In vivo myometrial activity during early pregnancy and pseudopregnancy in the rat

Video-laparoscopic studies in early pregnant and pseudopregnant rats showed large changes in frequency, direction of propagation and nature of myometrial contractions. Day 2 patterns of activity were essentially the same as in unmated animals at the equivalent stage of the cycle. From Days 3 to 5 there was a large increase in longitudinal and circular contractions propagating towards the oviduct, circular contractions making the greatest contribution. This circular activity may be important in retaining and spacing embryos. Circular contractions propagating towards the cervix showed smaller increases and there was a transient diminution in the frequency of longitudinal contractions in this direction on Day 5. In pregnant rats, the frequency of discrete contractions declined on Days 6-7. However, circular tone appeared to be increased and uteri showed dramatic twisting and curling, apparently due to resistance to the shortening imposed by longitudinal contractions. None of the major changes in activity appeared to be caused by embryos, because they were seen in pseudopregnant rats and, after embryo implantation, in both horns of unilaterally pregnant rats. The earliest divergence from the activity patterns of unmated rats occurred when progesterone levels first increased significantly above those of the undisturbed oestrous cycle, suggesting that progesterone has a major influence on myometrial activity. The complexity of the changes in activity raises questions about other regulatory factors, particularly in regard to coordination between the circular and longitudinal muscle layers. Anomalous results from pregnant, unilaterally pregnant, and pseudopregnant animals on Day 7 suggested that embryos exert systemic effects on myometrial activity.

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YY1 and RTCB in mouse uterine decidualization and embryo implantation

Reproduction ◽

10.1530/rep-21-0281 ◽

2021 ◽

Author(s):

Ran Li ◽

Xiao-Tong Song ◽

Si-Wei Guo ◽

Na Zhao ◽

Mei He ◽

...

Keyword(s):

Early Pregnancy ◽

Embryo Implantation ◽

Mrna Splicing ◽

Proximal Promoter ◽

Mouse Uterus ◽

Rna Ligase ◽

Xbp1 Mrna ◽

Transcription Factor Yy1

As a multifunctional transcription factor, YY1 regulates the expression of many genes essential for early embryonic development. RTCB is an RNA ligase that plays a role in tRNA maturation and Xbp1 mRNA splicing. YY1 can bind in vitro to the response element in the proximal promoter of Rtcb and regulate Rtcb promoter activity. However, the in vivo regulation and whether these two genes are involved in the mother-fetal dialogue during early pregnancy remain unclear. In this study, we validated that YY1 bound in vivo to the proximal promoter of Rtcb in mouse uterus of early pregnancy. Moreover, via building a variety of animal models, our study suggested that both YY1 and RTCB might play a role in mouse uterus decidualization and embryo implantation during early pregnancy.

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Effect of oestrous cycle and early pregnancy on uterine production and expression of immune regulatory factors in gilts

Animal Reproduction Science ◽

10.1016/j.anireprosci.2003.08.008 ◽

2004 ◽

Vol 81 (1-2) ◽

pp. 137-149 ◽

Cited By ~ 8

Author(s):

V Chabot ◽

R.D Lambert ◽

J.-P Laforest ◽

S St-Jacques ◽

J.J Matte ◽

...

Keyword(s):

Early Pregnancy ◽

Oestrous Cycle ◽

Regulatory Factors

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Endometrial pyruvate kinase M2 is essential for decidualization during early pregnancy

Journal of Endocrinology ◽

10.1530/joe-19-0553 ◽

2020 ◽

Vol 245 (3) ◽

pp. 357-368 ◽

Cited By ~ 2

Author(s):

Yan Su ◽

Sujuan Guo ◽

Chunyan Liu ◽

Na Li ◽

Shuang Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Pyruvate Kinase ◽

Early Pregnancy ◽

Stromal Cells ◽

Embryo Implantation ◽

Pyruvate Kinase M2 ◽

Ishikawa Cells ◽

Implantation Sites

Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis process which catalyzes phosphoenolpyruvic acid into pyruvate. However, little is known regarding the role of PKM2 during endometrial decidualization. In this study, PKM2 was found to be mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in the decidual zone after embryo implantation. PKM2 was dramatically increased with the onset of decidualization. Upon further exploration, PKM2 was found to be more highly expressed at the implantation sites than at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualization both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced, and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

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227.An inhibitor of leukemia inhibitory factor signalling blocks embryo implantation in the mouse

Reproduction Fertility and Development ◽

10.1071/srb04abs227 ◽

2004 ◽

Vol 16 (9) ◽

pp. 227

Author(s):

E. Dimitriadis ◽

C. Stoikos ◽

M. Baca ◽

W. Fairlie ◽

A. D. Uboldi ◽

...

Keyword(s):

Early Pregnancy ◽

Leukemia Inhibitory Factor ◽

Embryo Implantation ◽

Uterine Horn ◽

Inhibitory Factor ◽

Luminal Epithelium ◽

Pregnant Uterus ◽

Implantation Sites ◽

Post Implantation

Embryo implantation is a critical step in the establishment of pregnancy. Endometrial leukemia inhibitory factor (LIF) is essential for embryo implantation in the mouse (1). Uterine LIF is expressed in the luminal epithelium on Day 3 of pregnancy (D3) (D0�=�day of plug detection) and signals via activation of signal transducer and activator of transcription (Stat) 3 (2). We examined the effect of a novel LIF signalling inhibitor on the phosphorylation (p) of Stat3 during early pregnancy and on embryo implantation in the mouse. We injected LIF inhibitor into one uterine horn and PBS into the other uterine horn of the mouse at D3 and examined the effect on pStat3 immunostaining in the luminal epithelium between 30 and 360�min later. We found no immunoreactive pStat3 in luminal epithelium following treatment with LIF inhibitor at 60 and 90�min but variable staining at other time points. The PBS-treated uterine horn showed intense immunostaining at all times. LIF inhibitor (1mg/kg body weight per day) or PBS was administered to mice (a) subcutaneously, (b) intraperitoneally, at 8-hourly intervals for 3�days from D2, or (c) continuously into the peritoneal cavity via Alzet pumps from D2. No effect was seen on implantation at D6. When LIF antagonist (3.5mg/kg/day) or PBS were administered by Alzet pumps from D2 together with ip injections, 4-hourly from D3 for 36�h, there were no implantation sites in the uteri of treated mice (n�=�5) while the control mice (n�=�4) had 3.6��0.5�sites (P�<�0.001). Histologically, the uteri of the treated mice resembled non-pregnant uterus, while the control uterus resembled post-implantation uterus. The results demonstrate that treatment of mice during early pregnancy with a novel LIF inhibitor blocks LIF action in vivo and embryo implantation. This knowledge is important for development of novel contraceptives. (1) Stewart, C. L., Kaspar, P., Brunet, L. J., Bhatt, H., Gadi, I., Kontgen, F., Abbondanzo, S. J. (1992) Nature 359, 76–79. (2) Cheng, J. G., Chen, J. R., Hernandez, L., Alvord, W. G., Stewart, C. L. (2001) Proc. Natl Acad. Sci. USA 98, 8680–8685.

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Uterine expression of implantation serine proteinase 2 during the implantation period and in vivo inhibitory effect of its antibody on embryo implantation in mice

Reproduction Fertility and Development ◽

10.1071/rd03102 ◽

2004 ◽

Vol 16 (3) ◽

pp. 379 ◽

Cited By ~ 15

Author(s):

Z. P. Huang ◽

H. Yu ◽

Z. M. Yang ◽

W. X. Shen ◽

J. Wang ◽

...

Keyword(s):

Protein Expression ◽

Early Pregnancy ◽

Embryo Implantation ◽

Serine Proteinase ◽

Inhibitory Effect ◽

Uterine Lumen ◽

Rabbit Igg ◽

The Mean ◽

Implantation Period

The aim of the present study was to examine the uterine expression pattern of implantation serine proteinase 2 (ISP2) protein during early pregnancy in mice and the effects of anti-ISP2 antibody on embryo implantation. Expression of ISP2 protein was found to be specifically up-regulated in mouse uterine endometrial glands following the initiation of embryo implantation. Similarly, ISP2 protein expression was observed during pseudopregnancy, indicating that its expression is not embryo dependent. In other experiments, rabbit anti-ISP2 IgG was infused into the mouse uterine lumen on Day 3 or 4 of pregnancy to examine its effects on embryo implantation, whereas vehicle (saline) or unspecific rabbit IgG served as controls. The mean number of implanted embryos from anti-ISP2-IgG-treated mice was significantly lower than that from control mice. These results suggest that ISP2 may play an important role during embryo implantation.

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Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats

Reproduction Fertility and Development ◽

10.1071/rd9920161 ◽

1992 ◽

Vol 4 (2) ◽

pp. 161 ◽

Cited By ~ 2

Author(s):

LH Crane ◽

L Martin

Keyword(s):

Early Pregnancy ◽

Pacemaker Activity ◽

Long Term Effects ◽

Embryo Abortion ◽

Pregnant Rats ◽

Video Laparoscopy ◽

Antagonist Ru486 ◽

Progesterone Antagonist

Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix.

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Expression and function of Pdcd4 in mouse endometrium during early pregnancy

Reproduction ◽

10.1530/rep-17-0787 ◽

2018 ◽

Vol 155 (4) ◽

pp. 393-402 ◽

Cited By ~ 5

Author(s):

Yue Zhang ◽

Mingyun Ni ◽

Na Liu ◽

Yongjiang Zhou ◽

Xuemei Chen ◽

...

Keyword(s):

Early Pregnancy ◽

Quantitative Polymerase Chain Reaction ◽

Embryo Implantation ◽

Complex Process ◽

Programmed Cell Death 4 ◽

Implantation Sites ◽

And Function

Embryo implantation is a complex process involving synchronised crosstalk between a receptive endometrium and functional blastocysts. Apoptosis plays an important role in this process as well as in the maintenance of pregnancy. In this study, we analysed the expression pattern of programmed cell death 4 (Pdcd4), a gene associated with apoptosis in the mouse endometrium, during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, in situ hybridisation, Western blotting and immunohistochemistry. The results showed that Pdcd4 was increased along with days of pregnancy and significantly reduced at implantation sites (IS) from day 5 of pregnancy (D5). The level of Pdcd4 at IS was substantially lower than that at interimplantation sites (IIS) on D6 and D7. In addition, Pdcd4 expression in the endometrium was reduced in response to artificially induced decidualisation in vivo and in vitro. Downregulation of Pdcd4 gene expression in cultured primary stromal cells promoted decidualisation, while upregulation inhibited the decidualisation process by increasing apoptosis. These results demonstrate that Pdcd4 is involved in stromal cell decidualisation by mediating apoptosis and therefore plays a role in embryo implantation in mice.

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Testosterone Decreases the Number of Implanting Embryos, Expression of Pinopode and L-selectin Ligand (MECA-79) in the Endometrium of Early Pregnant Rats

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17072293 ◽

2020 ◽

Vol 17 (7) ◽

pp. 2293

Author(s):

Mohd Helmy Mokhtar ◽

Nelli Giribabu ◽

Naguib Salleh

Keyword(s):

Adverse Effect ◽

Early Pregnancy ◽

Structural Changes ◽

Embryo Implantation ◽

Normal Endometrium ◽

Pregnant Rats ◽

Selectin Ligand ◽

Implantation Sites

Testosterone could have adverse effect on fertility. In this study, we hypothesized that this hormone could reduce the number of embryo implantations via affecting the normal endometrium ultrastructure and expression of endometrial proteins involved in implantation. Therefore, the aims were to identify these adverse testosterone effects. Methods: Intact pregnant rats were given 250 or 500 µg/kg/day testosterone for three days, beginning from day 1 of pregnancy. Rats were euthanized either at day 4 to analyze the ultra-structural changes in the endometrium and expression and distribution of MECA-79 protein, or at day 6 to determine the number of implantation sites. Results: Administration of 500 µg/kg/day testosterone suppresses endometrial pinopodes development and down-regulates expression and distribution of MECA-79 protein in the uterus. In addition, the number of implantation sites were markedly decreased. Conclusions: Changes in endometrial ultrastructure and expression of implantation protein in the endometrium in early pregnancy period could be the reason for failure of embryo implantation under testosterone influence.

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