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Reproductive Sciences (Thousand Oaks,... Jan 2021It has been well established that uterine function during the peri-implantation period is precisely regulated by ovarian estrogen and progesterone. The embryo enters the...
It has been well established that uterine function during the peri-implantation period is precisely regulated by ovarian estrogen and progesterone. The embryo enters the uterine cavity before implantation. However, the impact of pre-implantation embryo on uterine function is largely unknown. In the present study, we performed RNA-seq analysis of mouse uterus on day 4 morning of natural pregnancy (with embryos in the uterus) and pseudo-pregnancy (without embryos in the uterus). We found that 146 genes were upregulated, and 77 genes were downregulated by the pre-implantation embryo. Gene ontology and gene network analysis highlighted the activation of inflammatory reaction in the uterus. By examining the promoter region of differentially expressed genes, we found that NF-kappaB was a causal transcription factor. Finally, we validated 4 inflammation-related genes by quantitative RT-PCR. These 4 genes are likely the main mediators of the inflammatory reaction in the uterus triggered by the pre-implantation embryo. Our data indicated that the pre-implantation embryo causes uterine inflammatory reaction, which in turn might contribute to the establishment of uterine receptivity and embryo implantation.
Topics: Animals; Blastocyst; Chemokines, CXC; Cyclooxygenase 2; Embryo Implantation; Female; Gene Regulatory Networks; Inflammation Mediators; Interleukins; Mice; NF-kappa B; Pregnancy; Pseudopregnancy; RNA-Seq; Uterus
PubMed: 32651899
DOI: 10.1007/s43032-020-00259-7 -
Reproductive Toxicology (Elmsford, N.Y.) Dec 2019Our understanding of the relationship between stress-derived epinephrine and early pregnancy failure remains incomplete. Here, we explored the effect of epinephrine...
Our understanding of the relationship between stress-derived epinephrine and early pregnancy failure remains incomplete. Here, we explored the effect of epinephrine exposure on early pregnancy and pseudopregnancy in mice. Increased expression of adrenergic receptors Adra1b, Adra2b and Adrb2 was observed during decidualization and post-implantation embryogenesis was delayed or survival impaired. Epinephrine treatment also impaired decidualization in both the gravid and pseudopregnant uterus, suggesting the effect on decidualization was independent of the conceptus. This included a suppression of endometrial stroma cell proliferation and of key decidualization regulators, including COX2, BMP2 and WNT4. Collectively, these data demonstrate that maternal epinephrine exposure during early pregnancy impairs uterine decidualization and embryo development, underlying early pregnancy failure.
Topics: Adrenergic Agonists; Animals; Bone Morphogenetic Protein 2; Cell Proliferation; Cells, Cultured; Cyclooxygenase 2; Embryonic Development; Epinephrine; Female; Mice; Pregnancy; RNA, Messenger; Receptors, Adrenergic; Signal Transduction; Stromal Cells; Uterus; Wnt4 Protein
PubMed: 31520687
DOI: 10.1016/j.reprotox.2019.09.003 -
Reproduction in Domestic Animals =... Dec 2022Anti-Müllerian hormone (AMH), known for its role during foetal sexual differentiation, is secreted by the Sertoli cells in males and the granulosa cells in females...
Anti-Müllerian hormone (AMH), known for its role during foetal sexual differentiation, is secreted by the Sertoli cells in males and the granulosa cells in females during post-natal life. As serum AMH concentrations correlate with follicle numbers, AMH is utilized as a marker of ovarian reserve in many species. In dogs and cats, AMH is used as a diagnostic tool to determine spay or neuter status. In the available literature, no research regarding serum AMH levels in rabbits has been published yet. The objectives of the present study were to (1) measure serum AMH concentrations in female rabbits and investigate the value of AMH as a diagnostic tool to differentiate between spayed and intact does and (2) relate measured AMH levels to pseudopregnancy and ovarian follicle numbers. For AMH measurement, serum samples were obtained from sexually intact (n = 64) and spayed (n = 22) female rabbits. Spayed does were of various breeds; intact rabbits were Zika hybrid rabbits. In the intact does, AMH measurement was complemented by determination of progesterone levels, gynaecological examination and histopathological evaluation of the uterus and ovaries, including follicle counts. Serum AMH and progesterone concentrations were measured using a human-based chemiluminescence immunoassay (CLIA) and an enzyme-linked fluorescence assay (ELFA), respectively. Depending on progesterone levels, sexually intact does were classified into follicular (n = 52) or luteal phase (n = 12). Median serum AMH levels were 1.53 ng/ml (range 0.77-3.36 ng/ml) in intact and 0.06 ng/ml (range ≤0.01-0.23 ng/ml) in spayed does. AMH concentrations between the intact and spayed rabbits differed significantly and did not overlap (p < .001). Receiver operating characteristic (ROC) curve analysis yielded a sensitivity and specificity of 100% for a cut-off level of 0.50 ng/ml. Follicular or luteal phase had no significant influence on measured AMH levels (t = 0.061, df = 62, p = .951). While the number of secondary follicles correlated significantly with AMH concentrations (r = 0.410, p = .001), the number of primary or antral follicles did not (r = 0.241, p = .055 and r = 0.137, p = .281, respectively). In conclusion, a single determination of serum AMH concentrations was adequate to distinguish spayed from intact female rabbits. Among sexually intact individuals, whether does were in follicular or luteal phase had no significant influence on measured serum AMH concentrations. The relationship between small growing follicles and AMH levels as described in other species could be partially confirmed, as secondary follicles correlated significantly with AMH.
Topics: Animals; Female; Male; Pregnancy; Rabbits; Anti-Mullerian Hormone; Ovarian Follicle; Progesterone; Pseudopregnancy
PubMed: 36052807
DOI: 10.1111/rda.14240 -
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 -
Open Veterinary Journal 2021Fibroadenomatous changes (FAC) of the mammary gland in cats represents a benign, progesterone-associated fibroglandular proliferation of one or more mammary glands that...
BACKGROUND
Fibroadenomatous changes (FAC) of the mammary gland in cats represents a benign, progesterone-associated fibroglandular proliferation of one or more mammary glands that may occur in intact female cats at the time of puberty, during pregnancy or pseudopregnancy, or in female and male cats of any age under progestin treatment. Nowadays, the elective treatment of FAC is based on the progesterone antagonist aglepristone. This study aimed to report the treatment of FAC with a combination of drugs designed to preserve mammary gland integrity, even in pregnant cats.
CASE DESCRIPTION
Eight sexually intact female cats with FAC showed mammary glands that were symmetrically enlarged and inflamed in all cases, and the skin was ulcerated in six cats. Four cats were on days 25-32 of pregnancy at presentation. Non-pregnant cats were treated with aglepristone and with a dietary supplement containing maltodextrin and bromelain. The mammary glands were massaged daily with an emollient gel. If the gland was inflamed or ulcerated, broad-spectrum antimicrobial, and anti-inflammatory treatments were given, and the ulcers were treated topically with a hypericum and neem-based cream. Two of the four pregnant cats were treated with the same therapeutic schedule plus cloprostenol to facilitate uterine emptying. Two pregnant cats underwent the same protocol except for aglepristone, which was not administered to safeguard the litter and see if the adjuvant therapy worked independently. At term, they delivered four and three kittens, respectively, that were normally nursed and weaned after 40 days. In all the studied cases, the mammary gland reduced in size 2-3 weeks after the start of the treatment and completely remitted after 4-5 weeks.
CONCLUSION
This case series encourages adjuvant therapy in the course of FAC to preserve mammary gland integrity and functionality. Exploiting the natural decline of progesterone at the end of pregnancy (or pseudopregnancy), the therapy may also be used without aglepristone, when its use has other limitations.
Topics: Animals; Cats; Conservative Treatment; Female; Male; Pregnancy; Progesterone; Uterus
PubMed: 35070864
DOI: 10.5455/OVJ.2021.v11.i4.19 -
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 -
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 -
Zoo Biology Mar 2022Despite decades of reproductive research on the giant panda (Ailuropoda melanoleuca), the post-ovulatory phase continues to confound zoologists in conservation and...
Despite decades of reproductive research on the giant panda (Ailuropoda melanoleuca), the post-ovulatory phase continues to confound zoologists in conservation and breeding centers around the world, often resulting in significant investments of time and resources without reproductive success. The purpose of this project was to document and compare post-ovulatory characteristics during a non-productive and productive breeding in the same individual in consecutive years. A multidisciplinary approach was used to monitor the visiting female giant panda at the Toronto Zoo through the luteal phase of her first two full reproductive cycles in 2014 and 2015. Monitoring occurred via urine-endocrine analysis, weekly ultrasound examinations, and continuous behavioral observations. The 2014 reproductive cycle consisted of a pseudopregnancy, characterized by an extended luteal phase (241 days), the identification of endometrial edema and folding during ultrasound examinations, and a lack of strong association between behavior patterns and urinary progestagen secretion. The 2015 reproductive cycle included increased feeding time through the primary progestagen rise compared to the previous year, followed by simultaneous decrease in appetite and increases in inactivity, resting, sitting upright, and pre-partum-associated behaviors. These changes began 25 days before the birth of twins on Day 153 post-ovulation. Both fetuses were detected via ultrasound 15 days pre-partum. These results suggest that an absence of pre-partum behaviors, ultrasound evidence of endometrial edema without a fetus, and an extended luteal phase may be indicative of pseudopregnancy in giant pandas. Simultaneous monitoring of morphology, behavior, and urinary-endocrine profiles showed clear differences between successful and unsuccessful reproductive years.
Topics: Animals; Animals, Zoo; Edema; Female; Luteal Phase; Pregnancy; Reproduction; Ursidae
PubMed: 34672395
DOI: 10.1002/zoo.21655 -
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