Sex differences in the developmental origins of hypertension and cardiorenal disease

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2008-12, Vol.295 (6), p.R1941-R1952
• Main Authors: Gilbert, Jeffrey S, Nijland, Mark J
• Format: Article
• Language: English
• Subjects: Animals; Birth Weight; Developmental Physiology and Pregnancy; Disease Progression; Epigenesis, Genetic; Female; Food Deprivation; Gender differences; Gene Expression Regulation, Developmental; Gonadal Steroid Hormones - metabolism; Heart Diseases - embryology; Heart Diseases - etiology; Heart Diseases - genetics; Heart Diseases - metabolism; Hormones; Humans; Hypertension; Hypertension - embryology; Hypertension - etiology; Hypertension - genetics; Hypertension - metabolism; Kidney Diseases - embryology; Kidney Diseases - etiology; Kidney Diseases - genetics; Kidney Diseases - metabolism; Kidneys; Maternal Nutritional Physiological Phenomena; Placental Circulation; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Sex Factors; Tissues
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.90724.2008

1 Department of Physiology and Pharmacology, University of Minnesota Medical School Duluth; 2 Duluth Medical Research Institut, Duluth, Minnesota; and 3 The Center for Pregnancy and Newborn Research and the Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas Submitted 26 August 2008 ; accepted in final form 2 October 2008 ABSTRACT 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. placenta; estrogen; maternal nutrient restriction; hypertension Address for reprint requests and other correspondence: J. S Gilbert, Dept. of Physiology and Pharmacology, Univ. of Minnesota Medical School-Duluth, Duluth, MN 55812 (e-mail: jgilbert{at}d.umn.edu )