scholarly journals X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shaohua Qi ◽  
Abdullah Al Mamun ◽  
Conelius Ngwa ◽  
Sharmeen Romana ◽  
Rodney Ritzel ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
X Chromosome ◽  
Epigenetic Modification ◽  
Artery Occlusion ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Young Females ◽  
Human Stroke ◽  
Histone H3k4 ◽  
Cerebral Artery Occlusion

Abstract Background Stroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E2). However, there are also genetic and epigenetic effects of X chromosome dosage that contribute to stroke sensitivity and neuroinflammation after injury, especially in the aged. Genes that escape from X chromosome inactivation (XCI) contribute to sex-specific phenotypes in many disorders. Kdm5c and kdm6a are X escapee genes that demethylate H3K4me3 and H3K27me3, respectively. We hypothesized that the two demethylases play critical roles in mediating the stroke sensitivity. Methods To identify the X escapee genes involved in stroke, we performed RNA-seq in flow-sorted microglia from aged male and female wild type (WT) mice subjected to middle cerebral artery occlusion (MCAO). The expression of these genes (kdm5c/kdm6a) were confirmed in four core genotypes (FCG) mice and in post-mortem human stroke brains by immunohistochemistry (IHC), Western blot, and RT-PCR. Chromatin immunoprecipitation (ChIP) assays were conducted to detect DNA levels of inflammatory interferon regulatory factor (IRF) 4/5 precipitated by histone H3K4 and H3K27 antibodies. Manipulation of kdm5c/kdm6a expression with siRNA or lentivirus was performed in microglial culture, to determine downstream pathways and examine the regulatory roles in inflammatory cytokine production. Results Kdm5c and kdm6a mRNA levels were significantly higher in aged WT female vs. male microglia, and the sex difference also existed in ischemic brains from FCG mice and human stroke patients. The ChIP assay showed the IRF 4/5 had higher binding levels to demethylated H3K4 or H3K27, respectively, in female vs. male ischemic microglia. Knockdown or over expression of kdm5c/kdm6a with siRNA or lentivirus altered the methylation of H3K4 or H3K27 at the IRF4/5 genes, which in turn, impacted the production of inflammatory cytokines. Conclusions The KDM-Histone-IRF pathways are suggested to mediate sex differences in cerebral ischemia. Epigenetic modification of stroke-related genes constitutes an important mechanism underlying the ischemic sexual dimorphism.

Evolution of sexually dimorphic characters in peccaries (Mammalia, Tayassuidae)

Paleobiology ◽  
1993 ◽  
Vol 19 (1) ◽  
pp. 52-70 ◽  
Author(s):  
David B. Wright
Keyword(s):  
Sexual Dimorphism ◽  
Epigenetic Modification ◽  
Phenotypic Expression ◽  
Cladistic Analysis ◽  
Phenotypic Correlation ◽  
Sexually Dimorphic ◽  
Canine Tooth ◽  
Arch Width ◽  
Homologous Characters ◽  
Canine Size

Cladistic analysis of osteological and dental characters in a monophyletic group of Miocene and younger tayassuids demonstrates a pattern of changes in the degree of sexual dimorphism in canine tooth diameter and zygomatic arch width, and in phenotypic correlations between these characters. Primitively, tayassuids have canine teeth that are sexually dimorphic and discretely bimodal in size, and zygomatic arches that are narrow in both sexes. Many late Miocene and Pliocene tayassuids have broad, winglike zygomatic processes. In some species, these processes are large in both sexes, but in others, those of females are much smaller than those of males. The presence of large processes in both sexes is primitive relative to the condition of strong sexual dimorphism. In five separate clades, the zygomatic processes of both sexes become reduced in size, and the degree of sexual dimorphism in canine size becomes reduced as well. The pattern is congruent with predictions derived from a theoretical model of the evolution of sexual dimorphism, and it further indicates the emergence of a new phenotypic correlation between two previously uncorrelated characters, canine size and zygoma size. The advent of this new correlation coincides with the advent of pronounced sexual dimorphism in zygomatic processes. Although such a pattern could be explained by genetically modifying phenotypic expression of homologous characters in one sex or the other, an epigenetic modification of expression is equally plausible: the evolution of sexual dimorphism in homologous characters could be accomplished by placing phenotypic expression of an originally monomorphic character under the control of steroid sex hormones. This hypothesis is consistent with evidence from many vertebrate groups, and it provides testable predictions.

scholarly journals Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1052-1065 ◽  
Author(s):  
Jessica M. Adams ◽  
Veronica Otero-Corchon ◽  
Geoffrey L. Hammond ◽  
Johannes D. Veldhuis ◽  
Nathan Qi ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Peak Plasma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Plasma Corticosterone ◽  
Automated System ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Gh Secretion ◽  
Corticosteroid Binding Globulin

Abstract Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (WT) and somatostatin knockout (Sst-KO) mice to determine the role of SST, the principal inhibitor of GH release, in the generation of sexually dimorphic GH pulsatility. WT males had lower mean and median GH values, less random GH secretory bursts, and longer trough periods between GH pulses than WT females. Each of these parameters was feminized in male Sst-KO mice, whereas female Sst-KO mice had higher GH levels than all other groups, but GH pulsatility was unaffected. We next performed hepatic mRNA profiling with high-density microarrays. Male Sst-KO mice exhibited a globally feminized pattern of GH-dependent mRNA levels, but female Sst-KO mice were largely unaffected. Among the differentially expressed female-predominant genes was Serpina6, which encodes corticosteroid-binding globulin (CBG). Increased CBG was associated with elevated diurnal peak plasma corticosterone in unstressed WT females and both sexes of Sst-KO mice compared with WT males. Sst-KO mice also had exaggerated ACTH and corticosterone responses to acute restraint stress. However, consistent with their lack of phenotypic signs of excess glucocorticoids, cerebrospinal fluid concentrations of free corticosterone in Sst-KO mice were not elevated. In summary, SST is necessary for the prolonged interpulse troughs that define masculinized pituitary GH secretion. SST also contributes to sexual dimorphism of the hypothalamic-pituitary-adrenal axis via GH-dependent regulation of hepatic CBG production.

scholarly journals Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone

2006 ◽  
Vol 36 (2) ◽  
pp. 239-245 ◽  
Author(s):  
J M Torres ◽  
E Ortega
Keyword(s):  
Sexual Dimorphism ◽  
Adult Female ◽  
Male Rat ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Female Rat ◽  
Adult Male Rat ◽  
The Central Nervous System ◽  
New Research

The enzyme 5α-reductase (5α-R) (EC 1.3.99.5) exists as two isoforms, 5α-R type 1 (5α-R1) and 5α-R type 2 (5α-R2). 5α-R1 has been associated with catabolic functions whereas 5α-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5α-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5α-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5α-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5α-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5α-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.

Expression of neurocan after transient middle cerebral artery occlusion in adult rat brain

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S217-S217
Author(s):  
Kentaro Deguchi ◽  
Mikiro Takaishi ◽  
Takeshi Hayashi ◽  
Atsuhiko Oohira ◽  
Shoko Nagotani ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Rat Brain ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Cerebral Artery Occlusion

Comparative assessment of average clinical smile parameters in male and female patients with orthognathic occlusion

2020 ◽  
Vol 25 (2) ◽  
pp. 121-126
Author(s):  
V. G. Galonsky ◽  
N. V. Tarasova ◽  
V. V. Aliamovskii ◽  
I. S. Leonovich
Keyword(s):  
Sexual Dimorphism ◽  
Male And Female ◽  
Young Males ◽  
Young Females ◽  
Female Patients ◽  
Evaluation Of Parameters ◽  
Distinguishing Features ◽  
Vertical Size ◽  
Relative Concept ◽  
The Ideal

Relevance. Separate issues in anthropomorphic sizes of relative norm of the ideal smile, its qualitative and qualitative parameters have not been addressed to sufficiently and are not properly reflected in scientific literature.Purpose. To determine distinguishing features in average smile parameters of the smile in male and female patients with orthognathic occlusion.Materials and methods. A clinical and anthropometric evaluation of parameters in main smile types was carried out for 150 young males and 150 young females aged 19-24 who had identical physiological development parameters.Results. It has been revealed that occurrence frequency of main smile types in patients with orthognathic occlusion has pronounced signs of sexual dimorphism which in over one half of the cases lies in predominance of the incisal smile type in males (52.7%) and the fascial type in females (55.3%). Occurence frequency of the cervical smile type totaled 25% among the studied patients of both genders. Average vertical size parameters in the incisal smile lies within the diapason of 3.91-4.91mm with surpassing by 1mm in males. Analogical data for the fascial smile type form the diapason of 6.21-6.73mm with surpassing by 0.52mm in females. The cervical smile type is characterised by larger vertical size forming the diapason of 7.94-8.91mm with surpassing by 0.97mm in males.Conclusion. The results of the study have shown that the “beautiful and ideal smile” is a relative concept having varied anthropometric characteristics and pronounced signs of sexual dimorphism lying in a broad spectrum of the dentofacial system norm notion with specific vectors for individual morphological deviations.

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