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PloS One 2024During the oestrous cycle, the bovine endometrium undergoes morphological and functional changes, which are regulated by alterations in the levels of oestrogen and...
During the oestrous cycle, the bovine endometrium undergoes morphological and functional changes, which are regulated by alterations in the levels of oestrogen and progesterone and consequent changes in gene expression. To clarify these changes before and after oestrus, RNA-seq was used to profile the transcriptome of oestrus-synchronized beef heifers. Endometrial samples were collected from 29 animals, which were slaughtered in six groups beginning 12 h after the withdrawal of intravaginal progesterone releasing devices until seven days post-oestrus onset (luteal phase). The groups represented proestrus, early oestrus, metoestrus and early dioestrus (luteal phase). Changes in gene expression were estimated relative to gene expression at oestrus. Ingenuity Pathway Analysis (IPA) was used to identify canonical pathways and functional processes of biological importance. A total of 5,845 differentially expressed genes (DEGs) were identified. The lowest number of DEGs was observed at the 12 h post-oestrus time point, whereas the greatest number was observed at Day 7 post-oestrus onset (luteal phase). A total of 2,748 DEGs at this time point did not overlap with any other time points. Prior to oestrus, Neurological disease and Organismal injury and abnormalities appeared among the top IPA diseases and functions categories, with upregulation of genes involved in neurogenesis. Lipid metabolism was upregulated before oestrus and downregulated at 48h post-oestrus, at which point an upregulation of immune-related pathways was observed. In contrast, in the luteal phase the Lipid metabolism and Small molecule biochemistry pathways were upregulated.
Topics: Cattle; Animals; Female; Progesterone; Estrus; Endometrium; Gene Expression Profiling; Transcriptome
PubMed: 38547106
DOI: 10.1371/journal.pone.0301005 -
Molecular Reproduction and Development Jan 2024Cystic ovary disease (COD) is a common cause of subfertility in dairy cattle. Therefore, the aim of this study was to provide novel concepts for cyst classification and...
Cystic ovary disease (COD) is a common cause of subfertility in dairy cattle. Therefore, the aim of this study was to provide novel concepts for cyst classification and to investigate the effects of COD on tubal microarchitecture, oviductal metabolic function, and the formation of the sperm reservoir. Bovine Fallopian tubes affected by follicular cysts, follicular cysts with luteinization and luteal cysts were investigated by a variety of microscopic and histological techniques and compared to control cows in metestrus and diestrus. We defined three types of cysts involved in COD, each of which had a characteristic wall thickness, inner wall appearance and cellular pattern within the cyst aspirate. Regarding the Fallopian tube, each cyst type was associated with a characteristic morphology, specifically the microarchitecture of the folds in ampulla, epithelial cell ratios, and ciliated/secretory cell size and form. Furthermore, each cyst type showed different patterns of tubal glycoprotein and acidic mucopolysaccharide synthesis, which was highly variable as compared to the controls. Our studies are the first to characterize the effects of COD on the Fallopian tube, which promotes the establishment of novel, cyst-specific therapeutic concepts in cattle and helps gain a holistic view of the causes of subfertility in cows with COD.
Topics: Male; Female; Humans; Cattle; Animals; Fallopian Tubes; Semen; Ovarian Cysts; Infertility
PubMed: 38282319
DOI: 10.1002/mrd.23725 -
Animal Biotechnology Dec 2023Estrus detection is a major problem in buffaloes because of the poor expression of estrus signs leading to low reproductive efficiency. Salivary transcripts analysis is...
Estrus detection is a major problem in buffaloes because of the poor expression of estrus signs leading to low reproductive efficiency. Salivary transcripts analysis is a promising tool to identify biomarkers; therefore, the present study was carried out to evaluate their potential as estrus biomarkers. The levels of , , , transcripts were compared in saliva during estrous cycle stages [early proestrus (day -2, EP), late proestrus (day-1, LP), estrus (E), metestrus (ME) and diestrus (DE)] of cyclic heifers ( = 8) and pluriparous ( = 8) buffaloes by employing quantitative real-time polymerase chain reaction (qRT-PCR). The levels of (EP/DE 1.46-2.43 fold, LP/DE 2.49-3.06 fold; E/DE 7.21-11.9-fold < 0.01; ME/D 1.0-1.16 fold) and (EP/DE 0.93-2.39 fold, LP/DE 2.68-3.23 fold; E/DE 8.52-15.18 fold < 0.01; ME/D 0.86-1.01 fold) were significantly altered during the estrus than other estrous cycle stages in both cyclic heifers and pluriparous buffaloes. Receiver operating characteristic curve analysis revealed the ability of salivary (AUC 0.96; < 0.001) and (AUC 0.99; < 0.01) to differentiate E from other stages of the estrous cycle. Significantly higher levels of and transcripts in saliva during the estrus phase suggest their biomarkers potential for estrus detection in buffaloes.
Topics: Female; Animals; Cattle; Buffaloes; Estrus; Estrous Cycle; Biomarkers
PubMed: 35913775
DOI: 10.1080/10495398.2022.2105228 -
Peptides Oct 2023Neuropeptide B (NPB) has been identified as an endogenous peptide ligand for the orphan receptor NPBWR1. However, the effect of NPB on the central regulatory mechanisms...
Neuropeptide B (NPB) has been identified as an endogenous peptide ligand for the orphan receptor NPBWR1. However, the effect of NPB on the central regulatory mechanisms of reproductive functions remains unclear. Our findings indicated the presence of Npb, Npw (which is another ligand for NPBWR1), and Npbwr1 mRNA in the hypothalamus of male and female rats at each stage of the estrous cycle. Npb mRNA expression was found to be significantly higher in diestrus compared to estrus. The expression of Npw mRNA was one order of magnitude lower than that of Npb mRNA, and Npw mRNA expression in diestrus was significantly higher than that in the other stages of the estrous cycle. Furthermore, Npbwr1 mRNA expression was found to be significantly higher in diestrus compared to the other stages of the estrous cycle and intact males. Notably, estrogen did not alter the expression of Npb, Npw, and Npbwr1 mRNAs in the hypothalamus of females. Central injection of NPB increased plasma luteinizing hormone (LH) levels in both intact males and estrogen-primed ovariectomized females but not in ovariectomized females. These results suggest that NPB-NPBWR1 signaling would be a facilitatory regulatory mechanism in the reproductive function of male and female rats. To the best of our knowledge, this study is the first report to describe the central role of NPB-NPBWR1 signaling in LH regulation in mammals.
Topics: Rats; Animals; Female; Male; Receptors, Neuropeptide; Ligands; Luteinizing Hormone; RNA, Messenger; Estrogens; Mammals
PubMed: 37507090
DOI: 10.1016/j.peptides.2023.171064 -
International Journal of Molecular... May 2024Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent...
Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in , causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.
Topics: Animals; Adrenal Hyperplasia, Congenital; Disease Models, Animal; Steroid 21-Hydroxylase; Mice; Female; Male; Humans; Corticosterone; Aldosterone; Adrenal Glands; Mutation; Progesterone
PubMed: 38791102
DOI: 10.3390/ijms25105062 -
Psychoneuroendocrinology Mar 2024Mood disorders, like major depressive disorder, can be precipitated by chronic stress and are more likely to be diagnosed in cisgender women than in cisgender men. This...
Mood disorders, like major depressive disorder, can be precipitated by chronic stress and are more likely to be diagnosed in cisgender women than in cisgender men. This suggests that stress signaling in the brain is sexually dimorphic. We used a chronic variable mild stress paradigm to stress female and male mice for 6 weeks, followed by an assessment of avoidance behavior: the open field test, the elevated plus maze, the light/dark box emergence test, and the novelty suppressed feeding test. Additional cohorts were used for bulk RNA-Sequencing of the anterodorsal bed nucleus of the stria terminalis (adBNST) and whole-cell patch clamp electrophysiology in NPY-expressing neurons of the adBNST to record stress-sensitive M-currents. Our results indicate that females are more affected by chronic stress as indicated by an increase in avoidance behaviors, but that this is also dependent on the estrous stage of the animals such that diestrus females show more avoidant behaviors regardless of stress treatment. Results also indicate that NPY-expressing neurons of the adBNST are not major mediators of chronic stress as the M-current was not affected by treatment. RNA-Sequencing data suggests sex differences in estrogen signaling, serotonin signaling, and orexin signaling in the adBNST. Our results indicate that chronic stress influences behavior in a sex- and estrous stage-dependent manner but NPY-expressing neurons in the BNST are not the mediators of these effects.
Topics: Humans; Mice; Female; Male; Animals; Septal Nuclei; Depressive Disorder, Major; Neurons; Signal Transduction; RNA
PubMed: 38128260
DOI: 10.1016/j.psyneuen.2023.106920 -
Reproduction (Cambridge, England) Dec 2023The SCN regulates ovulation by stimulating the preovulatory surge of gonadotropins. This study revealed an additional role in the sensitization of the hypothalamus to...
IN BRIEF
The SCN regulates ovulation by stimulating the preovulatory surge of gonadotropins. This study revealed an additional role in the sensitization of the hypothalamus to estradiol that changes along the estrous cycle and the side of the nucleus.
ABSTRACT
Ovulation is timed by neural signals originating at the suprachiasmatic nucleus (SCN) that trigger ovulation when converge with high estradiol levels, which indicates the maturation of ovarian follicles. We have shown that the hypothalamic regulation of ovulation is asymmetrical and we hypothesized that the paired SCN could contribute to such symmetries. We unilaterally lesioned the SCN of rats at each stage of the estrous cycle and evaluated the acute effects on the progression of their estrous cycle, follicular development and ovulation. Lesions prevented progression of the estrous cycle when performed in estrus/metestrus but not in diestrus/proestrus. Abnormalities in follicular development were observed in the nonovulating lesioned rats and this was independent of the side of the SCN destroyed and the stage of the cycle when surgery was performed. Groups of lesioned rats were then hormonally primed with GnRH or estradiol to assess the neuroendocrine pathway altered by the treatment. GnRH restored ovulation, suggesting that both SCN are needed for proper triggering of the preovulatory surge of GnRH and that unilateral lesion does not impair the sensitivity of the pituitary or the ovary to GnRH and gonadotropins, respectively. With regard to restoring ovulation, estradiol was asymmetrically effective in rats lesioned in estrous, partially effective in rats operated at diestrus and ineffective in rats at metestrus. Our results indicate that the SCN regulates the activity of the hypothalamic-pituitary-ovarian axis not only by modulating the preovulatory surge of GnRH/gonadotropins but also by promoting the hypothalamic integration of estrogenic signals from the ovaries in an asymmetric and stage-dependent fashion.
Topics: Female; Rats; Animals; Estradiol; Feedback; Estrous Cycle; Suprachiasmatic Nucleus; Gonadotropin-Releasing Hormone; Ovulation; Gonadotropins
PubMed: 37855440
DOI: 10.1530/REP-23-0178 -
The Journal of Pain Mar 2024Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain...
Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to mechanical stimulus during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. Progesterone treatment of ovariectomized and estrogen-primed mice caused a delayed reduction in the mechanical threshold. Segesterone, a specific agonist of PRs replicated this effect, whereas, the segesterone-induced reduction in mechanical threshold was blocked in the mice lacking PRs in the nervous system. Segesterone treatment also did not alter mechanical threshold in adult male and juvenile female mice. PR activation increased the cold sensitivity but did not affect the heat and light sensitivity. We evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin when administered sequentially, reduced the pain threshold but not when given separately. PRs were expressed in several components of the migraine ascending pain pathway, and their deletion blocked the painful effects of nitroglycerin. PR activation also increased the number of active neurons in the components of the migraine ascending pain pathway. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain and migraine in women. PERSPECTIVE: This article provides evidence for the role of progesterone receptors in regulating pain sensitivity and migraine susceptibility in females. Progesterone receptors may be a therapeutic target to treat chronic pain conditions more prevalent in women than men.
Topics: Humans; Female; Male; Mice; Animals; Receptors, Progesterone; Progesterone; Chronic Pain; Nitroglycerin; Migraine Disorders; Estrogens
PubMed: 37777034
DOI: 10.1016/j.jpain.2023.09.017 -
Biology of Reproduction Jun 2024Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent....
Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent. Even still, uterine contractions have primarily been studied in the context of preterm labor. This is partly due to a lack of methods for studying the uterine muscle contractility in the intact organ. Here, we describe an imaging-based method to evaluate mouse uterine contractility of both the longitudinal and circular muscles in the cycling stages and in early pregnancy. By transforming the image-based data into three-dimensional spatiotemporal contractility maps, we calculate waveform characteristics of muscle contractions, including amplitude, frequency, wavelength, and velocity. We report that the native organ is highly contractile during the progesterone-dominant diestrus stage of the cycle when compared to the estrogen-dominant proestrus and estrus stages. We also observed that during the first phase of uterine embryo movement when clustered embryos move toward the middle of the uterine horn, contractions are dynamic and non-uniform between different segments of the uterine horn. In the second phase of embryo movement, contractions are more uniform and rhythmic throughout the uterine horn. Finally, in Lpar3-/- uteri, which display faster embryo movement, we observe global and regional increases in contractility. Our method provides a means to understand the wave characteristics of uterine smooth muscle in response to modulators and in genetic mutants. Better understanding uterine contractility in the early pregnancy stages is critical for the advancement of artificial reproductive technologies and a possibility of modulating embryo movement during clinical embryo transfers.
Topics: Female; Animals; Uterine Contraction; Pregnancy; Mice; Uterus; Estrous Cycle
PubMed: 38713674
DOI: 10.1093/biolre/ioae071 -
Neurobiology of Learning and Memory Dec 2023The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial...
The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial learning, as well as explorative behaviors in female rats. We used the hippocampus-dependent Open-field Tower Maze (OFTM) task to assess acquisition followed by a retention test (reacquisition) that was given 48 h later. Immediately prior to acquisition, experimental rats were exposed to an acute restraint stress and were trained under bright lights. Female rats' estrous cycles were tracked throughout training and testing. Exposure to stress did not affect learning when levels of estrogens were low (i.e., during estrus and metestrus). However, acute stress exposure significantly lowered spatial acquisition of the female rats in the phases with rising levels of estrogens (i.e., during diestrus and proestrus). Furthermore, this stress-induced diminishment during acquisition was evident at the beginning of the retention without any presentation of stress. The present findings provide insight about the interactive relationship between stress and sex hormones on cognitive functions.
Topics: Rats; Female; Animals; Spatial Learning; Maze Learning; Estrous Cycle; Estrogens; Cognition
PubMed: 37944635
DOI: 10.1016/j.nlm.2023.107862