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Neurochemical Research Feb 2022Asparagus racemosus Willd. (Family Liliaceae), also known as female reproductive tonic, is traditionally used across the Sub-Himalayan region in Uttarakhand, India for...
Asparagus racemosus Willd. (Family Liliaceae), also known as female reproductive tonic, is traditionally used across the Sub-Himalayan region in Uttarakhand, India for treatment of epilepsy and disorders of female reproductive system. Therefore, in this study, we investigated the anticonvulsant effect of A. racemosus in a mouse model of catamenial epilepsy. We artificially increased progesterone and neurosteroid levels (a state of pseudo-pregnancy) in adult Swiss albino female mice by injecting pregnant mares' serum gonadotropin (PMSG) (5 IU s.c.), followed by human chorionic gonadotropin (HCG) (5 IU s.c.) after 46 h. In the following 10 days, A. racemosus treatment was given along with measurement of progesterone, estradiol, and corticosterone levels in the blood. Neurosteroid withdrawal was induced by finasteride (50 mg/kg, i.p.) on treatment day 9. Twenty-four hours after finasteride administration (day 10 of treatment), seizure susceptibility was evaluated with the sub-convulsant pentylenetetrazole (PTZ) dose (40 mg/kg i.p.). Four hours after PTZ, animals were assessed for depression like phenotypes followed by euthanasia and separation of brain parts (cortex and hippocampus). The results showed that PMSG and HCG treatment elevated progesterone and estradiol levels. Treatment with finasteride increased seizure susceptibility and depression due to decreased progesterone and elevated estrogen levels coupled with decreased monoamine and elevated corticosterone levels. A. racemosus treatment, on the other hand, significantly decreased seizure susceptibility and depression like behaviors, possibly because of increased progesterone, restored estradiol, corticosterone, and monoamine levels. We concluded that herbal formulations using A. racemosus root extracts may be used as monotherapy or adjuvant therapy along with available AEDs for the better and safe management of catamenial epilepsy as well as comorbid depression.
Topics: Animals; Anticonvulsants; Convulsants; Epilepsy, Reflex; Female; Horses; Mice; Pentylenetetrazole; Pregnancy; Progesterone; Seizures
PubMed: 34623565
DOI: 10.1007/s11064-021-03455-2 -
Oxidative Medicine and Cellular... 2021The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of...
The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of reactive oxygen species (ROS) in luteal cell death during luteolysis, while it is unknown how ROS is regulated in this process. Considering the decrease of blood flow and increase of PGF during luteolysis, we hypothesized that the HIF-1 pathway may be involved in the regulation of ROS in the luteal cell of the late corpus luteum (CL). Here, by using a pseudopregnant rat model, we showed that the level of both HIF-1 and its downstream BNIP3 was increased during luteal regression. Consistently, we observed the increase of autophagy level during luteolysis, which is regulated in a Beclin1-independent manner. Comparing with early (Day 7 of pseudopregnancy) and middle CL (Day 14), the level of ROS was significantly increased in late CL, indicating the contribution of oxidative stress in luteolysis. Inhibition of HIF-1 by echinomycin (Ech), a potent HIF-1 inhibitor, ameliorated the upregulation of BNIP3 and NIX, as well as the induction of autophagy and the accumulation of ROS in luteal cells on Day 21 of pseudopregnancy. Morphologically, Ech treatment delayed the atrophy of the luteal structure at the late-luteal stage. An in vitro study indicated that inhibition of HIF-1 can also attenuate PGF -induced ROS and luteal cell apoptosis. Furthermore, the decrease of cell apoptosis can also be observed by ROS inhibition under PGF treatment. Taken together, our results indicated that HIF-1 signaling is involved in the regression of CL by modulating ROS production via orchestrating autophagy. Inhibition of HIF-1 could obviously hamper the apoptosis of luteal cells and the process of luteal regression.
Topics: Animals; Corpus Luteum; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Luteolysis; Pregnancy; Pseudopregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 34512862
DOI: 10.1155/2021/1764929 -
Reproductive Sciences (Thousand Oaks,... Mar 2022Cadherins play an essential role in the attachment of the blastocyst to the endometrium, a process known as endometrial receptivity. Loss of E-cadherin expression is...
Cadherins play an essential role in the attachment of the blastocyst to the endometrium, a process known as endometrial receptivity. Loss of E-cadherin expression is essential during the process, while the expression level of the other cadherin, N-cadherin, has been reported to be altered in cases of infertility. Both E-cadherin and N-cadherin can be regulated by members of the PARP family. Specifically, PARP-2, which is under the epigenetic control of miR-149, has been observed to promote E-cadherin expression in other human cells. We investigated the roles of E-cadherin and N-cadherin in endometrial receptivity using mouse models for normal endometrial receptivity, pseudopregnancy, and LPS-induced endometrial receptivity failure. E-cadherin and phosphorylated E-cadherin were predominantly expressed during pre-receptive stages as well as in the implantation site of the receptive stage, which were observed reduced during the later stages of implantation in both implantation and non-implantation regions, while N-cadherin was detected only at pre-receptive stages. E-cadherin and N-cadherin were also seen in the uterus during pseudopregnancy, showing a downregulation trend during receptive and post-receptive stages. LPS-induced failed endometrial receptivity showed upregulation of E-cadherin and downregulation of N-cadherin. The E-cadherin expression promoter, GSK-3, was lost and its suppressor, SLUG was upregulated during normal course of endometrial receptivity in mouse model, while GSK-3 was increased during LPS-induced failed embryo implantation. In an in vitro model of embryo implantation, E-cadherin expression is promoted by PARP-2 and regulated by miR-149 epigenetically in human endometrium epithelial cells. In conclusion, E-cadherin is predominantly expressed during pre-receptive stage and promoted by PARP-2, which is regulated by miR-149 in the endometrial epithelial cells.
Topics: Animals; Cadherins; Embryo Implantation; Endometrium; Female; Mice; MicroRNAs; Poly(ADP-ribose) Polymerases; Pregnancy; Signal Transduction
PubMed: 34460092
DOI: 10.1007/s43032-021-00710-3 -
Journal of Forensic Sciences Sep 2021Fifteen cases of Fetal Abduction by Maternal Evisceration (FAMAE) reported to the National Center for Missing and Exploited Children during 1987-2011 outline the...
Fifteen cases of Fetal Abduction by Maternal Evisceration (FAMAE) reported to the National Center for Missing and Exploited Children during 1987-2011 outline the findings from a review of the forensic psychiatric considerations and legal course of each of the cases. Most offenders confessed to law enforcement within a short time of being placed under arrest in statements reflecting a continued effort to manage impressions and minimize culpability. Psychiatric assessment is invariably central to the legal disposition of FAMAE cases, as the defendant's goal is to diminish the perception of culpability/criminal responsibility and mitigate sentencing. Of those sentenced in the United States, nine defendants received life without parole, two received the death penalty (one executed), and one received a minimum of 30 years. Two abductors committed suicide and were not sentenced. Proffered diagnoses at trial included psychogenic amnesia, pseudocyesis, dissociative disorder, and delusional disorder; however, these rarely stood up to court scrutiny. Psychiatric experts showed the greatest variance in diagnosis over what to call the feigned pregnancy. In addition to delusional disorder and dissociative disorder, pseudocyesis, factitious disorder/pregnancy, pseudopregnancy, schizophrenia, and PTSD were among the various diagnoses proposed. A differential diagnosis for many FAMAE offenders may also include borderline personality disorder. Future research accounting for those women claiming false pregnancy who do not become homicidal will clarify whether FAMAE is the extreme endpoint of a fertility identity disorder.
Topics: Adolescent; Adult; Crime; Female; Fetus; Forensic Psychiatry; Forensic Psychology; Humans; Mental Disorders; Pregnancy; Pregnant Women; Young Adult
PubMed: 34156091
DOI: 10.1111/1556-4029.14788 -
Animal Reproduction Mar 2021The aim of this research was to evaluate the use of pyridoxine hydrochloride and its associated side effects in the treatment of pseudopregnancy in female dogs. A total...
The aim of this research was to evaluate the use of pyridoxine hydrochloride and its associated side effects in the treatment of pseudopregnancy in female dogs. A total of 40 female dogs, with no defined breed, in non-gestational diestrus, with clinical complaint of milk production were selected. The female dogs were divided into four experimental groups of 10 animals each, treated orally for 20 days with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride (vitamin B6), 5μg/kg/day of cabergoline (G3), and with a placebo, in the case of the control group (G4). The effects of the treatments on milk production were investigated, as well as possible systemic side effects, macroscopic uterine and ovarian alterations, and uterine histology. During the investigated period, G2 and G3 were equally efficient (P>0.05) in lactation suppression, differing (P>0.05) from the other groups. There were no systemic side effects or uterine changes associated with administration of the studied drug. Vitamin B6 (50mg/kg) has shown to be a safe and economically viable alternative for lactation interruption in female dogs with pseudopregnancy.
PubMed: 33936292
DOI: 10.1590/1984-3143-AR2020-0062 -
Theriogenology Jun 2021Canine (Canis familiaris) pseudocyesis, pseudopregnancy, false pregnancy or nervous lactation is a frequent syndrome observed in non-pregnant, late diestrous or early... (Review)
Review
Canine (Canis familiaris) pseudocyesis, pseudopregnancy, false pregnancy or nervous lactation is a frequent syndrome observed in non-pregnant, late diestrous or early anestrous females that is characterized by different degrees of mammary gland enlargement, maternal behavior and lactation. Further education about this frequent canine physiological event is still necessary to ensure optimal diagnosis and treatment strategies. Thus, the aim of this article was to review and update the physiopathology, physical and behavioral signs, diagnosis, treatment and prevention of pseudocyesis in bitches in which it is a clinical problem.
Topics: Animals; Dogs; Female; Lactation; Pregnancy; Pseudopregnancy
PubMed: 33799011
DOI: 10.1016/j.theriogenology.2021.03.014 -
Animal Science Journal = Nihon Chikusan... 2021A study was conducted to investigate whether ovulation in gilts could be synchronized for embryo collection by the administration of estradiol benzoate (EB) or estradiol...
Induction of short-term pseudopregnancy in gilts by the administration of estradiol benzoate or estradiol dipropionate to achieve ovulatory synchronization for embryo collection.
A study was conducted to investigate whether ovulation in gilts could be synchronized for embryo collection by the administration of estradiol benzoate (EB) or estradiol dipropionate (EDP) to induce pseudopregnancy, followed by the treatment with prostaglandin F (PGF ) on 10 days after. Ten gilts each received a total of 20 mg of EB or EDP on Day 10 or EB on Day 10 and 14 to induce pseudopregnancy (Day 0 = onset of estrus). Donors received PGF 10 or 15 days (as a control) after the first administration of estrogens and subsequently eCG and hCG, and were then inseminated artificially. The embryos were collected 7 days after the administration of hCG, and assessed for embryo yield and their developmental stages. All protocols resulted in good embryo yield (9.8-13.2 embryos in average), and the embryos showed average ability to develop to the expanded blastocyst stage (3.29-4.03 as developmental scores) without any significant differences among the protocols. These results suggest that the administration of PGF 10 days after the treatment of gilts with EB or EDP would allow synchronization of ovulation and embryo collection, as well as shortening the period from estrus detection to embryo collection, thus improving embryo collection efficiency.
Topics: Animals; Chorionic Gonadotropin; Dinoprost; Embryo, Mammalian; Embryonic Development; Estradiol; Estrus Synchronization; Female; Insemination, Artificial; Pseudopregnancy; Research Embryo Creation; Swine; Time Factors
PubMed: 33543586
DOI: 10.1111/asj.13480 -
Biological Psychiatry May 2021Estrogen increases dramatically during pregnancy but quickly drops below prepregnancy levels at birth and remains suppressed during the postpartum period. Clinical and...
BACKGROUND
Estrogen increases dramatically during pregnancy but quickly drops below prepregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an estrogen withdrawal state that is related to changes in affect, mood, and behavior. How estrogen withdrawal affects oxytocin (OT) neurocircuitry has not been examined.
METHODS
We used a hormone-simulated pseudopregnancy followed by estrogen withdrawal in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. These hamsters were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Neuroplasticity in OT-producing neurons in the paraventricular nucleus of the hypothalamus and its efferent targets was measured.
RESULTS
Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus maze and open field tests but did not differ from control females in sucrose preference. Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor density in the dorsal raphe nucleus. Finally, blocking OT receptors in the dorsal raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females.
CONCLUSIONS
Estrogen withdrawal induces OT neuroplasticity in the paraventricular nucleus of the hypothalamus and dorsal raphe nucleus to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.
Topics: Anxiety; Dorsal Raphe Nucleus; Estrogens; Female; Humans; Hypothalamus; Oxytocin; Paraventricular Hypothalamic Nucleus; Postpartum Period; Pregnancy
PubMed: 33487439
DOI: 10.1016/j.biopsych.2020.11.016 -
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 -
Cell Proliferation Feb 2021In mammals, early pregnancy is a critical vulnerable period during which complications may arise, including pregnancy failure. Establishment of a maternal endometrial...
BACKGROUND
In mammals, early pregnancy is a critical vulnerable period during which complications may arise, including pregnancy failure. Establishment of a maternal endometrial acceptance phenotype is a prerequisite for semiheterogeneous embryo implantation, comprising the rate-limiting step of early pregnancy.
METHODS
Confocal fluorescence, immunohistochemistry and western blot for nuclear and cytoplasmic protein were used to examine the activation of yes-associated protein (YAP) in uterine tissue and primary endometrial cells. The target binding between miR16a and YAP was verified by dual-luciferase reporter gene assay. The mouse pregnancy model and pseudopregnancy model were used to investigate the role of YAP in the maternal uterus during early pregnancy in vivo.
RESULTS
We showed that YAP translocates into the nucleus in the endometrium of cattle and mice during early pregnancy. Mechanistically, YAP acts as a mediator of ECM rigidity and cell density, which requires the actomyosin cytoskeleton and is partially dependent on the Hippo pathway. Furthermore, we found that the soluble factor IFNτ, which is a ruminant pregnancy recognition factor, also induced activation of YAP by reducing the expression of miR-16a.
CONCLUSIONS
This study revealed that activation of YAP is necessary for early pregnancy in bovines because it induced cell proliferation and established an immunosuppressive local environment that allowed conceptus implantation into the uterine epithelium.
Topics: Adaptor Proteins, Signal Transducing; Animals; Antagomirs; Cattle; Cell Cycle Proteins; Endometrium; Epithelial Cell Adhesion Molecule; Extracellular Matrix; Female; Gene Expression; Hippo Signaling Pathway; Interferon Type I; Male; Mice; MicroRNAs; Muscle Proteins; Pregnancy; Pregnancy Proteins; Protein Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering; Signal Transduction; Uterus; YAP-Signaling Proteins
PubMed: 33393124
DOI: 10.1111/cpr.12976