Sex differences in the developmental origins of hypertension and cardiorenal disease

The “developmental origins of health and disease” (DOHAD) hypothesis derives from clinical observations, indicating long-term health consequences for persons of low birth weight. There is growing evidence, primarily from animal studies, that supports the idea that processes put in motion during development that contribute to DOHAD do not necessarily reflect as significantly compromised growth and altered birth weight. Throughout the body of work investigating the DOHAD hypothesis, several themes have emerged; the importance of the placenta, the presence of critical periods of vulnerability, the involvement of the kidney in programmed hypertension, the presence of sex differences in the progression and development of adult diseases. Despite compelling findings in recent studies, much remains unclear regarding the impact of biological sex in the progression of human diseases, in general, and in the mechanisms underlying developmentally programmed responses, in particular. Although the contribution of biological sex to DOHAD is increasingly recognized, it also appears that it may exert distinctly different influences during fetal and adult life. The mechanisms by which biological sex contributes to these processes remains nebulous at present; nevertheless, several intriguing mechanistic candidates have been proposed ranging from differences in the amounts of sex hormones (e.g., estrogens, androgens) to recently described sexual dimorphism in the transcriptome of a variety of mammalian tissues. Recognizing the influences of biological sex or sex hormones on DOHAD uniquely situates research in this area to provide significant insights into the development and progression of many diseases, recent examples of which are the subject of this review.

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1524. Sex Differences in Influenza: The Challenge Study Experience

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1705 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S764-S764

Author(s):

Luca Giurgea ◽

Adriana Cervantes-Medina ◽

Alison Han ◽

Lindsay Czajkowski ◽

Holly Baus ◽

...

Keyword(s):

Sex Differences ◽

Influenza A ◽

Animal Studies ◽

Influenza Infection ◽

Reproductive Age ◽

Experimental Therapy ◽

Duration Of Symptoms ◽

Biological Sex ◽

Viral Shedding ◽

The Impact

Abstract Background Our understanding of the impact of biological sex on influenza-associated disease and the mechanisms that underpin it is still incomplete. Further investigation of sex-linked effects on influenza pathogenesis and clinical outcomes may help tailor vaccine strategies. Animal studies have shown female mice experience more symptoms than male mice during influenza infection. Similarly, human females of reproductive age have higher rates of influenza and influenza-related hospitalizations. However, data is sometimes conflicting and may be confounded by other important differences in baseline characteristics. Human challenge studies have demonstrated the importance of NAI titers as a correlate of protection and may also provide an ideal opportunity to study sex differences in a homogenous group of participants controlled for confounders. Methods Data from 168 volunteers who underwent Influenza A/California/04/2009/H1N1 challenge studies affiliated with NIAID’s LID Clinical Studies Unit were compiled to compare differences between sexes. Participants were included in the analysis if they received a challenge dose of virus of 107 TCID50 and were excluded if they had received any vaccines or experimental therapy during the study period. Results Baseline differences between male and female participants were observed in NAI titers but not HAI titers or age. Outcomes of interest included presence of viral shedding/duration which were similar among sexes. However, symptom number and duration were higher among female participants (p=0.008 and p=0.045 respectively). Ongoing data analysis also shows females have lower post-challenge NAI titers than males. Conclusion Female participants in our H1N1 challenge studies had more symptoms and a longer duration of symptoms compared to their male counterparts. Differences in NAI titers may potentially explain the observed relationship between sex and symptoms associated with influenza. Disclosures All Authors: No reported disclosures

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Unexplored functions of sex hormones in glioblastoma cancer stem cells

Endocrinology ◽

10.1210/endocr/bqac002 ◽

2022 ◽

Author(s):

Juyeun Lee ◽

Katie Troike ◽

R’ay Fodor ◽

Justin D Lathia

Keyword(s):

Stem Cells ◽

Immune Response ◽

Sex Differences ◽

Cancer Stem Cells ◽

Tumor Growth ◽

Sex Hormones ◽

Cellular Heterogeneity ◽

Cellular Functions ◽

Biological Sex ◽

Organismal Development

Abstract Biological sex impacts a wide array of molecular and cellular functions that impact organismal development and can influence disease trajectory in a variety of pathophysiological states. In non-reproductive cancers, epidemiological sex differences have been observed in a series of tumors, and recent work has identified previously unappreciated sex differences in molecular genetics and immune response. However, the extent of these sex differences in terms of drivers of tumor growth and therapeutic response is less clear. In glioblastoma, the most common primary malignant brain tumor, there is a male bias in incidence and outcome, and key genetic and epigenetic differences, as well as differences in immune response driven by immune-suppressive myeloid populations, have recently been revealed. Glioblastoma is a prototypic tumor in which cellular heterogeneity is driven by populations of therapeutically resistant cancer stem cells (CSCs) that underlie tumor growth and recurrence. There is emerging evidence that GBM CSCs may show a sex difference, with male tumor cells showing enhanced self-renewal, but how sex differences impact CSC function is not clear. In this mini-review, we focus on how sex hormones may impact CSCs in GBM and implications for other cancers with a pronounced CSC population. We also explore opportunities to leverage new models to better understand the contribution of sex hormones versus sex chromosomes to CSC function. With the rising interest in sex differences in cancer, there is an immediate need to understand the extent to which sex differences impact tumor growth, including effects on CSC function.

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An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes?

Prehospital and Disaster Medicine ◽

10.1017/s1049023x20000837 ◽

2020 ◽

Vol 35 (4) ◽

pp. 438-441 ◽

Cited By ~ 10

Author(s):

Parisa Maleki Dana ◽

Fatemeh Sadoughi ◽

Jamal Hallajzadeh ◽

Zatollah Asemi ◽

Mohammad Ali Mansournia ◽

...

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Severe Form ◽

Immune Functions ◽

Angiotensin Converting Enzyme 2 ◽

Underlying Causes ◽

Disaggregated Data ◽

The Impact ◽

Insight Into ◽

Hormonal Levels

AbstractStudies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

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Development of Sexuality in Female Children and Adolescents*

The Canadian Journal of Psychiatry ◽

10.1177/070674378903400907 ◽

1989 ◽

Vol 34 (9) ◽

pp. 879-883 ◽

Cited By ~ 1

Author(s):

Margaret Whitfield

Keyword(s):

Sex Differences ◽

Children And Adolescents ◽

Sexual Desire ◽

Female Sexuality ◽

The Body ◽

Childhood And Adolescence ◽

The Past ◽

Female Children ◽

Women's Lives ◽

The Impact

Female sexuality (meaning sexual desire, excitement and orgasm) has been of considerable interest in psychiatry. Women's efforts to define and legitimize their own experience of their sexuality have increased in the past 25 years. However, the integration of these new views into the body of psychiatric (especially psychoanalytic) theory has not occurred very actively or successfully. Very little is known about the development of sexuality in childhood and adolescence. This paper looks at various behaviours, interests and events in women's lives that might reveal something about the development of their sexuality. The literature on female masturbation is reviewed and some sex differences highlighted. The literature on interest in babies, the wish to have babies, and menarche is explored for possible associations with sexuality. Rather than sexuality being a central organizer of experience, it seems quite possible that experience is an organizer of sexuality. Therefore, to better understand female sexuality we need to consider the impact of experiences during childhood and adolescence.

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Probing the Impact of Gender-Affirming Hormone Treatment on Odor Perception

Chemical Senses ◽

10.1093/chemse/bjz069 ◽

2019 ◽

Vol 45 (1) ◽

pp. 37-44 ◽

Cited By ~ 2

Author(s):

Georg S Kranz ◽

Ulrike Kaufmann ◽

Rupert Lanzenberger

Keyword(s):

Sex Hormones ◽

Hormone Treatment ◽

Sex Hormone ◽

Test Battery ◽

Sex Hormone Binding Globulin ◽

Odor Perception ◽

Biological Sex ◽

Transgender Persons ◽

Significant Difference ◽

The Impact

Abstract Evidence suggests that women outperform men in core aspects of odor perception, and sex hormones may play a significant role in moderating this effect. The gender-affirming treatment (GAT) of transgender persons constitutes a powerful natural experiment to study the psychological and behavioral effects of high dosages of cross-sex hormone applications. Therefore, our aim was to investigate the effects of GAT on odor perception in a sample of 131 participants including female and male controls, as well as transmen and transwomen over their first 4 months of gender transition. The Sniffin’ Sticks test battery was used to measure odor detection, discrimination, and identification at baseline, as well as 1 and 4 months after the start of GAT. Plasma levels of estradiol, testosterone, and sex hormone-binding globulin were analyzed for each assessment point. Results revealed no significant change of olfactory performance in the two transgender groups compared with female and male controls. There was no significant difference between groups at baseline or any other time point. Neither biological sex, nor gender identity had an influence on odor perception. Moreover, there was no significant correlation between sex hormones and odor perception and between GAT-induced changes in sex hormones and changes in odor perception. Our results indicate that the effects of sex hormones on olfactory performance are subtle, if present at all. However, our results do not preclude hormonal effects on odors not included in the Sniffin’ Sticks test battery, such as body odors or odors associated with sex.

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Epigenetics and developmental origins of diabetes: correlation or causation?

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00424.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. E15-E28 ◽

Cited By ~ 18

Author(s):

Amita Bansal ◽

Rebecca A. Simmons

Keyword(s):

Animal Studies ◽

Metabolic Diseases ◽

Epigenetic Modification ◽

Developmental Origins ◽

Critical Periods ◽

Metabolic Outcome ◽

Health And Disease ◽

Founding Principle ◽

The Many

The incidence of metabolic disorders like type 2 diabetes (T2D) and obesity continue to increase. Although it is evident that the increasing incidence of diabetes confers a global societal and economic burden, the mechanisms responsible for the increased incidence of T2D are not well understood. Extensive efforts to understand the association of early-life perturbations with later onset of metabolic diseases, the founding principle of developmental origins of health and disease, have been crucial in determining the mechanisms that may be driving the pathogenesis of T2D. As the programming of the epigenome occurs during critical periods of development, it has emerged as a potential molecular mechanism that could occur early in life and impact metabolic health decades later. In this review, we critically evaluate human and animal studies that illustrated an association of epigenetic processes with development of T2D as well as intervention strategies that have been employed to reverse the perturbed epigenetic modification or reprogram the naturally occurring epigenetic marks to favor improved metabolic outcome. We highlight that although our understanding of epigenetics and its contribution toward developmental origins of T2D continues to grow, whether epigenetics is a cause, consequence, or merely a correlation remains debatable due to the many limitations/challenges of the existing epigenetic studies. Finally, we discuss the potential of establishing collaborative research efforts between different disciplines, including physiology, epigenetics, and bioinformatics, to help advance the developmental origins field with great potential for understanding the pathogenesis of T2D and developing preventive strategies for T2D.

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Sex Differences in Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.141 ◽

2012 ◽

Vol 32 (12) ◽

pp. 2100-2107 ◽

Cited By ~ 113

Author(s):

Roy AM Haast ◽

Deborah R Gustafson ◽

Amanda J Kiliaan

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Premenopausal Women ◽

Epidemiologic Studies ◽

Stroke Onset ◽

Effective Prevention ◽

Sex Steroid Hormone ◽

Incidence And Mortality ◽

Primary Focus ◽

The Impact

Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment.

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Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

Frontiers in Endocrinology ◽

10.3389/fendo.2021.652444 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kasiphak Kaikaew ◽

Aldo Grefhorst ◽

Jenny A. Visser

Keyword(s):

Sex Differences ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Sex Hormones ◽

Energy Homeostasis ◽

Overweight And Obesity ◽

The Body ◽

Bat Activity ◽

Pathological Conditions ◽

Brown Adipose

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.

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The Impact of Maternal Preeclampsia and Hyperglycemia on the Cardiovascular Health of the Offspring: A Systematic Review and Meta-Analysis

American Journal of Perinatology ◽

10.1055/s-0041-1728823 ◽

2021 ◽

Author(s):

Zahra Hoodbhoy ◽

Nuruddin Mohammed ◽

Karim Rizwan Nathani ◽

Saima Sattar ◽

Devyani Chowdhury ◽

...

Keyword(s):

Systematic Review ◽

Body Composition ◽

Birth Weight ◽

Vascular Function ◽

Cardiovascular Health ◽

Meta Analysis ◽

The Body ◽

Cochrane Library ◽

And Function ◽

The Impact

Objectives The objective of this review was to assess the impact of maternal preeclampsia or hyperglycemia on the body composition and cardiovascular health in the offspring. Study Design We conducted a systematic review utilizing PubMed, EBSCO, CINAHLPlus, Cochrane Library, and Web of Science to include all studies assessing the impact of preeclampsia/eclampsia and/or gestational/pregestational diabetes mellitus on the health of the offspring (children <10 years of age). The health measures included anthropometry, cardiac dimensions and function, and vascular function. We performed a meta-analysis using Review Manager software and computed net risk ratio (RR) with 95% confidence interval (CI) for dichotomous data and mean difference (MD) with 95% CI for continuous data. Results There were 6,376 studies in total, of which 45 were included in the review and 40 in the meta-analysis. The results demonstrated higher birth weight (MD: 0.12 kg; 95% CI: 0.06–0.18) and systolic and diastolic blood pressure (BP; MD: 5.98 mmHg; 95% CI: 5.64–6.32 and MD: 3.27 mmHg; 95% CI: 0.65–5.89, respectively) in the offspring of mothers with gestational diabetes compared to controls. In contrast, the offspring of mothers with preeclampsia had lower birth weight (MD: −0.41 kg; 95% CI: −0.7 to −0.11); however, they had increased systolic (MD: 2.2 mmHg; 95% CI: 1.28–3.12) and diastolic BP (MD: 1.41 mmHg; 95% CI: 0.3–2.52) compared to controls. There is lack of data to conduct a meta-analysis of cardiac morphology, functional, and vascular imaging parameters. Conclusion These findings suggest that the in-utero milieu can have a permanent impact on the body composition and vascular health of the offspring. Future work warrants multicenter prospective studies to understand the mechanism and the actual effect of exposure to maternal hyperglycemia and high BP on the cardiovascular health of the offspring and long-term outcomes. Key Points

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