The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1

Duclot, Florian; Kabbaj, Mohamed

doi:10.1186/s13059-015-0815-x

Cited by 62 publications

(47 citation statements)

References 102 publications

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“…However, in other brain regions, the effect of the oestrous cycle can surpass sex differences. For example, Duclot and Kabbaj 52 have shown that the oestrous cycle surpasses sex differences in regulating the transcriptome of the rat medial prefrontal cortex. While hormonal replacement would elucidate whether oestrous cycle surpasses sex differences, or vice-versa, such an approach would entail stressful survival surgery and the stress of hormone treatment.…”

Section: Discussionmentioning

confidence: 99%

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

et al. 2017

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Males and females use distinct brain circuits to cope with similar challenges. Using RNA sequencing of ribosome-bound mRNA from hippocampal CA3 neurons, we found remarkable sex differences and discovered that female mice displayed greater gene expression activation after acute stress than males. Stress-sensitive BDNF Val66Met mice of both sexes show a pre-stressed translational phenotype in which the same genes that are activated without applied stress are also induced in wild-type mice by an acute stressor. Behaviourally, only heterozygous BDNF Val66Met females exhibit spatial memory impairment, regardless of acute stress. Interestingly, this effect is not observed in ovariectomized heterozygous BDNF Val66Met females, suggesting that circulating ovarian hormones induce cognitive impairment in Met carriers. Cognitive deficits are not observed in males of either genotype. Thus, in a brain region not normally associated with sex differences, this work sheds light on ways that genes, environment and sex interact to affect the transcriptome’s response to a stressor.

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Section: Discussionmentioning

confidence: 99%

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

et al. 2017

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“…Therefore, the physiological variations of hormone levels occurring during the cycle represent a powerful tool to study the effects of sex hormones in many organs (i.e., the lung). By investigating females in a state of high or low levels of ovarian hormones related to the estrous cycle, researchers have demonstrated the existence of estrous cycle‐specific sex differences in tissues such as the brain and lung (Duclot and Kabbaj ; Fuentes et al. ; Fuentes and Silveyra ).…”

Section: Introductionmentioning

confidence: 99%

Modulation of the lung inflammatory response to ozone by the estrous cycle

et al. 2019

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Emerging evidence suggests that sex differences exist in the control of lung innate immunity; however, the specific roles of sex hormones in the inflammatory response, and the mechanisms involved are unclear. Here, we investigated whether fluctuations in circulating hormone levels occurring in the mouse estrous cycle could affect the inflammatory response to air pollution exposure. For this, we exposed female mice (C57 BL /6J, 8 weeks old) at different phases of the estrous cycle to 2 ppm of ozone or filtered air ( FA ) for 3 h. Following exposure, we collected lung tissue and bronchoalveolar lavage fluid ( BAL ), and performed lung function measurements to evaluate inflammatory responses and respiratory mechanics. We found a differential inflammatory response to ozone in females exposed in the luteal phase (metestrus, diestrus) versus the follicular phase (proestrus, estrus). Females exposed to ozone in the follicular phase had significantly higher expression of inflammatory genes, including Ccl2, Cxcl2, Ccl20, and Il6, compared to females exposed in the luteal phase ( P < 0.05), and displayed differential activation of regulatory pathways. Exposure to ozone in the follicular phase also resulted in higher BAL neutrophilia, lipocalin levels, and airway resistance than exposure in the luteal phase ( P < 0.05). Together, these results show that the effects of ozone exposure in the female lung are affected by the estrous cycle phase, and potentially hormonal status. Future studies investigating air pollution effects and inflammation in women should consider the menstrual cycle phase and/or circulating hormone levels.

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“…For example, E2-induced Egr3 and Egr4 in OVX WT mice but not in OVX Het-Met mice. Members of the Egr family are involved in brain plasticity and neuropsychiatric disorders related to sex hormones [32,33]. Thus, it is likely that E2-related behavioral impairment is associated with a lack of plasticity in Het-Met mice in response to E2.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back

et al. 2018

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Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17β-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their matched wild-type (WT) mice were administered estradiol or vehicle in drinking water for 6 weeks. Using the open field and the splash test, we show that E2 add-back induces anxiety-like and depression-like behavior in Het-Met mice, but not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that E2-dependent gene expression is markedly different between WT mice and Het-Met mice. Through a comparative whole-genome RNAseq analysis between mouse vHpc and lymphoblastoid cell line cultures from control women and women with PMDD, we discovered common epigenetic biomarkers that transcend species and cell types. Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of response to ovarian steroids. Although the BDNF Met genotype intersects the behavioral and transcriptional traits of women with PMDD, we suggest that these similarities speak to the epigenetic factors by which ovarian steroids produce negative behavioral effects.

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The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1

Cited by 62 publications

References 102 publications

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice

Modulation of the lung inflammatory response to ozone by the estrous cycle

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back

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