Inclusion of females does not increase variability in rodent research studies

Beery, Annaliese K.

doi:10.1016/j.cobeha.2018.06.016

Cited by 281 publications

(229 citation statements)

References 46 publications

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“…Other female offspring were assessed for distinct behavioural phenotypes in adulthood for a separate study. We did not assess oestrous cycle during these tasks; however, previous work has shown that variability across the cycle is not sufficiently substantial to change the interpretability of several phenotypes . The testing occurred over two cohorts: the first cohort included one to two pups from 20 litters and the second cohort included five to six pups from four litters.…”

Section: Methodsmentioning

confidence: 99%

“…We did not assess oestrous cycle during these tasks; however, previous work has shown that variability across the cycle is not sufficiently substantial to change the interpretability of several phenotypes. 36 The testing occurred over two cohorts: the first cohort included one to two pups from 20 litters and the second cohort included five to six pups from four litters. There were no significant differences between cohorts in total litter size or any of the behaviour measures (all P > 0.10) and were therefore analysed together.…”

Section: Dopamine-related Behaviour Tasksmentioning

confidence: 99%

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Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

Lauby

Chatterjee

Pan

et al. 2019

J Neuroendocrinology

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Rat mothers exhibit natural variations in care and can shape offspring adult behaviour and their maternal care by affecting the dopaminergic system. We explored whether genotype and gene × environment interactions are involved in these processes in nulliparous female offspring. We assessed maternal licking/grooming toward individual female pups during the first week postpartum and dopamine‐related behaviour of the offspring in adulthood. Behaviours explored included strategy shifting, impulsive action and sucrose preference. Single nucleotide polymorphisms in the dopamine receptor 2, dopamine transporter and catechol‐O‐methyltransferase genes were examined in relation to offspring behaviour and baseline dopamine turnover in select brain regions. Dopamine receptor 2 (RS107017253) variation moderated, or interacted with, the relationship between early‐life licking received and behaviour. Specifically, offspring with the A/A genotype showed a significant correlation between early‐life licking received and behaviour. Offspring with the A/G and G/G genotypes did not show this relationship. Dopamine transporter gene variation affected offspring behaviour regardless of early‐life licking received. Our findings suggest that genotype can directly affect dopamine‐related behaviours and alter the sensitivity of offspring to the maternal environment. This could be informative on how maternal care is transmitted between generations of female offspring.

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Section: Methodsmentioning

confidence: 99%

Section: Dopamine-related Behaviour Tasksmentioning

confidence: 99%

Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

Lauby

Chatterjee

Pan

et al. 2019

J Neuroendocrinology

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“…We can hypothesize that the reasons contributing to the bias in preclinical research [64][65][66][67] are also, at least partially, the same for human studies as well. For instance, the misconception about the increased female 66,68,69 variability-often argued because of the fluctuating sex 64 hormones-and the misguided assumption that the biological sex does not influence the function of the central nervous system are among them, especially in the fields of neuroscience and psychiatry. 65 In addition, human brain samples are difficult samples to collect in big numbers, 53 especially from psychiatric patients.…”

Section: Human Studiesmentioning

confidence: 99%

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Brivio

López

Chen

2020

Genes Brain and Behavior

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More than two‐thirds of patients suffering from stress‐related disorders are women but over two‐thirds of suicide completers are men. These are just some examples of the many sex differences in the prevalence and manifestations of stress‐related disorders, such as major depressive disorder, post‐traumatic stress disorder, and anxiety disorders, which have been extensively documented in clinical research. Nonetheless, the molecular origins of this sex dimorphism are still quite obscure. In response to this lack of knowledge, the NIH recently advocated implementing sex as biological variable in the design of preclinical studies across disciplines. As a result, a newly emerging field within psychiatry is trying to elucidate the molecular causes underlying the clinically described sex dimorphism. Several studies in rodents and humans have already identified many stress‐related genes that are regulated by acute and chronic stress in a sex‐specific fashion. Furthermore, current transcriptomic studies have shown that pathways and networks in male and female individuals are not equally affected by stress exposure. In this review, we give an overview of transcriptional studies designed to understand how sex influences stress‐specific transcriptomic changes in rodent models, as well as human psychiatric patients, highlighting the use of different methodological techniques. Understanding which mechanisms are more affected in males, and which in females, may lead to the identification of sex‐specific mechanisms, their selective contribution to stress susceptibility, and their role in the development of stress‐related psychiatric disorders.

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“…There was no correlation with estrus cycle phase and behavioral performance, demonstrating that hormonal fluctuations throughout the cycle did not affect the cognitive outcomes measured here. In line with these data, there are several reports demonstrating that there is commonly no requirement for increasing sample size to incorporate females and furthermore no need to account for estrus cycle phase unless that is the focus of the study [39][40][41][42].…”

Section: Discussionmentioning

confidence: 83%

Sex Differences in Age-related Impairments Vary across Cognitive and Physical Assessments in Rats

Hernandez

Truckenbrod

Campos

et al. 2019

Preprint

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Inclusion of female subjects in biomedical research is imperative for understanding the mechanisms of age-related cognitive decline, as more than half of individuals older than 65 are female. Few behavioral and physical assays, however, have been conducted in both sexes within the same study. In the current experiments young and aged male and female rats underwent a battery of cognitive and physical assessments to examine for potential sex and age differences. Physical performance was measured with a rotarod test of motor coordination, assessment of maximum grip strength and swim speed. While there were differences between males and females in rotarod and grip strength, there was also a clear age-dependent decline in physical performance in both sexes. Cognitive assessment included the Morris watermaze test of hippocampal dependent spatial navigation and a biconditional association task (BAT) with a working memory (WM) component. Notably, a similar BAT has previously been validated as a more sensitive assay of age-related cognitive decline than the watermaze in male rats, which is replicated here in both female and male rats. Furthermore, young and aged female rats both spent a similar percent of time in each estrus cycle phase and phase did not influence WM/BAT performance. In conclusion, robust age differences in biconditional association task performance are observed in both sexes with no need for increased cohort size. Thus, future studies utilizing similar behavioral paradigms should be representative of the human population they intend to model through the inclusion of female subjects.

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Inclusion of females does not increase variability in rodent research studies

Cited by 281 publications

References 46 publications

Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Sex Differences in Age-related Impairments Vary across Cognitive and Physical Assessments in Rats

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