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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 -
Biomolecules Jan 2022As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the...
As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients' residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes.
Topics: Animals; Cell Division; Female; Humans; Insulin-Secreting Cells; Islets of Langerhans; Mice; Placenta; Placental Lactogen; Pregnancy; Rats
PubMed: 35204716
DOI: 10.3390/biom12020215 -
Scientific Reports Oct 2022The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized...
The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized by distinct hormone concentration profiles. Given the difficulty of repeatedly sampling plasma steroid hormones from rodents, the primary method for classifying estrous stage is by identifying vaginal epithelial cell types. However, manual classification of epithelial cell samples is time-intensive and variable, even amongst expert investigators. Here, we use a deep learning approach to achieve classification accuracy at expert level. Due to the heterogeneity and breadth of our input dataset, our deep learning approach ("EstrousNet") is highly generalizable across rodent species, stains, and subjects. The EstrousNet algorithm exploits the temporal dimension of the hormonal cycle by fitting classifications to an archetypal cycle, highlighting possible misclassifications and flagging anestrus phases (e.g., pseudopregnancy). EstrousNet allows for rapid estrous cycle staging, improving the ability of investigators to consider endocrine state in their rodent studies.
Topics: Female; Animals; Rodentia; Deep Learning; Estrus; Estrous Cycle; Hormones
PubMed: 36271290
DOI: 10.1038/s41598-022-22392-w -
Molecular Human Reproduction Mar 2020The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone...
Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.
The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.
Topics: Animals; Aquaporins; Embryo Implantation; Embryo Transfer; Estradiol; Female; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Mifepristone; Ovulation Induction; Pregnancy; Progesterone; Pseudopregnancy; Uterus; Water
PubMed: 31977023
DOI: 10.1093/molehr/gaaa007 -
Life (Basel, Switzerland) May 2022Reliable pregnancy diagnostics would be beneficial for monitoring polar bear () populations both in situ and ex situ, but currently there is no method of non-invasive...
Reliable pregnancy diagnostics would be beneficial for monitoring polar bear () populations both in situ and ex situ, but currently there is no method of non-invasive pregnancy detection in this species. Recent reports in several carnivore species described the identification of fecal proteins that may serve as pregnancy biomarkers; however, repeatability has been limited. The objective of the current analysis was to utilize an unbiased, antibody-free, label-free method for the identification and quantification of fecal proteins to determine if differences associated with pregnancy are detectable in polar bears. Protein was extracted from fecal samples ( = 48) obtained from parturient ( = 6) and non-parturient ( = 6) profiles each at four timepoints: pre-breeding season, embryonic diapause, early placental pregnancy, and mid-placental pregnancy. Protein was prepared and analyzed on the Thermo Orbitrap Eclipse nanoLC-MS/MS system. A total of 312 proteins was identified and quantified; however, coefficients of variation (CV) were high for both abundance ratio variability (384.8 ± 61.0% SEM) and within group variability (86.8 ± 1.5%). Results of this study suggest that the inconsistencies in specific protein concentrations revealed previously by antibody-based assays may not be due to that methodology's limitations, but rather, are reflective of true variation that exists among samples.
PubMed: 35743827
DOI: 10.3390/life12060796 -
Lab Animal Feb 2021For the production and rederivation of mouse strains, pseudopregnant female mice are used for embryo transfer and serve as surrogate mothers to support embryo...
For the production and rederivation of mouse strains, pseudopregnant female mice are used for embryo transfer and serve as surrogate mothers to support embryo development to term. Vasectomized males are commonly used to render pseudopregnancy in females, generated by surgical procedures associated with considerable pain and discomfort. Genetically modified mouse strains with a sterility phenotype provide a non-surgical replacement and represent an important application of the 3Rs (Replacement, Reduction, Refinement). However, the maintenance of such genetically modified mouse strains requires extensive breeding and genotyping procedures, which are regulated procedures under national legislation. As an alternative, we have explored the use of sterile male hybrids that result when two wild-type mouse subspecies, Mus musculus musculus and Mus musculus domesticus, interbreed. We find the male STUSB6F1 hybrid, resulting from the mating of female STUS/Fore with male C57BL/6J, ideally suited and demonstrate that its performance for the production of oviduct and uterine transfer recipients is indistinguishable when compared to surgically vasectomized mice. The use of these sterile hybrids avoids the necessity for surgical procedures or the breeding of sterile genetically modified lines and can be generated by the simple mating of two wild-type laboratory strains-a non-regulated procedure. Furthermore, in contrast with the breeding of genetically sterile mice, all male offspring are sterile and suitable for the generation of pseudopregnancy, allowing their efficient production with minimal breeding pairs.
Topics: Animals; Female; Infertility; Male; Mice; Mice, Inbred C57BL; Phenotype; Pregnancy; Pseudopregnancy; Vasectomy
PubMed: 33398200
DOI: 10.1038/s41684-020-00692-w -
PloS One 2019Recent studies indicate that FoxO1 has roles in female reproductive system, especially in maternal endometrium. Although various cellular aspects and molecular pathways...
Recent studies indicate that FoxO1 has roles in female reproductive system, especially in maternal endometrium. Although various cellular aspects and molecular pathways have been identified, the exact molecular characteristics of embryo implantation are still not completely understood. In this study, we aimed to investigate uterine expression and regulation of FoxO1 during peri-implantation period in mice. Experimental mouse models including, normal pregnancy, pseudopregnancy, artificial decidualization, and delayed implantation and activation were performed. Our results showed that FoxO1 expression was spatiotemporal in mouse endometrial tissue throughout peri-implantation period and its expression was significantly upregulated in luminal and glandular epithelium at the time of implantation. Moreover, on day 5 morning (09:00 AM) of pregnancy, expression of FoxO1 was cytoplasmic in endometrial luminal epithelial cells where embryo homing takes place. With progressing time on day 5 evening (19:00 PM) of pregnancy FoxO1 expression was nuclear in luminal epithelium at implantation site. Pseudopregnancy and artificial decidualization models indicated that FoxO1 expression was regulated by pregnancy hormones. Delayed implantation and activation model indicated that FoxO1 expression at the time of implantation is dependent upon activation status of blastocyst due to E2 induction and uterine sensitivity to implantation. In conclusion, our findings highlight a perspective for FoxO1 expression and regulation in mouse uterus during peri-implantation period indicating that its expression is regulated by implanting embryo and pregnancy hormones.
Topics: Animals; Blastocyst; Decidua; Embryo Implantation, Delayed; Female; Forkhead Box Protein O1; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Pregnancy; Pseudopregnancy
PubMed: 31120913
DOI: 10.1371/journal.pone.0216814 -
Reproduction (Cambridge, England) May 2020We previously demonstrated that 5'-AMP-activated protein kinase (AMPK) is essential for normal reproductive functions in female mice. Conditional ablation of Prkaa1 and...
We previously demonstrated that 5'-AMP-activated protein kinase (AMPK) is essential for normal reproductive functions in female mice. Conditional ablation of Prkaa1 and Prkaa2, genes that encode the α1 and α2 catalytic domains of AMPK, resulted in early reproductive senescence, faulty artificial decidualization, uterine inflammation and fibrotic postparturient endometrial regeneration. We also noted a delay in the timing of embryo implantation in Prkaa1/2d/d female mice, suggesting a role for AMPK in establishing uterine receptivity. As outlined in new studies here, conditional uterine ablation of Prkaa1/2 led to an increase in ESR1 in the uteri of Prkaa1/2d/d mice, resulting in prolonged epithelial cell proliferation and retention of E2-induced gene expression (e.g. Msx1, Muc1, Ltf) through the implantation window. Within the stromal compartment, stromal cell proliferation was reduced by five-fold in Prkaa1/2d/d mice, and this was accompanied by a significant decrease in cell cycle regulatory genes and aberrant expression of decidualization marker genes such as Hand2, Bmp2, Fst and Inhbb. This phenotype is consistent with our prior study, demonstrating a failure of the Prkaa1/2d/d uterus to undergo decidualization. Despite these uterine defects, ovarian function seemed to be normal following ablation of Prkaa1/2 from peri-ovulatory follicles in which ovulation, luteinization and serum progesterone levels were not different on day 5 of pregnancy or pseudopregnancy between Prkaa1/2fl/fl and Prkaa1/2d/d mice. These cumulative findings demonstrate that AMPK activity plays a prominent role in mediating several steroid hormone-dependent events such as epithelial cell proliferation, uterine receptivity and decidualization as pregnancy is established.
Topics: AMP-Activated Protein Kinases; Animals; Cell Proliferation; Embryo Implantation; Epithelial Cells; Estradiol; Estrogen Receptor alpha; Female; Mice; Mice, Knockout; Stromal Cells; Uterus
PubMed: 32191914
DOI: 10.1530/REP-19-0402 -
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 -
Scientific Reports Mar 2023Embryo transfer (ET) is an essential reproductive technology for the production of new animal strains and maintenance of genetic resources. We developed a method, named...
Embryo transfer (ET) is an essential reproductive technology for the production of new animal strains and maintenance of genetic resources. We developed a method, named Easy-ET, to induce pseudopregnancy in female rats by artificial stimulation using sonic vibration instead of mating with vasectomized males. This study examined the application of this method for the induction of pseudopregnancy in mice. Offspring were obtained from two-cell embryos transferred into females with pseudopregnancy induced using sonic vibration in proestrus on the day before embryo transfer. Furthermore, high developmental rates of offspring were observed when pronuclear and two-cell embryos were transferred to females in estrus that were stimulated on the day of embryo transfer. Genome-edited mice were also obtained using frozen-warmed pronuclear embryos with clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system (Cas) nucleases introduced using the technique for animal knockout system by electroporation (TAKE) method, which were transferred to females with pseudopregnancy induced on the day of embryo transfer. This study demonstrated that induction of pseudopregnancy by sonic vibration was also possible in mice.
Topics: Female; Male; Pregnancy; Mice; Rats; Animals; Pseudopregnancy; Vibration; Conversion Disorder; Delusions; Cell Communication
PubMed: 36869082
DOI: 10.1038/s41598-023-30774-x