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Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.

ABSTRACT: In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week-old mice that had been treated with progesterone or vehicle containing implants from 8 to 36 weeks. Transcript profiling was carried out using Affymetrix Gene ST 1.1 arrays, and data were normalized. We identified 60 differentially regulated transcripts associated with advancing age (group 1). We validated these changes in group 2 (P for overlap = 5.8 × 10(-46) ). Early ovariectomy prevented the age-related changes in myometrial transcript profile. Similarly, progesterone-mediated long-term ovarian suppression prevented the age-related changes in myometrial transcript profile. Interferon regulatory factor 7 (Irf7) mRNA was regulated by age and hormonal exposure, and was identified as a predicted regulator of the other differentially expressed transcripts by both promoter sequence and canonical pathway activation analysis (P = 8.47 × 10(-5) and P < 10(-10) , respectively). Immunohistochemistry demonstrated IRF7 in both mouse and human myometrium. We conclude the following: (i) Myometrial aging in mice is associated with reproducible changes in transcript profile; (ii) these changes can be prevented by interventions which inhibit cyclical changes in the female sex hormones; and (iii) IRF7 may be an important regulator of myometrial function and aging.

SUBMITTER: Chong HP

PROVIDER: S-EPMC4717263 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.

Chong Hsu P HP Cordeaux Yolande Y Ranjan Yorain Sri YS Richardson Sylvia S Liquet Benoit B Smith Gordon C S GC Charnock-Jones David Stephen DS

Aging cell 20151021 1

In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week- ...[more]

PMID: 26490259

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Project description:AimsFirst, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work.Methods for the systematic reviewPopulation, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).ResultsSex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause.ConclusionThe review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.

Project description:In female rodents, sexual receptivity is coordinated with cyclic changes in the release of gonadal hormones. Increases in estradiol (E) and progesterone (P) during proestrus and estrus not only induce ovulation but also modulate behaviors that increase the likelihood that the female will find a mate and reproduce. This includes changes in receptive behaviors, such as lordosis, as well as changes in appetitive or proceptive behaviors, including motivation. Interestingly, the direction of these changes in motivation is dependent on the type of reward that is being pursued. While induction of sexual receptivity by E and P increases motivation for access to a male, motivation for a palatable food reward is decreased. These concurrent changes may facilitate adaptive choice across the estrous cycle; females bias their choice for sex when fertilization is most likely to occur, but for food when copulation is unlikely to result in impregnation. In order to test this hypothesis, we developed a novel paradigm to measure the motivated choice between a palatable food reward and access to a male conspecific. Ovariectomized, hormone primed females were trained to operantly respond for both food and sex on a fixed interval (FI) schedule. After training, unprimed and primed females were tested in a chamber that allows them to choose between food and sex while still requiring responding on the FI schedule for reach reward. From this we can not only determine the impact of hormone priming on female choice for food or sex, but also how this is reflected by changes in motivation for each specific reward, as measured by the average number of responses made during each fixed interval. Induction of sexual receptivity by hormone priming biases choice toward sex over food and this change is accompanied by an increase in motivation for sex but a decrease in motivation for food. This work provides evidence in support of a novel framework for understanding how the release of ovarian hormones over the course of the estrous cycle modulates adaptive behavioral choice in females by directly assessing motivation via operant responding when multiple rewards are available.

Dataset Information

Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.

Publications

Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.

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