen receptor 1 (GPER1). In this review, we focus on the role of androgens in regulating behavioral and neuroendocrine stress responses at different stages of the lifespan and the sex hormone receptors involved in regulating these effects. We also review the specific brain regions and cell phenotypes upon which androgens are proposed to act to regulate stress responses with an emphasis on hypothalamic and extended amygdala subregions. This knowledge of androgen effects on these neural systems is critical for understanding how sex hormones regulate stress responses.

The Association between Functional Dyspepsia and Metabolic Syndrome-The State of the Art.

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain-gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.

The Water Element, Zang-fu Kidney and Jin Gui Shen Qi Wan

The Water Element, as part of the Traditional Chinese Medicine (TCM) Five Elements, is associated with winter, coldness, darkness and the Zang-fu organs Kidney and Bladder. The TCM Kidney, encompasses far more than the Western concept of an organ which produces and excretes the waste product urine. It controls water and fluid metabolism; a primordial generator (Ming-men Fire, Essence, Jing, promotes growth, skeleton, marrow, innate constitution); Yin-Yang dynamics (innate Yin and Yang); receives Qi; life functions (sexual behavior, reproduction, neuroendocrine axis, nervous system, urinary system, manufacture Blood, acute sense of hearing, controls the 2 lower orifices, assists respiration); as well as supports good life/living (houses commitment, will power, memory). Diseases of the Kidney can manifest as congenital deficiencies, fearful attitude, pathological changes (Yin and Yang Deficiencies, chronic debilitation), and physiological deficiencies associated with senescence. Some of the more common clinical signs of Kidney (Water Element) disease include renal/reproduction disorders, lumbar pain, hind end weakness, teeth/hair loss, deafness, lassitude, neuroendocrine disorders, asthma, congenital disease and bone disorders. One of the most famous formulas to treat Kidney Yang Deficiency and decline of Ming-men Fire is the classical herbal formula Jin Gui Shen Qi Wan. The strategy of this formula is to tonify Kidney Yin to raise Kidney Yang, (since Yin and Yang are mutually dependent), with the addition of warm herbs to ignite the Fire of Ming-men. From a Chinese medical perspective, Kidney Yang Deficiency syndrome may cause endocrine system disorders, immune-deficiency, neurological, renal, and reproductive disorders. This paper will review the Zang-fu Kidney function, and the classic Chinese herbal medicine, Jin Gui Shen Qi Wan (Kidney Qi Pill from the Golden Cabinet).

Impact of Dietary Probiotics on the Immune and Reproductive Physiology of Pubertal Male Japanese Quail (Coturnix coturnix japonica) Administered at the Onset of Pre-Puberty.

Fertility in males is dependent on the proper production of sperms involving the synchronization of numerous factors like oxidative stress, inflammatory processes, and hormonal regulation. Inflammation associated with oxidative stress is also known to impair sperm function. Nutritional factors like probiotics and prebiotics have the potential benefits to modulate these factors which may enhance male fertility. In the present study, immature male Japanese quail at the beginning of 3rd week were administered with Lactobacillus rhamnosus (L), Bifidobacterium longum (B), and mannan-oligosaccharides (M) through dietary supplementation in individual groups as well as in combinations like LB and MLB. Markers of oxidative stress including SOD and catalase were examined by native PAGE; inflammatory biomarkers (IL-1β, IL-10, and NFκB), apoptotic markers (caspase 3 and caspase 7), steroidal hormones, and their receptors estrogen receptor alpha (ERα) and beta (ERβ) were assessed in testis. The study reveals that dietary supplementation of 1% L, B, and M in combination significantly and positively increases the overall growth of immature male quail specifically testicular weight and gonadosomatic index (GSI). Furthermore, significant improvement in testicular cell size; increased steroidal hormones like testosterone, FSH, and LH levels; increase in SOD, catalase enzymes; decrease in apoptotic factors Caspase 3, Caspase 7 and immune system strength observed indicated by a decrease in expression of IL-1β, NFκB; and increase of IL-10 in testis when LBM was used in combination. These variations are attributed to the increase in testicular estrogen receptors alpha and beta, facilitated by the neuroendocrine gonadal axis, ultimately leading to improved male fertility. It can be concluded that the dietary supplementation in combination with L, B, and M enhances male fertility in immature quail by increased expression of estrogen receptors via gut microbiota modulation. It also sheds light on the potential use of these nutritional factors in avian species as therapeutic interventions to overcome low fertility problems in quail thereby benefitting the poultry industry.

Sensitivity of the Neuroendocrine Stress Axis in Metabolic Diseases.

Metabolic diseases are prevalent in modern society and have reached pandemic proportions. Metabolic diseases have systemic effects on the body and can lead to changes in the neuroendocrine stress axis, the critical regulator of the body's stress response. These changes may be attributed to rising insulin levels and the release of adipokines and inflammatory cytokines by adipose tissue, which affect hormone production by the neuroendocrine stress axis. Chronic stress due to inflammation may exacerbate these effects. The increased sensitivity of the neuroendocrine stress axis may be responsible for the development of metabolic syndrome, providing a possible explanation for the high prevalence of severe comorbidities such as heart disease and stroke associated with metabolic disease. In this review, we address current knowledge of the neuroendocrine stress axis in response to metabolic disease and discuss its role in developing metabolic syndrome.

Puberty in beef heifers: effects of prenatal and postnatal nutrition on the development of the neuroendocrine axis.

Reproductive maturation is a complex physiological process controlled by the neuroendocrine system and is characterized by an increase in gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) pulsatile secretion. Nutrition during early development is a key factor regulating puberty onset, which is defined as first ovulation in females. In heifers, nutrient restriction after weaning delays puberty, whereas elevated levels of nutrition and energy reserves advance reproductive maturation. Recent studies in cattle and other animal models have shown that the dam's nutrition during gestation can also program the neuroendocrine system in the developing fetus and has the potential to alter timing of puberty in the offspring. Among the metabolic signals that modulate brain development and control timing of puberty is leptin, a hormone produced primarily by adipocytes that communicates energy status to the brain. Leptin acts within the arcuate nucleus of the hypothalamus to regulate GnRH secretion via an upstream network of neurons that includes neurons that express neuropeptide Y (NPY), an orexigenic peptide with inhibitory effects on GnRH secretion, and alpha melanocyte-stimulating hormone (αMSH), an anorexigenic peptide with excitatory effects on GnRH neurons. Another important population of neurons are KNDy neurons, neurons in the arcuate nucleus that co-express the neuropeptides kisspeptin, neurokinin B, and dynorphin and have strong stimulatory effects on GnRH secretion. Our studies in beef heifers indicate that increased nutrition between 4 to 8 months of age advances puberty by diminishing NPY inhibitory tone and by increasing excitatory inputs of αMSH and kisspeptin, which collectively lead to increased GnRH/LH pulsatility. Our ongoing studies indicate that different planes of nutrition during gestation can alter maternal leptin concentrations and promote changes in the fetal brain. Nonetheless, at least in Bos indicus-influenced heifers, deficits programmed prenatally can be overcome by adequate postnatal nutrition without negatively impacting age at puberty or subsequent fertility.

TAC3 regulates GnRH/gonadotropin synthesis in female chickens

Neurokinin B (NKB), a peptide encoded by the tachykinin 3 (TAC3), is critical for reproduction in all studied species. However, its potential roles in birds are less clear. Using the female chicken (c-) as a model, we showed that cTAC3 is composed of five exons with a full-length cDNA of 787 bp, which was predicted to generate the mature NKB peptide containing 10 amino acids. Using cell-based luciferase reporter assays, we demonstrated that cNKB could effectively and specifically activate tachykinin receptor 3 (TACR3) in HEK293 cells, suggesting its physiological function is likely achieved via activating cTACR3 signaling. Notably, cTAC3 and cTACR3 were predominantly and abundantly expressed in the hypothalamus of hens and meanwhile the mRNA expression of cTAC3 was continuously increased during development, suggesting that NKB-TACR3 may emerge as important components of the neuroendocrine reproductive axis. In support, intraperitoneal injection of cNKB could significantly promote hypothalamic cGnRH-Ι, and pituitary cFSHβ and cLHβ expression in female chickens. Surprisingly, cTAC3 and cTACR3 were also expressed in the pituitary gland, and cNKB treatment significantly increased cLHβ and cFSHβ expression in cultured primary pituitary cells, suggesting cNKB can also act directly at the pituitary level to stimulate gonadotropin synthesis. Collectively, our results reveal that cNKB functionally regulate GnRH/gonadotropin synthesis in female chickens.

Non-monotonic effects of Bisphenol A Dimethacrylate on male mouse reproductive system and fertility leads to impaired conceptive performance

As an estrogenic agent, Bisphenol A Dimethacrylate (Bis-DMA) may incite alterations in both the reproductive tract and the neuroendocrine axis, and thus have the potential to affect the proper development, maturity and conceptive performance in animals. We investigated the consequences of 14 weeks of exposure to different concentrations of Bis-DMA on male mouse conceptive performance. Male mice were exposed to Bis-DMA (0, 0.1 mg/L, 1.0 mg/L or 10 mg/L) via drinking water, and the effects on fertility, reproductive organ weights, reproductive hormone levels, sperm counts and testicular histology were assessed. We clearly demonstrate that prolonged exposure of male mice to Bis-DMA negatively affects fertility and reproduction causing significant reductions in sperm counts, non-monotonic effects on serum LH and testosterone levels, increased seminal vesicle weights, lower number of embryonic implantations and viable fetuses, as well as, increased embryonal resorptions in females mated by Bis-DMA treated males. Furthermore, Bis-DMA caused abnormalities in testicular infrastructure with atrophic seminiferous tubules exhibiting intraepithelial vacuolization and disorganization, loss and shedding of germ cells into the lumen, and presence of apoptotic cells. Our data collectively suggest that Bis-DMA adversely affects male fertility and reproduction by interference with normal hormone signaling in the testis, inducing changes in testicular infrastructure and ultimately leading to impaired reproductive function and fertility.

24 Effects of Gestational and Postweaning Nutrition on Brain Development and Puberty in Beef Heifers

Abstract Approximately 5 million beef heifers enter the U.S. cow herd annually, and their lifetime productivity is largely dependent upon their ability to attain puberty and produce a calf by 24 mo of age. However, a considerable proportion of heifers within existing U.S. production systems fail to achieve these goals, particularly in southern regions where Bos indicus-influenced cattle predominate. Consequently, managerial approaches are needed that employ nutritional programming of the reproductive neuroendocrine axis, while minimizing feeding costs and optimizing the consistent attainment of puberty by approximately 14 mo of age. Our previous research has clearly demonstrated that increased BW gain between 4 and 8 mo of age facilitates pubertal development by programming hypothalamic centers that regulate gonadotropin releasing-hormone (GnRH) secretion. Among the different metabolic hormones, leptin has a critical role in conveying nutritional information to the hypothalamus and controlling puberty. Two hypothalamic neuronal populations that express the orexigenic peptide neuropeptide Y (NPY) and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH; a product of the POMC gene) are key components of afferent pathways that convey inhibitory (NPY) and excitatory (αMSH) inputs to GnRH and kisspeptin neurons. Our studies have demonstrated that short-term increases in dietary energy intake after early weaning at 4 mo of age result in epigenetic, structural, and functional modifications in these hypothalamic pathways to promote high-frequency, episodic release of GnRH and luteinizing hormone. However, integrating the foundational knowledge of metabolic imprinting of the brain for early puberty with issues related to lifetime performance is complex. One approach has been to employ a novel stair-step nutritional regimen involving alternating periods of dietary energy-restriction and re-feeding during juvenile development. This approach is designed to support early onset of puberty by imprinting functional alterations in the hypothalamus during key periods of brain development while optimizing other aspects of growth and performance. Finally, while several key processes of fetal brain development occur during late gestation, neither maternal undernutrition (BCS 3.0-3.5) nor maternal obesity (BCS 7.5-8.0) during the last two trimesters of gestation impacted the organization of hypothalamic neurocircuitries controlling GnRH/LH secretion or age at puberty in the heifer offspring. Collectively, these results indicate that the adult reproductive phenotype in Bos indicus-influenced females is resilient to significant degrees of nutritional stress imposed during prenatal development, particularly if early gestation (first trimester) is avoided. These findings are in contrast with reports in Bos taurus females in which late gestation nutritional extremes result in delayed puberty in heifer offspring, suggesting that potential genotype-specific differences may exist. Research support: USDA-NIFA-AFRI (2018-67015-27595 and 2021-67015-33676).