Developmental mechanisms of sex differences: from cells to organisms

Development ◽  
2021 ◽  
Vol 148 (19) ◽  
Author(s):  
Judith E. Mank ◽  
Elizabeth J. Rideout

ABSTRACT Male-female differences in many developmental mechanisms lead to the formation of two morphologically and physiologically distinct sexes. Although this is expected for traits with prominent differences between the sexes, such as the gonads, sex-specific processes also contribute to traits without obvious male-female differences, such as the intestine. Here, we review sex differences in developmental mechanisms that operate at several levels of biological complexity – molecular, cellular, organ and organismal – and discuss how these differences influence organ formation, function and whole-body physiology. Together, the examples we highlight show that one simple way to gain a more accurate and comprehensive understanding of animal development is to include both sexes.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yide Yang ◽  
Ming Xie ◽  
Shuqian Yuan ◽  
Yuan Zeng ◽  
Yanhui Dong ◽  
...  

Abstract Background We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. Methods A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. Results In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12–0.35 and OR: 0.22, 95%CI: 0.12–0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02–3.55), 2.91 (95%CI: 1.75–4.85), and 2.01 (95%CI: 1.47–2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02–0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05–0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42–8.09 and OR: 2.45, 95%CI: 1.53–3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42–3.19). Conclusions Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.


2015 ◽  
Vol 41 (2) ◽  
pp. 540-545 ◽  
Author(s):  
Dustin A. Bruening ◽  
Rebecca E. Frimenko ◽  
Chuck D. Goodyear ◽  
David R. Bowden ◽  
Adam M. Fullenkamp

2014 ◽  
Vol 39 (7) ◽  
pp. 843-843
Author(s):  
Daniel Gagnon

The current thesis examined whether sex differences in local and whole-body heat loss are evident after accounting for confounding differences in physical characteristics and rate of metabolic heat production. Three experimental studies were performed: the first examined whole-body heat loss in males and females matched for body mass and surface area during exercise at a fixed rate of metabolic heat production; the second examined local and whole-body heat loss responses between sexes during exercise at increasing requirements for heat loss; the third examined sex-differences in local sweating and cutaneous vasodilation to given doses of pharmacological agonists, as well as during passive heating. The first study demonstrated that females exhibit a lower whole-body sudomotor thermosensitivity (553 ± 77 vs. 795 ± 85 W·°C−1, p = 0.05) during exercise performed at a fixed rate of metabolic heat production. The second study showed that whole-body sudomotor thermosensitivity is similar between sexes at a requirement for heat loss of 250 W·m−2 (496 ± 139 vs. 483 ± 185 W·m−2·°C−1, p = 0.91) and 300 W·m−2 (283 ± 70 vs. 211 ± 66 W·m−2·°C−1, p = 0.17), only becoming greater in males at a requirement for heat loss of 350 W·m−2 (197 ± 61 vs. 82 ± 27 W·m−2·°C−1, p = 0.007). In the third study, a lower sweat rate to the highest concentration of acetylcholine (0.27 ± 0.08 vs. 0.48 ± 0.13 mg·min−1·cm−2, p = 0.02) and methacholine (0.41 ± 0.09 vs. 0.57 ± 0.11 mg·min−1·cm−2, p = 0.04) employed was evidenced in females, with no differences in cholinergic sensitivity. Taken together, the results of the current thesis show that sex itself can modulate sudomotor activity, specifically the thermosensitivity of the response, during both exercise and passive heat stress. Furthermore, the results of the third study point towards a peripheral modulation of the sweat gland as a mechanism responsible for the lower sudomotor thermosensitivity in females.


2018 ◽  
Vol 59 (10) ◽  
pp. 1203-1209 ◽  
Author(s):  
Corey M Gill ◽  
Debora C Azevedo ◽  
Adriana L Oliveira ◽  
Edgar L Martinez-Salazar ◽  
Martin Torriani ◽  
...  

Background Recent studies suggest that pericardial adipose tissue (PAT) is associated with whole body adiposity and insulin resistance. Moreover, the incidence of cardiovascular disease (CVD) differs between men and women. Although CVD is more prevalent in men, women suffering from CVD have a higher mortality compared to men. Differences in PAT may account for some of the observed sex differences in manifestations of CVD. Purpose To assess pericardial adipose tissue (PAT) as a biomarker for cardiometabolic risk and to assess potential sex differences. Material and Methods We studied 303 individuals (151 women, 152 men; mean age = 57 ± 17 years) across the weight spectrum. PAT and abdominal adipose tissue were quantified using clinical computed tomography (CT) scans obtained as part of a positron emission tomography (PET)/CT. Cardiometabolic risk factors were assessed from medical records. Linear regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate associations between PAT and cardiometabolic risk. Results PAT was higher in overweight and obese individuals compared to lean individuals and higher in men compared to women. PAT was positively associated with body mass index, abdominal fat ( P < 0.0001), fasting glucose, and serum lipids ( P < 0.05) with stronger associations in women than in men. PAT was accurate in detecting the prevalence of the metabolic syndrome with 74% sensitivity and 76% specificity (AUC = 0.80). Conclusion PAT is associated with measures of cardiometabolic risk and these associations are stronger in women compared to men. PAT could serve as a biomarker for opportunistic screening for cardiometabolic risk in patients undergoing chest CT.


2017 ◽  
Vol 372 (1729) ◽  
pp. 20160310 ◽  
Author(s):  
Tim Clutton-Brock

This paper traces the development of our understanding of the development of different approaches to estimating the strength of reproductive competition and sexual selection in the two sexes, based on measures of the operational sex ratio, the opportunity for sexual selection and contrasts in selection gradients between the sexes. It argues that different approaches provide complementary insights into the causes of sex differences in reproductive competition, the operation of sexual selection and the evolution of secondary sexual characters and that improvements in our understanding of the evolution of secondary sexual characters will require a more comprehensive understanding of the ways in which social and ecological conditions modify reproductive competition and development in females and males. This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.


2020 ◽  
Author(s):  
Robin J.G. Hartman ◽  
Michal Mokry ◽  
Gerard Pasterkamp ◽  
Hester M. den Ruijter

AbstractMany pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene activity map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 20.1% of the gene activity is influenced by sex. For example, skeletal muscle was predominantly enriched with genes more active in males, whereas thyroid primarily contained genes more active in females. This was accompanied by consistent sex differences in pathway activity, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene activity over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are known druggable targets. This emphasizes sex as a biological variable and the need to incorporate sex in systems biology studies.


2007 ◽  
Vol 292 (1) ◽  
pp. E77-E83 ◽  
Author(s):  
Satoshi Fujita ◽  
Blake B. Rasmussen ◽  
Jill A. Bell ◽  
Jerson G. Cadenas ◽  
Elena Volpi

Sexual dimorphism in skeletal muscle mass is apparent, with men having more muscle mass and larger individual muscle cells. However, no sex-based differences have been detected in blood forearm phenylalanine turnover, although whole body leucine oxidation has been reported to be greater in men than in women. We hypothesized that sex differences in intracellular amino acid turnover may account for these discrepancies, with men having a higher intracellular turnover than women. We studied young, healthy women (women, n = 8) and men (men, n = 10) following an overnight fast. Phenylalanine, leucine, and alanine muscle intracellular kinetics were assessed using stable isotope methodologies, femoral arteriovenous blood sampling, and muscle biopsies. Muscle intracellular amino acid kinetics were reported relative to both leg volume and lean leg mass because of sex differences in leg volume and in muscle and fat distribution. When expressed per leg volume (nmol·min−1·100 ml leg volume−1), phenylalanine net balance (women: −16 ± 4, men: −31 ± 5), release from proteolysis in the blood (women: 46 ± 9, men: 75 ± 10) and intracellular availability (women: 149 ± 23, men: 241 ± 35), and alanine production, utilization, and intracellular availability were higher in men ( P < 0.05). However, when the kinetic parameters were normalized per unit of lean leg mass, all differences disappeared. Muscle fractional synthetic rate was also not different between women and men. We conclude that there are no sex-based differences in basal muscle intracellular amino acid turnover when the data are normalized by lean mass. It remains to be determined if there are sex differences in intracellular amino acid metabolism following anabolic or catabolic stimuli.


PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237449
Author(s):  
Dustin A. Bruening ◽  
Andrew R. Baird ◽  
Kelsey J. Weaver ◽  
Austin T. Rasmussen

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