-
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 -
The Journal of Reproduction and... Aug 2016The induction of pseudopregnancy by the exogenous administration of estradiol dipropionate (EDP) was investigated in cyclic Microminipigs (MMpigs) and the effects of...
The induction of pseudopregnancy by the exogenous administration of estradiol dipropionate (EDP) was investigated in cyclic Microminipigs (MMpigs) and the effects of exogenous administration of prostaglandin (PG) F2α on estrus exhibition were assessed in pseudopregnant MMpigs. In experiment 1, ovariectomized MMpigs were given a single intramuscular injection of 0.5, 1.5, or 2.5 mg of EDP. The estradiol-17β level at each of these doses was significantly higher 1 to 3 days after EDP administration than on the day of the injection. In experiment 2, animals were given 1.5 mg of EDP once at 9 to 12 days after the end of estrus (D0) and then no (1.5 mg × 1 group), one (D0 and D4; 1.5 mg × 2 group), or two (D0, D4 and D7; 1.5 mg × 3 group) additional treatments. The pseudopregnancy rate was significantly higher in the 1.5 mg × 3 than in the 1.5 mg × 1 group. In experiment 3, PGF2α was administered twice between 26 and 28 days after EDP treatment to five pseudopregnant gilts with a 24-h interval between the two injections. Estrus after PGF2α treatment and LH surge were observed in 100% and 80% pseudopregnant MMpigs, respectively. The interval from the day of the first PGF2α treatment to the onset of estrus was 6.5 ± 0.2 days. These results indicate that multiple EDP treatments are required for induction of pseudopregnancy in MMpigs and estrus exhibition can be controlled in MMpigs by treatment with EDP and PGF2α.
Topics: Animals; Dinoprost; Estradiol; Estrus Synchronization; Female; Ovariectomy; Pseudopregnancy; Swine; Swine, Miniature
PubMed: 27151362
DOI: 10.1262/jrd.2015-169 -
Journal of the American Veterinary... Apr 2002To assess the efficacy and safety of 2 protocols using bromocriptine mesylate and prostaglandins to terminate unwanted pregnancy in bitches. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To assess the efficacy and safety of 2 protocols using bromocriptine mesylate and prostaglandins to terminate unwanted pregnancy in bitches.
DESIGN
Prospective randomized single-blind controlled study.
ANIMALS
34 crossbred and purebred bitches referred for possible pregnancy termination. Seven additional pregnant bitches were used as controls.
PROCEDURE
Pregnancy was assessed by ultrasonographic examination from day 25 after mating in all bitches. Of the 34 bitches, 25 were pregnant and were randomly allocated to a treatment group. Group-1 dogs (n = 12) received a combination of increasing amounts of bromocriptine mesylate (15 to 30 microg/kg [6.8 to 13.6 microg/lb], p.o., q 12 h) and dinoprost tromethamine (0.1 to 0.2 mg/kg [0.045 to 0.09 mg/lb], s.c., q 24 h). Group-2 dogs (n =13) received a combination of increasing amounts of bromocriptine mesylate (the same schedule as group-1 dogs) and cloprostenol sodium (1 microg/kg [0.45 microg/lb], s.c., q 48 h). Both groups were treated until pregnancy termination. Results-Treatment success was 100% in both groups. Days of treatment required for pregnancy termination did not significantly differ between groups (5.0 +/- 0.6 vs 3.7 +/- 0.6 days, group-1 and group-2 dogs, respectively) although adverse effects only developed in group-1 dogs. At the end of the protocols, pseudopregnancy was observed in 3 of 12 and 6 of 13 group-1 and group-2 dogs, respectively. Pregnancy termination was followed by a mucoid sanguineous vulvar discharge for 3 to 10 days.
CONCLUSIONS AND CLINICAL RELEVANCE
Results of this study indicate that protocols that combine the use of bromocriptine mesylate and prostaglandins for the termination of unwanted pregnancy in bitches are efficient and safe. The use of bromocriptine mesylate and cloprostenol had the best results and could be easily used on an outpatient basis.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Abortion, Veterinary; Animals; Bromocriptine; Cloprostenol; Dinoprost; Dogs; Female; Pregnancy; Prospective Studies; Prostaglandins; Safety; Single-Blind Method; Treatment Outcome
PubMed: 12420779
DOI: 10.2460/javma.2002.220.1017 -
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 -
Journal of Applied Biomechanics Aug 2016During pregnancy, the female body experiences structural changes, such as weight gain. As pregnancy advances, most of the additional mass is concentrated anteriorly on...
During pregnancy, the female body experiences structural changes, such as weight gain. As pregnancy advances, most of the additional mass is concentrated anteriorly on the lower trunk. The purpose of this study is to analyze kinematic and kinetic changes when load is added anteriorly to the trunk, simulating a physical change experienced during pregnancy. Twenty healthy females walked on a treadmill while wearing a custom made pseudo-pregnancy sac (1 kg) under 3 load conditions: sac-only condition, 10-lb condition (4.535 kg added anteriorly), and 20-lb condition (9.07 kg added anteriorly), used to simulate pregnancy in the second trimester and at full-term pregnancy, respectively. The increase in anterior mass resulted in kinematic changes at the knee, hip, pelvis, and trunk in the sagittal and frontal planes. In addition, ankle, knee, and hip joint moments normalized to baseline mass increased with increased load; however, these moments decreased when normalized to total mass. These kinematic and kinetic changes may suggest that women modify gait biomechanics to reduce the effect of added load. Furthermore, the increase in joint moments increases stress on the musculoskeletal system and may contribute to musculoskeletal pain.
Topics: Biomechanical Phenomena; Female; Gait; Humans; Lower Extremity; Pregnancy; Thorax; Weight Gain; Young Adult
PubMed: 26958743
DOI: 10.1123/jab.2015-0178 -
Reproductive Biology and Endocrinology... Aug 2009During the estrous cycle, the rat uterine endometrium undergoes many changes such as cell proliferation and apoptosis. If implantation occurs, stromal cells...
Transforming growth factor beta isoforms regulation of Akt activity and XIAP levels in rat endometrium during estrous cycle, in a model of pseudopregnancy and in cultured decidual cells.
BACKGROUND
During the estrous cycle, the rat uterine endometrium undergoes many changes such as cell proliferation and apoptosis. If implantation occurs, stromal cells differentiate into decidual cells and near the end of pregnancy, a second wave of apoptosis occurs. This process called decidual regression, is tightly regulated as is it crucial for successful pregnancy. We have previously shown that TGF-beta1, TGF-beta2 and TGF-beta3 are expressed in the endometrium during decidual basalis regression, but although we had demonstrated that TGF- beta1 was involved in the regulation of apoptosis in decidual cells, the ability of TGF- beta2 and TGF-beta3 isoforms to trigger apoptotic mechanisms in these cells remains unknown. Moreover, we hypothesized that the TGF-betas were also present and regulated in the non-pregnant endometrium during the estrous cycle. The aim of the present study was to determine and compare the specific effect of each TGF-beta isoform in the regulation of apoptosis in sensitized endometrial stromal cells in vitro, and to investigate the regulation of TGF-beta isoforms in the endometrium during the estrous cycle in vivo.
METHODS
Rats with regular estrous cycle (4 days) were killed at different days of estrous cycle (diestrus, proestrus, estrus and metestrus). Pseudopregnancy was induced with sex steroids in ovariectomized rats and rats were killed at different days (days 1-9). Uteri were collected and either fixed for immunohistochemical staining (IHC) or processed for RT-PCR and Western analyses. For the in vitro part of the study, rats were ovariectomized and decidualization was induced using sex steroids. Endometrial stromal decidual cells were purified, cultured and treated with different concentrations of TGF-beta isoforms.
RESULTS
Our results showed that all three TGF-beta isoforms are present, but are localized differently in the endometrium during the estrous cycle and their expression is regulated differently during pseudopregnancy. In cultured stromal cells, we found that TGF-beta3 isoform induced Smad2 phosphorylation, indicating that the Smad pathway is activated by TGF-beta3 in these cells. Furthermore, TGF-beta2 and TGF-beta3 induced a dose-dependant increase of apoptosis in cultured stromal cells, as demonstrated by Hoechst nuclear staining. Noteworthy, TGF-beta2 and TGF-beta3 reduced the level of the anti-apoptotic XIAP protein, as well as the level of phosphorylated/active Akt, a well known survival protein, in a dose-dependent manner.
CONCLUSION
Those results suggest that TGF-beta might play an important role in the remodelling endometrium during the estrous cycle and in the regulation of apoptosis in rat decidual cells, in which inhibition of Akt survival pathway might be an important mechanism involved in the regulation of apoptosis.
Topics: Animals; Apoptosis; Cells, Cultured; Decidua; Endometrium; Estrous Cycle; Female; Pregnancy; Proto-Oncogene Proteins c-akt; Pseudopregnancy; Rats; Rats, Sprague-Dawley; Stromal Cells; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factor beta2; Transforming Growth Factor beta3; X-Linked Inhibitor of Apoptosis Protein
PubMed: 19656380
DOI: 10.1186/1477-7827-7-80 -
BMJ (Clinical Research Ed.) Dec 1992
Topics: Abortion, Induced; Abortion, Missed; Administration, Oral; Adult; Female; Humans; Mifepristone; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First
PubMed: 1486304
DOI: 10.1136/bmj.305.6866.1399 -
Biology of Reproduction Aug 2012Implantation failure is a major hurdle to a successful pregnancy. The high rate of postimplantation fetal loss in nonobese diabetic (NOD) mice is believed to be related...
Implantation failure is a major hurdle to a successful pregnancy. The high rate of postimplantation fetal loss in nonobese diabetic (NOD) mice is believed to be related to an abnormal decidual production of interferon (IFN)gamma. To address whether diabetes alters the natural events associated with successful implantation, certain morphological and molecular features of uterine receptivity in diabetic NOD (dNOD) mice were examined in normally mated pregnancy and in concanavalin A (ConA)-induced pseudopregnancy. As opposed to normoglycemic NOD (cNOD) mice, dNOD mice expressed retarded maturation of their uterine pinopodes and overexpressed MUC1 mucin at implantation sites (P < 0.001). Uterine production of leukemia inhibitory factor (LIF) and phosphorylation of uterine NFkappaBp65 and STAT3-Ty705 were found to be low (P < 0.01) during Day 4.5 postcoitum, whereas IFNgamma was aberrantly overexpressed. Loss of temporal regulation of progesterone receptor A (PR A) and PR B, together with aberrantly increased expression of the protein inhibitor of activated STAT-y (PIASy) (P < 0.01) and reduced recruitment (P < 0.01) of the latter to nuclear progesterone receptor sites were prominent features of decidualization failure occurring at peri-implantation in dNOD mice. In conclusion, the aberrant expression of endometrial IFNgamma in dNOD mice is associated with a nonreceptive endometrial milieu contributing to peri-implantation embryo loss in type 1 diabetes.
Topics: Abortion, Spontaneous; Animals; Concanavalin A; Diabetes Mellitus, Type 1; Embryo Implantation; Endometrium; Female; Interferon-gamma; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mucin-1; Pregnancy; Protein Inhibitors of Activated STAT; Receptors, Progesterone; STAT3 Transcription Factor; Transcription Factor RelA
PubMed: 22539679
DOI: 10.1095/biolreprod.112.100016 -
Biology of Reproduction Mar 2012A drop in mean arterial pressure (MAP) characterizes early, normal pregnancies of humans and of inbred mice, species with hemochorial placentation. Murine MAP, assessed...
A drop in mean arterial pressure (MAP) characterizes early, normal pregnancies of humans and of inbred mice, species with hemochorial placentation. Murine MAP, assessed by continuous radiotelemetry, falls from implantation to Gestation Day 9 (GD9) and then recovers. The change in the trajectory of mouse MAP after GD9 coincides with full maturity of the placenta and onset of its circulation. To identify whether these early gestational changes in hemodynamic function are conceptus and/or maternally regulated, pseudopregnancy (conceptus absent) with endometrial decidualization was established in radio transmitter-implanted, randomly bred CD1 mice. To avoid destabilization of MAP by anesthesia and surgery, decidualization was induced by transcervical infusion of concanavalin A-coated Sepharose beads 48 h after the female had copulated with a vasectomized male. In comparison to the postimplantation drop in MAP recorded in CD1 females mated by fertile males, pseudopregnancy MAP was stable to Gestation-Equivalent Day 10 in mice with confirmed endometrial decidualization at euthanasia. Thus, decidualization, with its accompanying pregnancy-like endocrine environment and uterine neoangiogensis and immune cell recruitment, is inadequate to depress early postimplantation MAP. These data suggest that the physiological modulation of early gestational MAP is not driven by maternal changes but is altered through conceptus-based mechanisms.
Topics: Animals; Blood Pressure; Concanavalin A; Decidua; Endometrium; Female; Fetus; Hemodynamics; Hypotension; Mice; Mice, Inbred ICR; Mice, Inbred Strains; Mitogens; Models, Animal; Pregnancy; Pregnancy, Animal
PubMed: 22156477
DOI: 10.1095/biolreprod.111.096958 -
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