Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health.

The global incidence of obesity continues to rise, which increases the prevalence of metabolic diseases. We previously demonstrated the beneficial effect of adipose-specific growth hormone receptor (Ghr) knockout (KO) on metabolic parameters in male mice exposed to high fat diet. Although the effect of the growth hormone (GH) axis on lipid metabolism has been well studied, sexual dimorphism has not been considered. Furthermore, the effects of the GH axis on intergenerational adipose development are understudied. The present study aimed to evaluate whether adipose-specific Ghr knockout is associated with sex-specific differences in metabolic health of female offspring. Ghrflox/flox (LL) mice were crossed with Adipoq-Cre mice to generate adipose-specific Ghr knockout (KO) mice. Physiological phenotype and fertility of female LL and KO mice were measured. Body weight, organ weight, glucose homeostasis, liver and adipose histology, hepatic triglycerides (TG) content, serum TG and low-density lipoprotein cholesterol (LDL-C) levels of female offspring were detected. We found an increase in adipocyte size in female KO mice, but no change in glucose tolerance or insulin sensitivity. Adipose-specific Ghr deficiency impairs fertility in female KO mice. Maternal adipose-specific Ghr deficiency had a considerable beneficial effect on glucose metabolism in female offspring. The female offspring of the KO mice were protected against diet-induced obesity and the degree of hepatic steatosis and hyperlipidemia was reduced. The adipocyte size of the KO offspring did not change significantly despite the decrease in fat weight. Furthermore, the phenotypes of the offspring of LL mice fostered by the KO mothers differed from those of offspring remaining in the maternal nest. The findings of our study suggest that adipose GH axis plays a complex and important role in the intergenerational effects of metabolic health and adipocytes on offspring in a sex-specific manner. Future studies are needed to reveal the mechanisms of these sexually dimorphic phenotypes and the feasibility of providing new interventions for improving offspring metabolic health.

被引量：- 发表：1970

Application and insights of targeted next-generation sequencing in a large cohort of 46,XY disorders of sex development in Chinese.

被引量：- 发表：1970

Histological observations and transcriptome analyses reveal the dynamic changes in the gonads of the blotched snakehead (Channa maculata) during sex differentiation and gametogenesis.

Blotched snakehead (Channa maculata) displays significant sexual dimorphism, with males exhibiting faster growth rates and larger body sizes compared to females. The cultivation of the all-male population of snakeheads holds substantial economic and ecological value. Nonetheless, the intricate processes governing the development of bipotential gonads into either testis or ovary in C. maculata remain inadequately elucidated. Therefore, it is necessary to determine the critical time window of sex differentiation in C. maculata, providing a theoretical basis for sex control in production practices. The body length and weight of male and female C. maculata were measured at different developmental stages to reveal when sexual dimorphism in growth initially appears. Histological observations and spatiotemporal comparative transcriptome analyses were performed on ovaries and testes across various developmental stages to determine the crucial time windows for sex differentiation in each sex and the sex-related genes. Additionally, qPCR and MG2C were utilized to validate and locate sex-related genes, and levels of E2 and T were quantified to understand sex steroid synthesis. Sexual dimorphism in growth became evident starting from 90 dpf. Histological observations revealed that morphological sex differentiation in females and males occurred between 20 and 25 dpf or earlier and 30-35 dpf or earlier, respectively, corresponding to the appearance of the ovarian cavity or efferent duct anlage. Transcriptome analyses revealed divergent gene expression patterns in testes and ovaries after 30 dpf. The periods of 40-60 dpf and 60-90 dpf marked the initiation of molecular sex differentiation in females and males, respectively. Male-biased genes (Sox11a, Dmrt1, Amh, Amhr2, Gsdf, Ar, Cyp17a2) likely play crucial roles in male sex differentiation and spermatogenesis, while female-biased genes (Foxl2, Cyp19a1a, Bmp15, Figla, Er) could be pivotal in ovarian differentiation and development. Numerous biological pathways linked to sex differentiation and gametogenesis were also identified. Additionally, E2 and T exhibited sexual dimorphism during sex differentiation and gonadal development. Based on these results, it is hypothesized that in C. maculata, the potential male sex differentiation pathway, Sox11a-Dmrt1-Sox9b, activates downstream sex-related genes (Amh, Amhr2, Gsdf, Ar, Cyp17a2) for testicular development, while the antagonistic pathway, Foxl2/Cyp19a1a, activates downstream sex-related genes (Bmp15, Figla, Er) for ovarian development. This study provides a comprehensive overview of gonadal dynamic changes during sex differentiation and gametogenesis in C. maculata, establishing a scientific foundation for sex control in this species.

被引量：- 发表：1970

Sex-specific associations of Notch signaling with chronic HBV infection: a study from Taiwan Biobank.

Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.

被引量：- 发表：1970

Sex-specific cardiac remodeling in aged rats after adolescent chronic stress: associations with endocrine and metabolic factors.

Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early-life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner. Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43-62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups. Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased concentric VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity. These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for assessing cardiovascular risk based on biological sex and prior adverse experiences.

被引量：- 发表：1970