Dataset Information

Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats.

ABSTRACT: Despite the striking differences between male and female physiology, female physiology is understudied. In response, the National Institutes of Health is promulgating new policies to increase the use of female organisms in preclinical research. Females are commonly believed to have greater variability than males because of the estrous cycle, but recent studies call this belief into question. Effects of estrous cycling on mean arterial pressure were assessed in female Dahl S rats using telemetry and vaginal cytometry and found that estrous cycling did not affect mean arterial pressure magnitude or variance. Data from the PhysGen arm of the Program for Genomic Applications was used to compare male and female variance and coefficient of variation in 142 heart, lung, vascular, kidney, and blood phenotypes, each measured in hundreds to thousands of individual rats from over 50 inbred strains. Seventy-four of 142 phenotypes from this data set demonstrated a sex difference in variance; however, 59% of these phenotypes exhibited greater variance in male rats rather than female. Remarkably, a retrospective power analysis demonstrated that only 16 of 74 differentially variable phenotypes would be detected when using an experimental cohort large enough to detect a difference in magnitude. No overall difference in coefficient of variation between male and female rats was detected when analyzing these 142 phenotypes. We conclude that variability of 142 traits in male and female rats is similar, suggesting that differential treatment of males and females for the purposes of experimental design is unnecessary until proven otherwise, rather than the other way around.

SUBMITTER: Dayton A

PROVIDER: S-EPMC5104284 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats.

Dayton Alex A Exner Eric C EC Bukowy John D JD Stodola Timothy J TJ Kurth Theresa T Skelton Meredith M Greene Andrew S AS Cowley Allen W AW

Hypertension (Dallas, Tex. : 1979) 20160926 5

Despite the striking differences between male and female physiology, female physiology is understudied. In response, the National Institutes of Health is promulgating new policies to increase the use of female organisms in preclinical research. Females are commonly believed to have greater variability than males because of the estrous cycle, but recent studies call this belief into question. Effects of estrous cycling on mean arterial pressure were assessed in female Dahl S rats using telemetry ...[more]

PMID: 27672030

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Project description:Brain structure and function are sexually dimorphic. As neuroscience research has largely focused on the male brain and behavior, the female brain and, in particular, its inherent dynamics have been left underexplored. During the mammalian reproductive period, the female brain is exposed to fluctuating hormone levels over the cycles known as menstrual (in humans) or estrous (in rodents). Variation in estradiol levels has been shown to affect synaptic plasticity in the female brain, including changes in dendritic spine density systematically across the estrous cycle. Female emotionality and cognitive function vary with physiologically fluctuating sex hormone levels. However, the molecular mechanisms underlying the dynamic nature of the female brain structure and function are currently unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse is dynamic and fluctuates across the estrous cycle. We find changes in chromatin organization associated with the transcriptional activity of nearby genes important for neuronal function, neurotransmission, synapse formation, and behavior. We also link these chromatin dynamics to variation in anxiety-like behavior and to fluctuations in dendritic spine and synaptic density in the ventral hippocampus. In terms of chromatin structure, within-female and between-sex variation are of similar magnitudes, emphasizing the importance of accounting for fluctuating sex-hormone levels in females in the studies of the brain epigenome and behavior. These results provide critical insights into the mechanisms underlying sex-hormone and sex-dependent variation in adult brain structure and function. The study also has implications for better understanding of sex-biased disorders such as depression and anxiety which are strongly associated with sex-hormone status in females and are twice as prevalent in women than in men. This study establishes a foundation for the development of sex-specific approaches to treat sex-biased neuropsychiatric disorders including depression and anxiety disorders.

Dataset Information

Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats.

Publications

Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats.

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