Maternal protein supplementation during mid-gestation improves offspring performance and metabolism in beef cows.

This study examined the impact of maternal protein supplementation during mid-gestation on offspring, considering potential sex-related effects. Forty-three pregnant purebred Tabapuã beef cows (20 female and 23 male fetuses) were collectively managed in a pasture until 100 d of gestation. From 100 to 200 d of gestation, they were randomly assigned to the restricted group [(RES) - basal diet (75% corn silage + 25% sugar cane bagasse + mineral mixture); n = 24] or control group [(CON) - same basal diet + based-plant supplement [40% of crude protein, 3.5 g/kg of body weight (BW); n = 19]. From 200 d of gestation until parturition, all cows were equally fed corn silage and mineral mixture. During the cow-calf phase, cows and their calves were maintained in a pasture area. After weaning, calves were individually housed and evaluated during the backgrounding (255 to 320 d), growing 1 (321 to 381 d), and growing 2 (382 to 445 d) phases. Offspring's blood samples were collected at 210 and 445 d of age. Samples of skeletal muscle tissue were collected through biopsies at 7, 30, and 445 d of age. Muscle tissue samples were subjected to reverse-transcription quantitative polymerase chain reaction analysis. Prenatal treatment and offspring's sex (when pertinent) were considered fixed effects. The significance level was set at 5%. At mid-gestation, cows supplemented with protein reached 98% and 92% of their protein and energy requirements, while nonsupplemented cows attained only 30% and 50% of these requirements, respectively. The RES offspring were lighter at birth (27 vs. 31 kg), weaning (197 vs. 214 kg), and 445 d of age (398 vs. 429 kg) (P ≤ 0.05). The CON calves had greater (P < 0.05) morphometric measurements overall. The CON offspring had ~26% greater muscle fiber area (P ≤ 0.01). There was a trend (P = 0.06) for a greater Mechanistic target of rapamycin kinase mRNA expression in the Longissimus thoracis in the CON group at 7 d of age. The Myogenic differentiation 1 expression was greater (P = 0.02) in RES-females. Upregulation of Carnitine palmitoyltransferase 2 was observed in RES offspring at 445 d (P = 0.04). Expression of Fatty acid binding protein 4 (P < 0.001), Peroxisome proliferator-activated receptor gamma (P < 0.001), and Stearoyl-Coenzyme A desaturase (P < 0.001) was upregulated in CON-females. Therefore, protein supplementation during gestation enhances offspring growth and promotes favorable responses to lipogenesis, particularly in females.

In tropical conditions, beef cows on pasture often experience protein restriction during mid-to-late gestation, potentially impacting offspring development negatively. To address this, we investigated the effects of strategic protein supplementation for pregnant beef cows fed low-quality forage during mid-gestation on the postnatal growth trajectory of their offspring. The supplementation program, implemented during mid-gestation, increased dry matter intake by addressing nitrogen deficiency in the rumen, resulting in meeting 98% and 92% of protein and energy requirements in supplemented cows. In contrast, nonsupplemented cows met only 30% and 50% of these requirements, respectively. Consequently, protein supplementation positively influenced the postnatal growth trajectory of the offspring, attributed to beneficial changes in secondary myogenesis and hypertrophy processes. Supplementing cows with crude protein also stimulated lipogenesis, potentially contributing to intramuscular fat deposition, particularly in females. Therefore, this study emphasizes the importance of nutritional interventions for pregnant beef cows fed low-quality forage.

Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease.

BACKGROUND: With the development of modern medicine, the Traditional Chinese Medicine (TCM) combined with western medicine began to be produced and applied. Scalp acupuncture (SA) as a Chinese medicine based on neurological theory, has a great advantage compared with TCM in the treatment of nervous system diseases. METHOD: In this paper, we analyze the physiological and pathological manifestations of sexual dimorphism (SD) to illustrate the necessity of SD treatment. In addition, we review the factors that can affect SD and analyze in physiological structure, function, and pathological neurons. Diseases (pathological basis, pathological manifestations, and incidence) and factors leading to gender differences, which to analyze the possibility of gender differences in SA. RESULT: Furthermore, we creatively a new insight of SD-SA and provide the complete SD treatment cases on the basis of the existing SA in different kinds of diseases including stroke, migraine, attention deficit hyperactivity disorder (ADHD), and depression. CONCLUSION: In summary, we believe that it is feasible to improve the clinical effectiveness of SA, which is able to promote the development of SA, and then provides an actionable evidence for the promotion of precision medicine in the future.

Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism.

Background & Aims: The constitutive androstane receptor (CAR) is a nuclear receptor that binds diverse xenobiotics and whose activation leads to the modulation of the expression of target genes involved in xenobiotic detoxification and energy metabolism. Although CAR hepatic activity is considered to be higher in women than in men, its sex-dependent response to an acute pharmacological activation has seldom been investigated. Methods: The hepatic transcriptome, plasma markers, and hepatic metabolome, were analysed in Car+/+ and Car-/- male and female mice treated either with the CAR-specific agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or with vehicle. Results: Although 90% of TCPOBOP-sensitive genes were modulated in a sex-independent manner, the remaining 10% showed almost exclusive female liver specificity. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation, and extracellular matrix organisation. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Hepatic expression of flavin monooxygenase 3 (Fmo3) was almost abolished and was associated with a decrease in hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a potential role in the control of TMAO homeostasis, CAR activation decreased platelet hyper-responsiveness in female mice supplemented with dietary choline. Conclusions: More than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic responses such as platelet aggregation. CAR activation may be an important mechanism of sexually-dimorphic drug-induced liver injury. Impact and implications: CAR is activated by many drugs and pollutants. Its pharmacological activation had a stronger impact on hepatic gene expression and metabolism in females than in males, and had a specific impact on liver toxicity and trimethylamine metabolism. Sexual dimorphism should be considered when testing and/or prescribing xenobiotics known to activate CAR.

Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains.

BACKGROUND: ESR2, a nuclear estrogen receptor also known as estrogen receptor ß, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506). METHODS: To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch's t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey-Kramer test were used for comparisons among multiple groups with different estrogen treatments. RESULTS: ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers. CONCLUSIONS: Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain.

Although the brain is a major target organ of estrogens, the distribution of estrogen receptors in the brain is not fully understood. ESR2, also known as estrogen receptor ß, is an estrogen receptor subtype; its localization in the brain has long been controversial because it has traditionally been difficult to detect. In the present study, we analyzed the expression sites of ESR2 in mouse and rat brains using immunohistochemistry with a well-validated antibody, PPZ0506. The immunohistochemical analysis revealed a more localized expression of ESR2 protein in brain subregions than has previously been reported. Additionally, there were clear sex and interspecies differences in the distribution of this protein. We also observed changes in ESR2 expression in the female brain in response to circulating estrogen levels. Our results, which show the precise expression profiles of ESR2 protein in rodent brains, will be helpful for understanding the ESR2-mediated actions of estrogen.

Influence of sexual dimorphism and dichromatism on reproductive success in a rare native cactus.

Identifying plant sexual dimorphic traits is critical in advancing our knowledge on plant-pollinator interactions. For example, dimorphism in floral colors, or sexual dichromatism, is a crucial mediator of pollinator choice on foraging decisions. We studied Cylindropuntia wolfii, a model system, with diverse flower colors and a functionally dioecious sexual system. However, evidence suggests that sexual reproduction is limited in this species as it has a low seed set especially in naturally pollinated fruits. Thus, it is critical to this native species' conservation to investigate its relationship with pollinators. Our goals were to: (a) investigate the sexual dimorphism including the sexual dichromatism in the flowers of the cactus, and (b) determine whether sexually dimorphic traits affect the pollinator attraction of both the sexes. We measured several quantitative and qualitative traits and compared them between male and female flowers. Then we recorded the pollinator visitation rate in nature for both sexes and tracked pollinator color preference using fluorescent dyes as pollen analogues. Our study showed that male flowers of C. wolfii are bigger and brighter, and they attract more potential pollinators than females, supporting the hypothesis that sexual dimorphism influences pollinator visitation preference. Fluorescence dichromatism, in which female flowers' anthers fluoresce more than male flower anthers suggest this could be female flowers' strategy to compensate for their dark colors and small size. The results from this study showed that C. wolfii exhibits sexual dichromatism and fluorescence dichromatism, which is a novel finding in plant research.

Genistein early in life modifies the arcuate nucleus of the hypothalamus morphology differentially in male and female rats.

In the present work we analyzed the effects of postnatal exposure to two doses of genistein (10 µg/g or 50 µg/g) from postnatal (P) day 6 to P13, on the morphology of the arcuate nucleus (Arc). The analyses of Arc coronal brain sections at 90 days showed that the ArcMP had higher values in volume, Nissl-stained neurons and GPER-ir neurons in males than in females and the treatment with genistein abolished these sex differences in most of the parameters studied. Moreover, in males, but not in females, the GPER-ir neurons decreased in the ArcMP but increased in the ArcL with both doses of genistein. In the ArcLP, GPER-ir population increased with the lowest doses and decreased with the highest one in males. Our results confirm that the Arc subdivisions have differential vulnerability to the effects of genistein during development, depending on which neuromorphological parameters, dose and sex are analyzed.

Sexual dimorphism in selenium deficiency is associated with metabolic syndrome and prevalence of heart disease.

BACKGROUND: Serum selenium levels have been associated with the incidence of heart failure (HF) and signs of the metabolic syndrome. In addition, notable differences have been reported between males and females in food intake and micronutrient metabolism, possibly explaining different health outcomes. OBJECTIVE: Our objective was to elucidate sex-specific, cross-sectional phenotypic differences in the association of serum selenium concentrations with parameters of metabolic syndrome and HF. METHODS: We investigated data from individuals from a community-based cohort (PREVEND; N = 4288) and heart failure cohort (BIOSTAT-CHF; N = 1994). In both populations, cross-sectional analyses were performed for potential interaction (p < 0.1) between sex and serum selenium with overlapping signs and clinical parameters of the metabolic syndrome and HF. RESULTS: Baseline selenium levels of the total cohort were similar between PREVEND (85.7 µg/L) and BIOSTAT-CHF (89.1 µg/L). Females with lower selenium levels had a higher BMI and increased prevalence of diabetes than females with higher selenium, in both PREVEND (pinteraction < 0.001; pinteraction = 0.040, resp.) and BIOSTAT-CHF (pinteraction = 0.021; pinteraction = 0.024, resp.), while opposite associations were observed for males. Additionally, in females, but not in males, lower selenium was associated with a higher prevalence of myocardial infarction (MI) in PREVEND (pinteraction = 0.021) and BIOSTAT-CHF (pinteraction = 0.084). CONCLUSION: Lower selenium was associated with a higher BMI and increased prevalence of diabetes in females, opposite to males, and was also associated with more MI in females. Interventional studies are needed to validate this observation.

Sex and age differences in the distribution of estrogen receptors in mice.

Estrogen receptors (ERα and ERß) are crucial for the regulation of socio-sexual behaviors and the organization of sex-specific neural networks in the developing brain. However, how the distribution patterns of ERα and ERß change throughout life is unclear. Using genetically modified ERß-RFPtg mice, we investigated the distribution of ERα, ERß, and their colocalization in the ventromedial nucleus of the hypothalamus (VMH), anteroventral periventricular nucleus (AVPV), and bed nucleus of stria terminalis (BNST) from postnatal days (PD) 0 to 56. ERα expression was higher in females that showed an increase after PD14 in all brain regions, whereas ERß-RFP expression pattern was markedly different among the regions. In the VMH, ERß-RFP was highly expressed on PD0 and PD7 but decreased drastically to very low expression afterward in both sexes. In contrast, ERß-RFP expression was higher in females compared to males in the AVPV but lower in the BNST throughout life especially late- and post-pubertal periods. Our results demonstrating that ERα and ERß-RFP expression changed in a sex-, age- and region-specific manner contribute to further clarification of the mechanisms underlying estrogen-dependent organization of the brain in both sexes.

Maternal omega-3 LC-PUFA supplementation programs an improved bone mass in the offspring with a more pronounced effect in females than males at adulthood.

Early balanced nutrition is vital in achieving optimal skeletal mass and its maintenance. Although a lower omega-6 (n-6): omega-3 (n-3) long-chain polyunsaturated fatty acid (LC-PUFA) ratio is strongly linked with bone health, its maternal effect in the programming of the offspring's skeleton remains to be elucidated. Plugged C57BL/6 mice were fed either n-3 LC-PUFA Enriched Diet (LED) or a control diet (C) throughout their gestation and lactation. Offspring born to both the groups were weaned onto C till 6, 12, and 24 weeks of their age. Offspring's skeleton metabolism and serum fatty acid composition was studied. In humans, seventy-five mother-female newborns pairs from term gestation were tested for their maternal LC-PUFA status relationships to venous cord blood bone biomarkers. Offspring of maternal LED supplemented mice exhibited a superior bone phenotype over C, more prominent in females than males. A lower serum n-6/n-3 LC-PUFA in the LED group offspring was strongly associated with blood biomarkers of bone metabolism. Sexual dimorphism evidenced had a strong correlation between offspring's LC-PUFA levels and bone turnover markers in serum. A higher potential for osteoblastic differentiation in both LED offspring genders and reduced osteoclastogenesis in females was cell-autonomous effect. The human cross-sectional study also showed a positive correlation between maternal n-3 PUFA and cord blood markers of bone formation in female newborns at birth. Maternal dietary n-6/ n-3 fat quality determines offspring's bone growth and development. Our data suggest that the skeleton of female offspring is likely to be more sensitive to this early exposure.

Perinatal exposure to tributyltin affects feeding behavior and expression of hypothalamic neuropeptide Y in the paraventricular nucleus of adult mice.

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance. We have previously demonstrated that adult exposure to TBT altered the expression of neuropeptides in the hypothalamus. In this study, we orally administered daily a solution containing oil, or TBT (0.25, 2.5, or 25 µg/kg body weight/day) to pregnant females from gestational day 8 until birth, and to their pups from day 0 until post-natal day 21. Our results showed that TBT exposure of female mice during gestation and of pups during lactation permanently altered the feeding efficiency of pups of both sexes and subcutaneous fat distribution in adult males. In addition, the neuropeptide Y system was affected at the level of the paraventricular nucleus, with a decrease in immunoreactivity in both sexes (significant in females for all TBT doses and in males only for intermediate TBT doses), while no effect was observed in other hypothalamic areas (arcuate, ventromedial and dorsomedial nuclei). Metabolic syndrome, as well as obesity and diabetes, which are significant health issues, are considered multifactorial diseases and may be caused by exposure to metabolic disruptors, both in adults and during perinatal life. In addition, our work indicates that TBT doses defined as the tolerably daily intake had a profound and sex-specific long-term effect.

Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF / 中山大学学报(医学科学版)

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 10 mice/group, half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

Transcriptome Sequencing and Comparison of Venom Glands Revealed Intraspecific Differentiation and Expression Characteristics of Toxin and Defensin Genes in Mesobuthus martensii Populations.

Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern China with complex habitats. It possesses several kinds of toxins that can regulate different ion channels and serve as crucial natural drug resources. Extensive and in-depth studies have been performed on the structures and functions of toxins of M. martensii. In this research, we compared the morphology of M. martensii populations from different localities and calculated the COI genetic distance to determine intraspecific variations. Transcriptome sequencing by RNA-sequencing of the venom glands of M. martensii from ten localities and M. eupeus from one locality was analyzed. The results revealed intraspecific variation in the expression of sodium channel toxin genes, potassium channel toxin genes, calcium channel toxin genes, chloride channel toxin genes, and defensin genes that could be related to the habitats in which these populations are distributed, except the genetic relationships. However, it is not the same in different toxin families. M. martensii and M. eupeus exhibit sexual dimorphism under the expression of toxin genes, which also vary in different toxin families. The following order was recorded in the difference of expression of sodium channel toxin genes: interspecific difference; differences among different populations of the same species; differences between sexes in the same population, whereas the order in the difference of expression of potassium channel toxin genes was interspecific difference; differences between both sexes of same populations; differences among the same sex in different populations of the same species. In addition, there existed fewer expressed genes of calcium channel toxins, chloride channel toxins, and defensins (no more than four members in each family), and their expression differences were not distinct. Interestingly, the expression of two calcium channel toxin genes showed a preference for males and certain populations. We found a difference in the expression of sodium channel toxin genes, potassium channel toxin genes, and chloride channel toxin genes between M. martensii and M. eupeus. In most cases, the expression of one member of the toxin gene clusters distributed in series on the genome were close in different populations and genders, and the members of most clusters expressed in same population and gender tended to be the different. Twenty-one toxin genes were found with the MS/MS identification evidence of M. martensii venom. Since scorpions were not subjected to electrical stimulation or other special treatments before conducting the transcriptome extraction experiment, the results suggested the presence of intraspecific variation and sexual dimorphism of toxin components which revealed the expression characteristics of toxin and defensin genes in M. martensii. We believe this study will promote further in-depth research and use of scorpions and their toxin resources, which in turn will be helpful in standardizing the identification and medical applications of Quanxie in traditional Chinese medicine.

Rapid divergence in vegetative morphology of a wind-pollinated plant between populations at contrasting densities.

Plant sexual dimorphism is thought to evolve in response to sex-specific selection associated with competition for access to mates or resources, both of which may be density dependent. In wind-pollinated plants in particular, vegetative traits such as plant size and architecture may influence resource acquisition and both pollen dispersal and receipt, with potential conflict between these two components of fitness. We evaluated the role of plant density in shaping plant traits by measuring evolutionary responses in experimental populations of the sexually dimorphic wind-pollinated plant Mercurialis annua. After three generations of evolution, we observed divergence between high- and low-density populations in several vegetative traits, whereas there was no divergence for reproductive traits. A reversal in the direction of sexually dimorphic traits expressed in young plants evolved in both low- and high-density populations compared to the original population (stored as seeds). Compared to the source population, males at high density evolved to be taller when young, whereas at low density young females tended to become smaller. These results demonstrate that a simple change in plant density can induce age-dependent and sex-specific evolution in the ontogeny of vegetative organs, and illustrates the power of experimental evolution for investigating plant trait evolution.

Intersexual flower differences in an andromonoecious species: small pollen-rich staminate flowers under resource limitation.

Andromonoecy, the presence of perfect and staminate flowers in the same individual, has evolved repeatedly in angiosperms. The staminate flowers are generally smaller than the perfect flowers in species that produce staminate flowers plastically when resources are limited. The smaller staminate flowers are expected to be less attractive to pollinators and have reduced size-matching with pollinators than perfect flowers. We hypothesized that these potential disadvantages of staminate versus perfect flowers facilitate the evolution of sex-specific floral morphology, such as allometric relationship between flower size and male reproductive organ. We compared six floral morphology traits, pollen production, pollinator visits and pollen removal from anthers between staminate and perfect flowers in several natural Commelina communis populations. Nectarless and zygomorphic C. communis flowers have polymorphic stamens with attracting, feeding and pollinating anthers and were visited by diverse pollinators. Staminate flowers were significantly smaller than perfect flowers, despite a large overlap in size between sexes. The lengths of pollinating stamens did not differ between staminate and perfect flowers, and staminate flowers produced significantly more pollen. We observed significantly more pollinator visits to perfect flowers than to staminate flowers. By contrast, pollen removal from pollinating stamens was significantly higher in staminate flowers than in perfect flowers. There is sexual dimorphism in flower morphology in C. communis. Staminate flowers with smaller attraction organs, similar pollinating stamens and higher pollen production assure higher pollen donor success relative to perfect flowers. Our results suggest that the morphological changes in staminate flowers enhance pollination success, even with limited resources.

Subacute and low-dose tributyltin exposure disturbs the mammalian hypothalamus-pituitary-thyroid axis in a sex-dependent manner.

Tributyltin (TBT) is an endocrine disruptor chemical (EDC) capable of altering the proper function of the hypothalamus-pituitary thyroid (HPT) axis. This study aimed to evaluate the subacute effects of TBT on the HPT axis of male and female rats. A dose of 100 ng/kg/day TBT was used in both sexes over a 15-day period, and the morphophysiology and gene expression of the HPT axis were assessed. TBT exposure increased the body weight in both sexes, while food efficiency increased - only in male rats. It was also possible to note alterations in the thyroid, with the presence of a stratified epithelium, cystic degeneration, and increased interstitial collagen deposition. A reduction in T3 and T4 levels was only observed in TBT male rats. A reduction in TSH levels was observed in TBT female rats. Evaluating mRNA expression, we observed a decrease in hepatic D1 and TRH mRNA levels in TBT female rats. An increase in D2 mRNA expression in the hypothalamus was observed in TBT male rats. Additionally, no significant changes in TRH or hepatic D1 mRNA expression in TBT male rats or in hypothalamic D1 and D2 mRNA expression in TBT female rats were observed. Thus, we can conclude that TBT has different toxicological effects on male and female rats by altering thyroid gland morphophysiology, leading to abnormal HPT axis function, and even at subacute and low doses, it may be involved in complex endocrine and metabolic disorders.

Effect of Growth Hormone Secretagogue Receptor Deletion on Growth, Pulsatile Growth Hormone Secretion, and Meal Pattern in Male and Female Mice.

INTRODUCTION: While the vast majority of research investigating the role of ghrelin or its receptor, GHS-R1a, in growth, feeding, and metabolism has been conducted in male rodents, very little is known about sex differences in this system. Furthermore, the role of GHS-R1a signaling in the control of pulsatile GH secretion and its link with growth or metabolic parameters has never been characterized. METHODS: We assessed the sex-specific contribution of GHS-R1a signaling in the activity of the GH/IGF-1 axis, metabolic parameters, and feeding behavior in adolescent (5-6 weeks old) or adult (10-19 weeks old) GHS-R KO (Ghsr-/-) and WT (Ghsr+/+) male and female mice. RESULTS: Adult Ghsr-/- male and female mice displayed deficits in weight and linear growth that were correlated with reduced GH pituitary contents in males only. GHS-R1a deletion was associated with reduced meal frequency and increased meal intervals, as well as reduced hypothalamic GHRH and NPY mRNA in males, not females. In adult, GH release from Ghsr-/- mice pituitary explants ex vivo was reduced independently of the sex. However, in vivo pulsatile GH secretion decreased in adult but not adolescent Ghsr-/- females, while in males, GHS-R1a deletion was associated with reduction in pulsatile GH secretion during adolescence exclusively. In males, linear growth did not correlate with pulsatile GH secretion, but rather with ApEn, a measure that reflects irregularity of the rhythmic secretion. Fat mass, plasma leptin concentrations, or ambulatory activity did not predict differences in GH secretion. DISCUSSION/CONCLUSION: These results point to a sex-dependent dimorphic effect of GHS-R1a signaling to modulate pulsatile GH secretion and meal pattern in mice with different compensatory mechanisms occurring in the hypothalamus of adult males and females after GHS-R1a deletion. Altogether, we show that GHS-R1a signaling plays a more critical role in the regulation of pulsatile GH secretion during adolescence in males and adulthood in females.

Perinatal exposure to high fat diet alters expression of MeCP2 in the hypothalamus.

Obesity is a complex disease that is the result of a number of different factors including genetic, environmental, and endocrine abnormalities. Given that monogenic forms of obesity are rare, it is important to identify other mechanisms that contribute to its etiology. Methyl-Cp-G binding protein 2 (MeCP2) is a neuroepigenetic factor that binds to methylated regions of DNA to influence transcription. Past studies demonstrate that disruption in MeCP2 function produces obesity in mice. Using a diet-induced obesity mouse model, we show that perinatal exposure to high fat diet significantly decreases MeCP2 protein expression in the hypothalamus of female mice, effects not seen when high fat diet is given to mice during adulthood. Moreover, these effects are seen specifically in a subregion of the hypothalamus known as the arcuate nucleus with females having decreased MeCP2 expression in rostral areas and males having decreased MeCP2 expression in intermediate regions of the arcuate nucleus. Interestingly, mice gain more weight when exposed to high fat diet during adulthood relative to mice exposed to high fat diet perinatally, suggesting that perhaps high fat diet exposure during adulthood may be affecting mechanisms independent of MeCP2 function. Collectively, our data demonstrate that there are developmentally sensitive periods in which MeCP2 expression is influenced by high fat diet exposure and this occurs in a sexually dimorphic manner.

Ventromedial Nucleus of the Hypothalamus Neurons Under the Magnifying Glass.

The ventromedial nucleus of the hypothalamus (VMH) is a complex brain structure that is integral to many neuroendocrine functions, including glucose regulation, thermogenesis, and appetitive, social, and sexual behaviors. As such, it is of little surprise that the nucleus is under intensive investigation to decipher the mechanisms which underlie these diverse roles. Developments in genetic and investigative tools, for example the targeting of steroidogenic factor-1-expressing neurons, have allowed us to take a closer look at the VMH, its connections, and how it affects competing behaviors. In the current review, we aim to integrate recent findings into the literature and contemplate the conclusions that can be drawn.

Prevalence of the interthalamic adhesion in the human brain: a review of literature.

The interthalamic adhesion (IA) is a midline structure connecting the two thalami. Though it has been studied for centuries its exact function remains elusive. Early studies had noted its peculiar absence even among some healthy individuals. Population studies have investigated the differences in prevalence of IA in pathologic conditions and healthy controls. However, there is a general lack of consensus on IA prevalence in the healthy population. Understanding the true prevalence is critical in providing context for future studies, as well as uncovering further clues regarding IA's function. We systematically reviewed the existing literature to evaluate the prevalence of IA. The average prevalence among reviewed studies was higher than previously reported, at 87.3%. Studies utilizing magnetic resonance imaging rather than cadaveric specimens reported higher rates of IA prevalence. A higher prevalence among females was noted throughout the literature that persisted regardless of acquisition modality utilized.

Differential gene expression patterns during gametophyte development provide insights into sex differentiation in the dioicous kelp Saccharina japonica.

BACKGROUND: In brown algae, dioicy is the prevalent sexual system, and phenotypic differences between male and female gametophytes have been found in many dioicous species. Saccharina japonica show remarkable sexual dimorphism in gametophytes before gametogenesis. A higher level of phenotypic differentiation was also found in female and male gametes after gametogenesis. However, the patterns of differential gene expression throughout gametophyte development and how these changes might relate to sex-specific fitness at the gamete stage in S. japonica are not well known. RESULTS: In this study, differences in gene expression between male and female gametophytes in different developmental stages were investigated using comparative transcriptome analysis. Among the 20,151 genes expressed in the haploid gametophyte generation, 37.53% were sex-biased. The abundance of sex-biased genes in mature gametophytes was much higher than that in immature gametophytes, and more male-biased than female-biased genes were observed in the mature stage. The predicted functions of most sex-biased genes were closely related to the sex-specific characteristics of gametes, including cell wall biosynthesis, sperm motility, and sperm and egg recognition. In addition, 51 genes were specifically expressed in males in both stages, showing great potential as candidate male sex-determining region (SDR) genes. CONCLUSIONS: This study describes a thorough investigation into differential gene expression between male and female gametophytes in the dioicous kelp S. japonica. A large number of sex-biased genes in mature gametophytes may be associated with the divergence of phenotypic traits and physiological functions between female gametes (eggs) and male gametes (sperm) during sexual differentiation. These genes may mainly come from new sex-biased genes that have recently evolved in the S. japonica lineage. The duplication of sex-biased genes was detected, which may increase the number of sex-biased genes after gametogenesis in S. japonica to some extent. The excess of male-biased genes over female-biased genes in the mature stage may reflect the different levels of sexual selection across sexes. This study deepens our understanding of the regulation of sex development and differentiation in the dioicous kelp S. japonica.