-
Brain, Behavior, and Immunity Jul 2024Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis...
Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.
Topics: Animals; Female; Dysbiosis; Hippocampus; Mice; Gastrointestinal Microbiome; NLR Family, Pyrin Domain-Containing 3 Protein; Disease Models, Animal; Fecal Microbiota Transplantation; Depression, Postpartum; Mice, Inbred C57BL; Depression; Neuroinflammatory Diseases; Behavior, Animal; Anxiety; Brain-Gut Axis; Inflammation; Ovariectomy
PubMed: 38599497
DOI: 10.1016/j.bbi.2024.04.002 -
Molecular Medicine (Cambridge, Mass.) Jul 2023Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the...
BACKGROUND
Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the postpartum period remain largely unknown. Drastic fluctuations in reproductive hormones during the perinatal period generally account for triggering PPD. However, the molecular mechanism underlying the PPD-like behaviors induced by the fluctuations in hormones has rarely been reported.
METHODS
We utilized hormones-simulated pseudopregnancy (HSP) and hormones-simulated postpartum period (HSPP) rat models to determine how drastic fluctuations in hormone levels affect adult neurotransmission and contribute to depressive-like behaviors. The electrophysiological response of CA1 pyramidal neurons was evaluated by whole-cell patch clamping to identify the hormone-induced modulations of neurotransmission. The statistical significance of differences was assessed with One-way ANOVA and t-test (p < 0.05 was considered significant).
RESULTS
Reproductive hormones withdrawal induced depressive-like behaviors and disturbed the balance of excitatory and inhibitory transmission in the pyramidal neurons in the hippocampus. Molecular analyses revealed that the blunted Wnt signaling might be responsible for the deficits of synaptic transmission and behaviors. Activation of Wnt signaling increased excitatory and inhibitory synaptic transmission in the hippocampus. Reactivation of Wnt signaling alleviated the anhedonic behaviors and abnormal synaptic transmission.
CONCLUSIONS
Restoring Wnt signaling in the hormones-simulated postpartum period rat models remediated depression-related anhedonia symptoms and rebalanced the excitation/inhibition ratio by collectively enhancing the plasticity of GABAergic and glutamatergic synapses. The investigations carried out in this research might provide an alternative and prospective treatment strategy for PPD.
Topics: Pregnancy; Humans; Female; Rats; Animals; Depression, Postpartum; Wnt Signaling Pathway; Hippocampus; Synaptic Transmission; Hormones
PubMed: 37491227
DOI: 10.1186/s10020-023-00697-4 -
Genes To Cells : Devoted To Molecular &... Dec 2023A simple method for producing pseudopregnant mice supports pup production. In this study, pregnant ICR were obtained mice without mating with vasectomized mice via...
A simple method for producing pseudopregnant mice supports pup production. In this study, pregnant ICR were obtained mice without mating with vasectomized mice via administration of mouse Kisspeptin-10 (mKp-10) and transferring blastocysts to the uterus. Blastocyst transfer after mKp-10 administration to mice with gapping and reddish pink vagina resulted in 65.2% (15/23) pregnancies, and 39.1% (34/87) of the transferred blastocysts showed full-term growth. Vaginal smears were observed for accurate estrus cycle determination, and subsequent administration of mKp10 to mice during the estrus stage and blastocyst transfer resulted in 95.2% (20/21) pregnancies and 50.7% (104/205) birth rates. Regarding 2-cell transfer after administration of mKp-10, 100% (8/8) of the mice became pregnant, and 45.0% (36/80) of the embryos were born. Administration of mKp-10 to mice during the estrus stage is a convenient way to generate pseudopregnant mice.
Topics: Pregnancy; Female; Mice; Animals; Pseudopregnancy; Mice, Inbred ICR; Uterus; Estrus
PubMed: 37886801
DOI: 10.1111/gtc.13077 -
PloS One 2024Vasectomized mice play a key role in the production of transgenic mice. However, vasectomy can cause great physical and psychological suffering to mice. Therefore, there...
Vasectomized mice play a key role in the production of transgenic mice. However, vasectomy can cause great physical and psychological suffering to mice. Therefore, there is an urgent need to find a suitable replacement for vasectomized mice in the production of transgenic mice. In this study, we generated C57BL/6J mice (Piwil1 D633A-INS99, Piwil1mt/mt) with a 99-base insertion in the Miwi (Piwil1) gene using CRISPR/Cas9 technology and showed that Piwil1mt/+ heterozygous mice were normally fertile and that homozygous Piwil1mt/mt males were sterile and females were fertile. Transplantation of normal fertilized eggs into wild pseudopregnant females following mating with Piwil1mt/mt males produced no Piwil1mt/mt genotype offspring, and the number of offspring did not differ significantly from that of pseudopregnant mice following mating and breeding with ligated males. The CRISPR‒Cas9 system is available for generating Miwi-modified mice, and provides a powerful resource to replace ligated males in assisted reproduction research.
Topics: Animals; Female; Male; Mice; Argonaute Proteins; CRISPR-Cas Systems; Mice, Inbred C57BL; Mice, Transgenic; Pseudopregnancy
PubMed: 38771805
DOI: 10.1371/journal.pone.0296414 -
Indian Journal of Psychiatry Jul 2023Pseudo-pregnancy is an uncommon psychiatric presentation, often having a complex interplay of psycho-social factors making it difficult to manage. It is common to...
Pseudo-pregnancy is an uncommon psychiatric presentation, often having a complex interplay of psycho-social factors making it difficult to manage. It is common to present in the reproductive age range, rarely in postmenopausal women. We are reporting a rare presentation of a 48-year post-menopausal widowed HIV-positive female with no live issues having two years of secondary amenorrhea complaining to have documented weight gain and experience of perceiving fetal movements for the past 5 months. However, she persistently insisted on antenatal care despite repeated reports of ultra-sonographic pelvis imaging and gynecological examination pointed toward menopausal changes and the absence of any live issue. This case report emphasizes the clinical presentation and management strategies for patients with pseudocyesis, a peculiar and rare psychiatric manifestation.
PubMed: 37645358
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_430_22 -
Journal of Veterinary Internal Medicine 2024Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the...
BACKGROUND
Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited.
HYPOTHESIS
Estrous stage may influence thyroid function in German Shepherd dogs.
METHODS
Longitudinal, observational, non-randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17-β-estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period.
ANIMALS
Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism.
RESULTS
Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17-β-estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17-β-estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy.
CONCLUSIONS
Different stages of estrus can influence the measurement of TT4 in female dogs.
Topics: Humans; Pregnancy; Dogs; Animals; Female; Thyroxine; Triiodothyronine; Thyroid Gland; Cohort Studies; Progesterone; Thyroid Hormones; Thyrotropin; Gonadal Steroid Hormones; Estradiol
PubMed: 38093496
DOI: 10.1111/jvim.16959 -
Journal of Visualized Experiments : JoVE Jul 2023For successfully maintaining pregnancy with embryo transfer or artificial insemination, female recipient mice must be induced into a pseudopregnant state. Female mice...
For successfully maintaining pregnancy with embryo transfer or artificial insemination, female recipient mice must be induced into a pseudopregnant state. Female mice are traditionally paired overnight with vasectomized males, and the following morning, the presence of a copulation plug is assessed. To increase the efficiency of producing pseudopregnant females, a cervical manipulation technique has been standardized to be used in combination with non-surgical embryo transfer or artificial insemination techniques in mice. The blunt end of a small plastic rod is inserted vaginally to contact the cervix and is vibrated for 30 s by contact with a trimmer. The procedure is quick and does not require anesthesia or analgesia. This technique increases the reliability and predictability of producing pseudopregnant females and entirely eliminates the requirement for vasectomized males. For CD1 mice, the efficiency of pseudopregnancy induction using cervical manipulation was 83% for females in estrus (N = 76) but only 38% of females in estrus were plugged by vasectomized males (N = 24). Artificial insemination in CD1 mice was performed by estrus synchronization with hormones, cervical manipulation, and the uterine transfer of sperm. Artificial insemination recipients receiving cervical manipulation (N = 76) had a pregnancy rate of 72% and an average litter size of 8.3 pups. This method can also be used to produce pseudopregnant females for non-surgical embryo transfer. Therefore, inducing pseudopregnancy by cervical manipulation is a convenient and efficient alternative to mating with a vasectomized male when performing non-surgical assisted reproduction techniques. Using cervical manipulation provides 3Rs (replacement, reduction, and refinement) benefits for assisted reproduction techniques by reducing the number of animals required and eliminating the necessity for surgically altered males.
Topics: Pregnancy; Male; Mice; Female; Animals; Pseudopregnancy; Reproducibility of Results; Semen; Embryo Transfer; Insemination, Artificial
PubMed: 37486140
DOI: 10.3791/65477 -
International Journal of Fertility &... Aug 2023Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterine tissue. Women undergoing assisted reproductive technologies (ART),...
BACKGROUND
Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterine tissue. Women undergoing assisted reproductive technologies (ART), particularly frozen embryo transfer (FET), are in high-risk populations for EP. , fibroblast growth factor-2 , and Heparin-binding epidermal growth factor genes are involved in the endometrial receptivity pathway, leading to normal eutopic implantation; Although, their relevance in the tubal pregnancy after FET is unknown. We aimed evaluation of and expression fold as endometrial receptive markers in the EP patients following the FET cycle.
MATERIALS AND METHODS
A case-control study was conducted on ten patients (five EP patients and five women in the pseudo-pregnancy group, as the control samples). Pseudo-pregnancy group was established in women who were candidates for hysterectomy for benign diseases. Fallopian tube biopsies and corresponding endometrial tissues from these patients were taken during the hysterectomy. However, the fallopian tube and endometrial tissues of EP patients were obtained during salpingectomy. The mRNA expressions of and genes in the fallopian tube and endometrial tissues were measured by real-time polymerase chain reaction (PCR) assay.
RESULTS
MUC1 mRNA expression level in the endometrium of the case group was higher than in the control group (P=0.04); however, its mRNA expression in the fallopian samples of the case group in comparison with the control group was significantly decreased (P=0.001). The mRNA expression level was not significantly different between the case and control endometrium, whereas its expression was significantly increased in the case fallopian samples compared with the control ones (P=0.001). The same pattern was observed for mRNA expression level in the fallopian samples of the case group but was significantly reduced in the endometrial samples in comparison with the control samples (P=0.03).
CONCLUSION
and gene mRNA expression changes may explain the embryo rejection from the uterus and the establishment of a receptive phenotype in fallopian cells.
PubMed: 37577906
DOI: 10.22074/ijfs.2023.1972252.1390 -
BioRxiv : the Preprint Server For... May 2024The menstrual cycle influences the risk of acquiring sexually transmitted infections (STIs), including (), although the underlying immune contributions are poorly...
The menstrual cycle influences the risk of acquiring sexually transmitted infections (STIs), including (), although the underlying immune contributions are poorly defined. A mouse model simulating the immune-mediated process of menstruation could provide valuable insights into tissue-specific determinants of protection against chlamydial infection within the cervicovaginal and uterine mucosae comprising the female reproductive tract (FRT). Here, we used the pseudopregnancy approach in naïve C57Bl/6 mice and performed vaginal challenge with () at decidualization, endometrial tissue remodeling, or uterine repair. This strategy identified that the time frame comprising uterine repair correlated with robust infection and greater bacterial burden as compared with mice on hormonal contraception, while challenges during endometrial remodeling were least likely to result in a productive infection. By comparing the infection site at early time points following chlamydial challenge, we found that a greater abundance of innate effector populations and proinflammatory signaling, including IFNγ correlated with protection. FRT immune profiling in uninfected mice over pseudopregnancy or in pig-tailed macaques over the menstrual cycle identified NK cell infiltration into the cervicovaginal tissues and lumen over the course of endometrial remodeling. Notably, NK cell depletion over this time frame reversed protection, with mice now productively infected with following challenge. This study shows that the pseudopregnancy murine menstruation model recapitulates immune changes in the FRT as a result of endometrial remodeling and identifies NK cell localization at the FRT as essential for immune protection against primary infection.
PubMed: 38826233
DOI: 10.1101/2024.05.21.595090 -
Life (Basel, Switzerland) Jan 2024Polar bears () face a number of challenges that threaten the survival of the species. Captive breeding represents one essential facet of species conservation, but...
Polar bears () face a number of challenges that threaten the survival of the species. Captive breeding represents one essential facet of species conservation, but aspects of the polar bear's reproductive physiology, such as follicle maturation, coitus-induced ovulation, and pseudopregnancy, are poorly characterized and present challenges for enhancing natural reproductive success and the application of advanced reproductive techniques. Due to the absence of a reliable transrectal or transabdominal ultrasound method for ovarian examination in the species, the ovaries of two adult female polar bears were examined laparoscopically to evaluate the feasibility of surgical access to the ovaries, oviduct, and uterus. The minimally invasive procedure was easily and rapidly performed in both bears and all procedures. Direct visual assessment of the ovary was possible after dissection of a fatty bursal sac, which completely enclosed the ovaries. In the second bear, laparoscopic manipulation of the ovary to draw it closer to the body wall enabled transcutaneous ultrasound. Laparoscopy may be a valuable tool to aid in the application of advanced reproductive technologies in polar bears.
PubMed: 38255720
DOI: 10.3390/life14010105