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Transplantation Oct 2023Uterus transplantation (UTx) is one of the potential methods to cure absolute uterine factor infertility of transgender. However, this mostly comes with many...
BACKGROUND
Uterus transplantation (UTx) is one of the potential methods to cure absolute uterine factor infertility of transgender. However, this mostly comes with many technological challenges.
METHODS
Left inguinal UTx was performed in 13 castrated male rats. End-to-end anastomosis of donor common iliac vessels to recipient femoral vessels was used for transsexual UTx. Sampling was performed on day 30 after transplantation. Grafts were used to analyze the histological changes. TUNEL assay was applied to stain the apoptotic cells. Immunological rejection was judged by flow cytometry.
RESULTS
Six uteri, 4 ovaries, and 4 upper vaginas were found at day 30 posttransplantation. Similar histological changes to proestrus, estrus, and diestrus of female rats were examined in the transplanted uteri. The histological changes of transplanted vaginas showed similarity to proestrus, estrus, and metestrus of the female rats. Follicles of different stages and corpus luteum with distinct morphological appearances were also observed. The TUNEL assay revealed a higher apoptosis of granulosa cells in transplanted ovaries compared with normal ovaries.
CONCLUSIONS
A rat model of transsexual unilateral inguinal uterine transplantation in castrated rats was established, which will provide a reference for bilateral transsexual UTx in animals and genetically 46 XY individuals who wish to become real women through transsexual UTx.
Topics: Humans; Rats; Female; Male; Animals; Uterus; Tissue Donors
PubMed: 37122083
DOI: 10.1097/TP.0000000000004599 -
Frontiers in Endocrinology 2023Neuroendocrine alterations in the mid-life hypothalamus coupled with reproductive decline herald the initiation of menopausal transition. The certain feature and...
BACKGROUND
Neuroendocrine alterations in the mid-life hypothalamus coupled with reproductive decline herald the initiation of menopausal transition. The certain feature and contribution of gut microflora and metabolites to neuroendocrine changes in the menopausal transition remain largely unknown.
METHODS
Fecal samples of rats experiencing different reproductive stages were collected and processed for 16S rRNA and liquid chromatography-mass spectrometry sequencing. The differences of gut microbiota and metabolites between young and middle-aged rats during proestrus and diestrus were analyzed, and their relationships to neuroendocrine aging were then examined.
RESULTS
At the genus level, were abundant at proestrus, while were enriched in the diestrus of middle-aged rats. were found abundant during proestrus instead, while were enriched at the diestrus of young female individuals. Discriminatory metabolites were identified involving 90 metabolic pathways among the animal sets, which were enriched for steroid hormone biosynthesis, arachidonic metabolism, primary bile acid synthesis, and ovarian steroidogenesis. A total of 21 metabolites lacking in hormone-associated changes in middle-aged female individuals presented positive or negative correlations with the circulating luteinizing hormone, bile acid, fibroblast growth factor 19, and gut hormones. Moreover, close correlations were detected between the intestinal bacteria and their metabolites.
CONCLUSION
This study documents specific gut microbial composition changes and concomitant shifting trends of metabolites during menopausal transition, which may initiate the gut-brain dysfunction in neuroendocrine aging.
Topics: Rats; Female; Animals; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Luteinizing Hormone; Aging; Menopause; Estrus; Bile Acids and Salts
PubMed: 38161977
DOI: 10.3389/fendo.2023.1282694 -
PloS One 2023Sex hormones exert a wide influence on several systems of the human body, especially in women, who undergo intense changes in the trans and postmenopausal periods....
Sex hormones exert a wide influence on several systems of the human body, especially in women, who undergo intense changes in the trans and postmenopausal periods. Different experimental models are used to mimic these conditions; however, the impact on hormonal profile may be different. This study aimed to analyze and compare vaginal cytology of different post-estropausal mice models, along with their microscopical ovarian features. Forty-six C57BL/6J female mice with the ages of 4, 6 and 18 months at the beginning of the experiment, weighing about 25-28 grams, constituted five groups: NC-(negative control) animals with no treatment, OVX-SHAM-sham ovariectomized, OVX-ovariectomized, VCD-medicated with 160 mg/kg/day of 4-vinylcyclohexene diepoxide via IP for 20 consecutive days, and Aged-senescent mice under physiological estropause. Euthanasia was performed at different periods for the removal of the ovaries, and after diestrus was confirmed by vaginal cytology for 10 consecutive days. For daily vaginal cytology, morphological and histomorphometric microscopic analyzes were performed. Aged mice presented significant increased neutrophils when compared to VCD group, as well as increased cornified epithelial cells when compared to OVX mice, and also increased nucleated epithelial cells when compared to VCD and OVX. NC and OVX-SHAM ovaries presented innumerous follicles at different stages of development, while VCD showed marked follicular atresia, depleted of primordial or developing follicles and a predominance of interstitial cells. The ovaries of aged mice were predominantly constituted by corpus luteum degenerated into corpus albicans, with rare antral follicles. All analyzed models led to different permanent diestrus profiles caused by each model, as indicated by ovarian features. This should be carefully considered when choosing a post-estropausal experimental model, in order to better correlate this challenging phase of female's life with physiological/pathological conditions.
Topics: Humans; Female; Mice; Animals; Aged; Primary Ovarian Insufficiency; Cyclohexanes; Diestrus; Mice, Inbred C57BL; Follicular Atresia; Cyclohexenes; Disease Models, Animal; Menopause, Premature; Vinyl Compounds
PubMed: 38064437
DOI: 10.1371/journal.pone.0284887 -
BioRxiv : the Preprint Server For... Aug 2023Women 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 pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. We measured the pain threshold daily for four days in ovariectomized, estrogen-primed animals treated with progesterone. The pain threshold was lower 2 days later and stayed that way for the duration of the testing. A specific progesterone-receptor (PR) agonist, segesterone, promoted pain, and mice lacking PR in the brain (PRKO) did not experience lowered pain threshold when treated with progesterone or segesterone. PR activation increased the cold sensitivity but did not affect the heat sensitivity and had a small effect on light sensitivity. Finally, we evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin (NTG) when administered sequentially, reduced pain threshold but not separately. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain in women.
PubMed: 37609239
DOI: 10.1101/2023.08.04.552037 -
Zoology (Jena, Germany) Dec 2023Reproduction in female mammals is characterized by major changes in steroid hormone concentrations, which can be linked to fluctuations in energy expenditure (EE)....
Reproduction in female mammals is characterized by major changes in steroid hormone concentrations, which can be linked to fluctuations in energy expenditure (EE). Estradiol and cortisol can increase EE and metabolic rates (MRs), but knowledge on MR changes during the estrous cycle and gestation is scarce for many species. This also applies to the domestic guinea pig, a species exhibiting an exceptional estrous cycle among rodents. In this study, MRs were measured through oxygen (O) consumption in female guinea pigs during different reproductive stages. Mean O consumption over 2.5 h, resting metabolic rate (RMR, lowest and most stable O consumption over 3 min), body mass, fecal estrogen and progesterone, and saliva cortisol concentrations were measured in twelve female guinea pigs in a repeated measurements design during diestrus, estrus, and the second trimester of gestation. In estrus, body mass was significantly lower and estrogen and cortisol concentrations were significantly higher compared to diestrus and gestation. Mean O consumption and RMR both were significantly increased in estrus compared to diestrus. Additionally, a positive effect of body mass on MRs detected during diestrus and gestation was not found during estrus. Mean O consumption was also higher during gestation compared to diestrus, and a significant increase in cortisol concentrations during the 2.5-h MR measurement was recorded. The results indicate that estrus in guinea pigs is energetically demanding, which probably reflects catabolic effects of estrogens and cortisol that uncoupled MRs from body mass. Knowledge on the energetic requirements associated with different reproductive stages is important for future physiological and behavioral studies on female guinea pigs.
Topics: Guinea Pigs; Female; Animals; Hydrocortisone; Reproduction; Estrogens; Estradiol; Progesterone; Mammals
PubMed: 37931560
DOI: 10.1016/j.zool.2023.126132 -
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 -
Neurobiology of Stress Sep 2023Anxiety and depression are highly prevalent psychiatric disorders, affecting approximately 18% of the United States population. Evidence indicates that central oxytocin...
Anxiety and depression are highly prevalent psychiatric disorders, affecting approximately 18% of the United States population. Evidence indicates that central oxytocin mediates social cognition, social bonding, and social anxiety. Although it is well-established that oxytocin ameliorates social deficits, less is known about the therapeutic effects of oxytocin in non-social contexts. We hypothesized that positive effects of oxytocin in social contexts are attributable to intrinsic effects of oxytocin on neural systems that are related to emotion regulation. The present study investigated the effect of intracerebroventricular (ICV) oxytocin administration (i.e., central action) on anxiety- and depression-like behavior in C57Bl/6J mice using non-social tests. Male and female mice received an ICV infusion of vehicle or oxytocin (100, 200, or 500 ng), then were tested in the elevated zero maze (for anxiety-like behavior) and the tail suspension test (for depression-like behavior). Oxytocin dose-dependently increased open zone occupancy and entries in the elevated zero maze and reduced immobility duration in the tail suspension test in both sexes. Oxytocin decreased anxiety and depression-like behavior in male and female mice. The observed effect of oxytocin on anxiolytic-like behavior appeared to be driven by the males. Given the smaller anxiolytic-like effect of oxytocin in the female mice and the established interaction between oxytocin and reproductive hormones (estrogen and progesterone), we also explored whether oxytocin sensitivity in females varies across estrous cycle phases and in ovariectomized females that were or were not supplemented with estrogen or progesterone. Oxytocin reduced anxiety-like behavior in female mice in proestrus/estrus, ovariectomized females (supplemented or not with estrogen or progesterone), but not females in metestrus/diestrus. Additionally, oxytocin reduced depression-like behavior in all groups tested with slight differences across the various hormonal statuses. These results suggest that the effect of oxytocin in depression- and anxiety-like behavior in mice can be influenced by sex and hormonal status.
PubMed: 37706061
DOI: 10.1016/j.ynstr.2023.100567 -
The Journal of Headache and Pain Jul 2023Migraine is more prevalent in females, raising the possibility that sex and gonadal hormones modulate migraine. We recently demonstrated that minimally invasive...
BACKGROUND
Migraine is more prevalent in females, raising the possibility that sex and gonadal hormones modulate migraine. We recently demonstrated that minimally invasive optogenetic spreading depolarization (opto-SD) elicits robust periorbital allodynia. The objective of this study was to test the hypothesis that opto-SD induced migraine-like pain behavior is worse in females and varies during the estrus cycle.
METHODS
Single or repeated opto-SDs were induced in male and female adult Thy1-ChR2-YFP transgenic mice. Von Frey monofilaments were used to test periorbital mechanical allodynia. Mouse grimace was also examined under increasing light intensity to quantify spontaneous discomfort and light-aversive behavior. Vaginal smears were obtained for estrus cycle staging at the end of behavioral testing.
RESULTS
A multi-variable regression analysis was performed using a male and female cohort to test the effect of independent variables on periorbital allodynia. Opto-SD predicted lower periorbital thresholds as compared with sham stimulation (p < 0.0001). Additionally, female sex predicted lower periorbital thresholds compared with males (p = 0.011). There were significant interactions between opto-SD and time (interaction p = 0.030) as animals tended to recover from opto-SD allodynia over time, and between sex and time (p = 0.020) as females tended to take longer to recover. Proestrus, estrus (PE) and metestrus, diestrus (MD) stages were combined to represent high versus low circulating estradiol relative to progesterone, respectively. Multi-variable regression revealed an effect of estrus cycle (p = 0.015) on periorbital thresholds. In the sham group, PE had lower thresholds than MD. However, there was no interaction between opto-SD and the estrus cycle (p = 0.364). Grimace scores were also examined at incremental light intensities. There was an effect of opto-SD (p < 0.0001), light intensity (p = 0.001) and estrus cycle (p = 0.024) on grimace without interaction among them (three-way ANOVA).
CONCLUSIONS
Female sex and estrus stages with high circulating estradiol relative to progesterone lower trigeminal pain thresholds and augment photosensitivity. In females, opto-SD increased pain behavior and photosensitivity irrespective of the estrus stage.
Topics: Rats; Male; Mice; Female; Animals; Hyperalgesia; Rats, Sprague-Dawley; Progesterone; Depression; Optogenetics; Estrus; Migraine Disorders; Pain Threshold; Phenotype; Estradiol
PubMed: 37464297
DOI: 10.1186/s10194-023-01621-1 -
Animal Reproduction Science Aug 2023Phoenixin-14 (PNX-14) is a regulatory neuropeptide encoded by the SMIM20 gene, which has been implicated in the reproductive cycle by modulating the...
Phoenixin-14 (PNX-14) is a regulatory neuropeptide encoded by the SMIM20 gene, which has been implicated in the reproductive cycle by modulating the hypothalamic-pituitary-gonadal (HPG) axis. Recently, we showed that PNX-14 is downregulated in bitches with cystic endometrial hyperplasia and pyometra. The objective of this study was to determine the expression of Smim20, PNX-14, and its putative receptor GRP173 in the canine ovary (both healthy and those with ovarian cysts), periovarian adipose tissue (PAT) and in the endometrium during the oestrous cycle. The expression was analysed by RT-qPCR and Western blot. In tissue sections, peptides were localised by immunofluorescent assays, and blood plasma concentrations of PNX-14 were detected by EIA. The results demonstrated increased levels of PNX in bitches in the anestrus groups compared to diestrus animals. The expression of GPR173 increased in PAT during the diestrus phase and endometrial tissue in late diestrus bitches. In the ovary, strong signals of PNX-14 and GPR173 were detected in the luteal and follicular cells. Furthermore, bitches with cystic ovaries were characterised by elevated circulating PNX levels and a significantly higher expression of PNX and GPR173 in gonadal tissues, when compared with healthy animals. Moreover, a positive correlation between PNX and progesterone in the blood of healthy bitches was noted, which changed to a negative correlation in females affected by cystic ovaries. These studies expand the knowledge regarding the expression and localization of the PNX/GRP173 system in canine reproductive organs during physiological and pathological conditions.
Topics: Female; Animals; Dogs; Neuropeptides; Peptides; Endometrial Hyperplasia; Endometrium; Adipose Tissue; Dog Diseases
PubMed: 37356348
DOI: 10.1016/j.anireprosci.2023.107282 -
Behavioral and Physiological Differences in Female Rabbits at Different Stages of the Estrous Cycle.Animals : An Open Access Journal From... Nov 2023Estrus involves a series of complex physiological signs and changes in behavior before ovulation, which play a crucial role in animal reproduction. However, there have...
Estrus involves a series of complex physiological signs and changes in behavior before ovulation, which play a crucial role in animal reproduction. However, there have been few studies that evaluate behaviors during the different stages of estrus cycle in female rabbits. Therefore, more detailed information is needed on distinguishing the various stages of the estrous cycle. This study explored the behavioral and physiological differences at various estrous cycle stages in female New Zealand White rabbits. The continuous recording method was employed to record the daily behaviors of twenty postpartum female rabbits during the estrous cycle. Compared with the diestrus stage, the duration of foraging and drinking behavior in estrus decreased significantly, and the frequency of grooming and biting behaviors increased ( < 0.05). Differences in reproductive hormone levels (FSH, LH, P, and E) and follicle development were measured at each stage via ELISA and HE staining. The FSH and LH levels showed an increasing trend and then decreased, with the lowest being in late estrus ( < 0.05). The P level was the lowest in estrus ( < 0.05), and E showed a gradually increasing trend. There was no significant difference in the number of primordial follicles at each stage, but the number of primary follicles in estrus was significantly higher than at the other stages ( < 0.05). To further understand the molecular regulation mechanism of the estrous cycle in female rabbits, we analyzed the ovarian transcription patterns of female rabbits in diestrus (D group) and estrus (E group) employing RNA-seq. A total of 967 differentially expressed genes (DEGs) were screened from the ovaries of female rabbits between the diestrus and estrus groups. A KEGG analysis of DEGs enriched in the estrogen signaling pathway, aldosterone synthesis, and secretion pathway, such as and , was performed. The rabbits' behavior, related physiological hormones, and molecular regulation also differed at different estrous cycle stages. The results provide recommendations for the adequate management practices of postpartum re-estrus and breeding female rabbits.
PubMed: 37958169
DOI: 10.3390/ani13213414