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Behavioural Brain Research Feb 2018Females are an under-represented research model and the mechanisms through which sleep loss impairs cognition are not clear. Since levels of reproductive hormones and...
Females are an under-represented research model and the mechanisms through which sleep loss impairs cognition are not clear. Since levels of reproductive hormones and the estrous cycle are sensitive to sleep loss and necessary for learning and memory, we hypothesized that sleep deprivation impacts learning and memory in female mice by interfering with the estrous cycle. We used the object recognition task to assess learning and memory in female mice during separate phases of the estrous cycle and after sleep loss. Mice in metestrus/diestrus attended to sample objects less than mice in proestrus/estrus during object acquisition, the first phase of the object recognition task. Subsequently, during the recognition phase of the task, only mice in proestrus/estrus displayed a preference for the novel object. Sleep deprivation for 12h immediately before the object recognition task reduced time attending to sample objects and novel object preference for mice in proestrus/estrus, without changing length of the estrous cycle. These results show that sleep deprived mice in proestrus/estrus had learning deficits and memory impairments, like mice in metestrus/diestrus. Since sleep deprivation did not disrupt the estrous cycle, however, results did not support the hypothesis. Cognitive impairments due to acute sleep loss were not due to alterations to the estrous cycle.
Topics: Animals; Behavior, Animal; Estrous Cycle; Female; Learning; Memory; Metestrus; Mice, Inbred C57BL; Proestrus; Sleep Deprivation
PubMed: 29180134
DOI: 10.1016/j.bbr.2017.11.033 -
Animals : An Open Access Journal From... Mar 2021The reproductive physiology of canids is unique compared to other mammalian species. Specifically, the reproductive cycle of female canids is characterized by extended... (Review)
Review
The reproductive physiology of canids is unique compared to other mammalian species. Specifically, the reproductive cycle of female canids is characterized by extended periods of proestrus and estrus followed by obligatory diestrus and protracted ovarian inactivity (anestrus). Although canid reproduction follows this general pattern, studies have shown variations in reproductive biology among species and geographic regions. Understanding of these differences is critical to the development of assisted reproductive technologies including estrus induction, gamete rescue, and embryo production techniques for canid conservation efforts. This review summarizes current knowledge of canid reproduction, including estrus cyclicity, seasonality, and seminal traits, with the emphasis on species diversity. The application of reproductive technologies in wild canid conservation will also be discussed.
PubMed: 33804569
DOI: 10.3390/ani11030653 -
Biomolecules Jun 2023Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual...
Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident-intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1β2γ2L and α4β3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior.
Topics: Rats; Female; Animals; Rats, Wistar; Receptors, GABA-A; Aggression; Estrus; Pregnanolone
PubMed: 37371597
DOI: 10.3390/biom13061017 -
Toxicological Sciences : An Official... May 2023Phthalates are found in plastic food containers, medical plastics, and personal care products. However, the effects of long-term phthalate exposure on female...
Long-term exposure to di(2-ethylhexyl) phthalate, diisononyl phthalate, and a mixture of phthalates alters estrous cyclicity and/or impairs gestational index and birth rate in mice.
Phthalates are found in plastic food containers, medical plastics, and personal care products. However, the effects of long-term phthalate exposure on female reproduction are unknown. Thus, this study investigated the effects of long-term, dietary phthalate exposure on estrous cyclicity and fertility in female mice. Adult female CD-1 mice were fed chow containing vehicle control (corn oil) or 0.15-1500 ppm of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), or a mixture of phthalates (Mix) containing DEHP, DiNP, benzyl butyl phthalate, di-n-butyl phthalate, diisobutyl phthalate, and diethyl phthalate. Measurements of urinary phthalate metabolites confirmed effective delivery of phthalates. Phthalate consumption for 11 months did not affect body weight compared to control. DEHP exposure at 0.15 ppm for 3 and 5 months increased the time that the mice spent in estrus and decreased the time the mice spent in metestrus/diestrus compared to control. DiNP exposure (0.15-1500 ppm) did not significantly affect time in estrus or metestrus/diestrus compared to control. Mix exposure at 0.15 and 1500 ppm for 3 months decreased the time the mice spent in metestrus/diestrus and increased the time the mice spent in estrus compared to control. DEHP (0.15-1500 ppm) or Mix (0.15-1500 ppm) exposure did not affect fertility-related indices compared to control. However, long-term DiNP exposure at 1500 ppm significantly reduced gestational index and birth rate compared to control. These data indicate that chronic dietary exposure to phthalates alters estrous cyclicity, and long-term exposure to DiNP reduces gestational index and birth rate in mice.
Topics: Mice; Female; Animals; Diethylhexyl Phthalate; Birth Rate; Phthalic Acids; Periodicity
PubMed: 36929940
DOI: 10.1093/toxsci/kfad030 -
Frontiers in Cell and Developmental... 2022Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in...
Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.
PubMed: 36589755
DOI: 10.3389/fcell.2022.983712 -
Animals : An Open Access Journal From... Jan 2023Myeloperoxidase (MPO), as a marker of neutrophil activation, has been associated with equine endometritis. However, in absence of inflammation, MPO is constantly...
Myeloperoxidase (MPO), as a marker of neutrophil activation, has been associated with equine endometritis. However, in absence of inflammation, MPO is constantly detected in the uterine lumen of estrous mares. The aim of this study was to characterize MPO in the uterus of mares under physiological conditions as a first step to better understand the role of this enzyme in equine reproduction. Total and active MPO concentrations were determined, by ELISA and SIEFED assay, respectively, in low-volume lavages from mares in estrus ( = 26), diestrus ( = 18) and anestrus ( = 8) in absence of endometritis. Immunohistochemical analysis was performed on 21 endometrial biopsies randomly selected: estrus ( = 11), diestrus ( = 6) and anestrus ( = 4). MPO, although mostly enzymatically inactive, was present in highly variable concentrations in uterine lavages in all studied phases, with elevated concentrations in estrus and anestrus, while in diestrus, concentrations were much lower. Intracytoplasmic immunoexpression of MPO was detected in the endometrial epithelial cells, neutrophils and glandular secretions. Maximal expression was observed during estrus in mid and basal glands with a predominant intracytoplasmic apical reinforcement. In diestrus, immunopositive glands were sporadic. In anestrus, only the luminal epithelium showed residual MPO immunostaining. These results confirm a constant presence of MPO in the uterine lumen of mares in absence of inflammation, probably as part of the uterine mucosal immune system, and suggest that endometrial cells are a source of uterine MPO under physiological cyclic conditions.
PubMed: 36766264
DOI: 10.3390/ani13030375 -
International Journal of Molecular... Aug 2020The orofacial pain pathway projects to the parabrachial and amygdala, and sex steroids have been shown to affect neuronal activity in these regions. GABA positive cells... (Comparative Study)
Comparative Study
The orofacial pain pathway projects to the parabrachial and amygdala, and sex steroids have been shown to affect neuronal activity in these regions. GABA positive cells in the amygdala are influenced by sex steroid metabolites to affect pain, and sex steroids have been shown to alter the expression of genes in the parabrachial, changing neuronal excitability. Mechanisms by which sex steroids affect amygdala and parabrachial signaling are unclear. The expression of genes in the parabrachial and amygdala in diestrus (low estradiol) and proestrus (high estradiol) female rats were evaluated in this study. First, varicella zoster virus was injected into the whisker pad of female rats to induce a pain response. Second, gene expression was quantitated using RNA-seq one week after injection. Genes that had the greatest change in expression and known to function in pain signaling were selected for the quantitation of protein content. Protein expression of four genes in the parabrachial and seven genes in the amygdala were quantitated by ELISA. In the parabrachial, neurexin 3 (Nrnx3) was elevated at proestrus. Nrnx3 has a role in AMPA receptor and GABA signaling. Neuronatin (Nnat) and protein phosphatase, Mg/Mn dependent 1E (Ppm1e) were elevated in the parabrachial of diestrus animals both genes having a role in pain signaling. Epoxide hydroxylase (Ephx2) was elevated in the parabrachial at proestrus and the vitamin D receptor (Vdr) was elevated in the amygdala. Ephx2 antagonists and vitamin D have been used to treat neuropathic pain. In conclusion, sex steroids regulate genes in the parabrachial and amygdala that might result in the greater pain response observed during diestrus.
Topics: Amygdala; Animals; Diestrus; Epoxide Hydrolases; Female; Gene Expression Regulation; Herpesvirus 3, Human; Injections; Nerve Tissue Proteins; Neuralgia; Proestrus; RNA, Messenger; Rats; Receptors, Calcitriol
PubMed: 32796585
DOI: 10.3390/ijms21165749 -
Animals : An Open Access Journal From... Nov 2022Endometrial immune cells are essential to support uterine functions across the estrous cycle and in preparation for pregnancy. It has been acknowledged that changes in...
Endometrial immune cells are essential to support uterine functions across the estrous cycle and in preparation for pregnancy. It has been acknowledged that changes in phenotype and/or numbers of lymphocytes, such as regulatory T cells (Tregs) and NK cells, might result in lower fertility in women and mice. Little is known about equine endometrial immune cells across the estrous cycle. Here, we compared the populations of endometrial Tregs and NK cells in estrus and diestrus in mares. Endometrial biopsy and blood samples were taken in estrus and diestrus from 11 mares ages 4-12 years. Flow cytometry with anti-CD4, -CD25 and -FOXP3 and anti-NKp46 and -CD3 antibodies was used to determine the populations of Tregs and NK cells, respectively. The concentration of progesterone was measured with chemiluminescence immunoassay. The results were analyzed with paired Student tests. The mean percentage of endometrial CD4FOXP3 Tregs was 13.7 ± 6.2% in diestrus and 14.5 ± 5.9% in estrus, while the mean percentage of endometrial CD4FOXP3CD25 Tregs changed from 3.6 ± 2.1% in diestrus to 2 ± 2% in estrus ( = 0.0947). The mean proportion of CD3NKp46 lymphocytes in the endometrium was not significantly different, with 6 ± 1% in estrus and 6.5 ± 1.4% in diestrus. There was a large variation in the percentage of NK cells between mares of 2.1-12.7%. This study showed, for the first time, the presence of CD4FOXP3CD25 Tregs and CD3NKp46 NK cells in the endometrium of non-pregnant cycling mares. The percentage of Tregs, and to a greater extent NK cells, showed large fluctuations between mares. Both Tregs and NK cells might be important for the preparation of the endometrium for semen deposition and pregnancy; however, further research is required.
PubMed: 36496894
DOI: 10.3390/ani12233373 -
Animals : An Open Access Journal From... Nov 2020Lactic acid bacteria (LAB) dominate human vaginal microbiota and inhibit pathogen proliferation. In other mammals, LAB do not dominate vaginal microbiota, however shifts...
Lactic acid bacteria (LAB) dominate human vaginal microbiota and inhibit pathogen proliferation. In other mammals, LAB do not dominate vaginal microbiota, however shifts of dominant microorganisms occur during ovarian cycle. The study objectives were to characterize equine vaginal microbiota in mares by culture-dependent and independent methods and to describe its variation in estrus and diestrus. Vaginal swabs from 8 healthy adult Arabian mares were obtained in estrus and diestrus. For culture-dependent processing, bacteria were isolated on Columbia blood agar (BA) and Man Rogosa Sharpe (MRS) agar. LAB comprised only 2% of total bacterial isolates and were not related to ovarian phases. For culture-independent processing, V3/V4 variable regions of the 16S ribosomal RNA gene were amplified and sequenced using Illumina Miseq. The diversity and composition of the vaginal microbiota did not change during the estrous cycle. Core equine vaginal microbiome consisted of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria at the phylum level. At the genus level it was defined by , uncultured and . comprised only 0.18% of the taxonomic composition in estrus and 0.37% in diestrus. No differences in the relative abundance of the most abundant phylum or genera were observed between estrus and diestrus samples.
PubMed: 33153053
DOI: 10.3390/ani10112020 -
Reproductive Sciences (Thousand Oaks,... Oct 2022Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein...
Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein cargo of OEVs change during the estrous cycle in mice. This study analyzed the changes in the size distribution and protein cargo of OEVs at four stages of the estrous cycle in mice. The distribution widths of OEVs according to the estrous cycle stage were as follows: proestrus, 20-690 nm in diameter, with two peaks at 50 and 250 nm; estrus, 22-420 nm in diameter, with two peaks at 40 and 200 nm; metestrus, 30-70 nm diameter, with a single peak at 40 nm; and diestrus, 10-26 nm diameter, with a single peak at 20 nm. The estrogen receptor (ER) level in OEVs at the proestrus stage differed significantly from that at estrus (P = 0.013) and diestrus (P = 0.005). The levels of CD9 and Hsc70 fluctuated across the four stages, although with no significant differences. Furthermore, OEVs were observed among the cilia and microvilli of epithelial cells at the proestrus, estrus, and diestrus stages, but not at the metestrus stage. The number of observed OEVs was the highest at the proestrus stage, followed by the estrus, and the diestrus stage. Endosomes were also observed at the estrus and diestrus stages. The change of the OEV size and ER cargo is associated with the estrous cycle in mice. Our findings increase the understanding of the physiological characteristics of OEVs, which may have clinical applications.
Topics: Animals; Estrous Cycle; Extracellular Vesicles; Fallopian Tubes; Female; Humans; Mice; Oviducts; Receptors, Estrogen
PubMed: 35137347
DOI: 10.1007/s43032-022-00862-w