scholarly journals 264.The effects of progesterone on endometrial angiogenesis in pregnant and ovariectomised mice

2004 ◽  
Vol 16 (9) ◽  
pp. 264
Author(s):  
L. M. Walter ◽  
P. A. W. Rogers ◽  
J. E. Girling

In mice, early pregnancy is associated with an increase in endometrial angiogenesis in preparation for the implanting embryo. The aims of this study were to quantify endometrial angiogenesis in pregnant mice and to investigate the role of progesterone in promoting endothelial cell (EC) proliferation in ovariectomised mice; we hypothesised that EC proliferation would increase with increasing plasma progesterone concentrations in pregnant mice and that progesterone would stimulate EC proliferation in ovariectomised mice, but only following oestrogen priming. Uterine tissue from CBA x C57 mice was collected on Days 1–4 of pregnancy (n�=�4–5/day) when circulating progesterone concentrations are increasing but before implantation occurs. Prior to dissection, mice were injected with BrdU enabling proliferating EC to be quantified and localised within blood vessels by CD31/BrdU double staining immunohistochemistry. There was a significant increase in proliferating EC (Kruskal-Wallis statistic (KW) = 17.1, P = 0.002) on Day 3 of pregnancy (Days 1 and 2, no proliferation; Day 3,126.6 � 45.6 proliferating EC/mm2 (mean � s.e.)), when plasma progesterone also began to increase (as measured by radioimmunoassay). To determine if the EC proliferation was due to progesterone, a second experiment was performed on ovariectomised mice. One group of mice (n = 6) were treated with a single injection of 100 ng of estradiol on day eight after ovariectomy, followed by a day with no treatment and three consecutive daily injections of 1 mg progesterone. Other groups were treated with either the vehicle (n = 5), estradiol (n = 4) or progesterone (n = 5) injections only. All groups were dissected following BrdU injection on Day 13 following ovariectomy. Unexpectedly, mice treated with progesterone only had the highest amount of EC proliferation (114.7 � 30.9 proliferating EC/mm2); oestrogen priming was not required and actually significantly reduced progesterone induced EC proliferation (44.8 � 15.5 proliferating EC/mm2; KW = 13.8, P = 0.008). We are currently investigating the interaction between progesterone and VEGF using immunohistochemistry and inhibition studies.


Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 765-777 ◽  
Author(s):  
Lisa M Walter ◽  
Peter A W Rogers ◽  
Jane E Girling

The role of progesterone (and oestrogen) in endometrial angiogenesis remains controversial. The aims of this study were to quantify endometrial angiogenesis in pregnant mice and to investigate the role of progesterone in promoting endothelial cell proliferation in ovariectomized mice. Uteri were collected on days 1 to 4 of pregnancy when circulating progesterone concentrations were increasing, prior to implantation. Before dissection, mice were injected with bromodeoxyuridine (BrdU) enabling proliferating endothelial cells to be quantified with CD31/BrdU double-immunohistochemistry. There was a significant increase in proliferating endothelial cells on day 3 of pregnancy when plasma progesterone also increased. To determine if this endothelial cell proliferation was due to progesterone, an experiment was performed on ovariectomised mice. One group was treated with a single oestradiol injection on day 8 after ovariectomy, followed by a no-treatment day and three consecutive daily injections of progesterone. Other groups were treated with either the vehicle, oestradiol or progesterone injections only; all were dissected on day 13 following ovariectomy. Unexpectedly, mice treated with progesterone-only had the highest amount of endothelial cell proliferation and oestrogen priming was found to significantly reduce this progesterone-induced endothelial cell proliferation. To determine if this proliferation is mediated by vascular endothelial growth factor (VEGF), a further experiment in which VEGF anti-serum was administered concurrently with the progesterone injections was performed. Endothelial cell proliferation was reduced but not abolished suggesting progesterone-induced endometrial angiogenesis is only partly mediated by VEGF. Results indicate that oestrogen priming is not required for progesterone to stimulate endometrial endothelial cell proliferation and that oestrogen inhibits progesterone-induced angiogenesis in ovariectomised mice.



2006 ◽  
Vol 54 (3) ◽  
pp. 211 ◽  
Author(s):  
Y. P. Cruz ◽  
H. Morton ◽  
A. C. Cavanagh ◽  
L. Selwood ◽  
S. D. Wilson ◽  
...  

Maternal recognition of pregnancy in marsupials occurs in more subtle ways than it does in eutherians. For instance, unlike in eutherians, the plasma progesterone profiles of pregnant and non-pregnant animals are similar during the luteal phase. It is typically during the brief luteal phase that both gestation and parturition occur in marsupials. Yet histological and physiological changes have been documented between gravid and non-gravid uteri in certain monovular marsupials and between pregnant and non-pregnant animals in polyovular marsupials. Early pregnancy factor (EPF), a 10.8-kDa serum protein known to be homologous to chaperonin 10, is associated with maternal immunosuppression, embryonic development and pregnancy in eutherian mammals. It has been reported in two Australian marsupials: the dasyurid Sminthopsis macroura and the phalangerid Trichosurus vulpecula. This paper documents its occurrence in the New World didelphid Monodelphis domestica. EPF is detectable by rosette inhibition assay in the peripheral circulation of pregnant but not of non-pregnant or pseudopregnant animals. Our work focuses on the embryo–maternal signalling role of EPF during pregnancy. Because progesterone-driven changes are similar in pregnant and non-pregnant marsupials, these animals are an excellent laboratory model in which to investigate the role of EPF in orchestrating the physiological changes necessary to sustain pregnancy.



1969 ◽  
Vol 43 (2) ◽  
pp. 225-235 ◽  
Author(s):  
B. M. BINDON

SUMMARY The optimum conditions for delay of implantation by hypophysectomy and neurodepressive agents are described. Hypophysectomy on day 1 without hormone replacement was followed by retarded development and subsequent degeneration of zygotes. Viability of blastocysts was maintained under these conditions by a single injection of a long-acting progestagen on day 1. Hypophysectomy at intervals beginning late on day 3 indicated that implantation is initiated by pituitary activity in the several hours around midnight of this day. In animals induced to ovulate and copulate by exogenous gonadotrophin injections, the corresponding time of pituitary activity was delayed by approximately 8 hr. This delay could not be explained solely on the basis of altered times of ovulation. It is evident that the events of early pregnancy do not follow the normal physiological pattern under these conditions, and caution should be exercised in utilizing such animals. Of five neurodepressive agents examined, only trifluoperazine effectively delayed implantation. The effect of this substance injected at various times on day 3 of pregnancy suggests that implantation in the mouse is initiated by neurally regulated pituitary activity between 16.00 and 24.00 hr. on this day. Comparison with the mechanism of ovulation indicates that ovulation and implantation are regulated by separate hypothalamic-pituitary events, one peculiar to the oestrous cycle, the other to early pregnancy.



2005 ◽  
Vol 17 (9) ◽  
pp. 112
Author(s):  
L. M. Walter ◽  
P. A. W. Rogers ◽  
J. E. Girling

Previous studies have suggested that progesterone stimulates stromal cell (SC) proliferation in the mouse endometrium1. However, these studies have not differentiated endothelial cells (EC) from other SC. In this study, we investigated the effects of progesterone on cellular proliferation in ovariectomised mouse endometrium. We hypothesised that progesterone would stimulate both SC and EC proliferation. One group of CBA × C57 mice (n = 6) were treated with a single injection of 100 ng of estradiol on day eight following ovariectomy, followed by a day with no treatment and three consecutive daily injections of 1 mg progesterone. Other groups were treated with either the vehicle (n = 5), estradiol (n = 4) or progesterone (n = 5) injections only. All groups were dissected on day 13 after ovariectomy, 4 h following a BrdU injection. CD31/BrdU double staining immunohistochemistry allowed proliferating EC to be differentiated from proliferating SC. Mice treated with progesterone only had significantly higher EC proliferation in comparison to females treated with progesterone following oestrogen priming (P = 0.05) or vehicle only (P = 0.01) (progesterone only: median=97.3 proliferating EC (PEC)/mm2 [range = 60.8–203.4]; oestrogen plus progesterone: 41.0 PEC/mm2 [8.9–86.9]; vehicle only: 0.0 PEC/mm2 [0.0–3.1]). Unexpectedly, there was no significant difference in SC proliferation among the treatment groups (progesterone only: 50.1 PSC/mm2 [39.2–102.6]; oestrogen plus progesterone: 46.1 PSC/mm2 [12.6–120.8]; vehicle only: 44.8 PSC/mm2 [17.3–68.4]). To determine if VEGF had a role in the progesterone-induced EC proliferation, the previous experiment was repeated with the inclusion of mice treated with VEGF anti-serum. The addition of VEGF anti-serum significantly inhibited progesterone-induced EC proliferation (46.8 PEC/mm2 [38.9–128.0]; P = 0.04], but had no effect on SC proliferation (P = 0.3). These results demonstrate that progesterone stimulates endometrial EC proliferation, but not SC proliferation as reported by earlier studies1. Studies are currently underway to further investigate the role of VEGF in mediating progesterone effects on endometrial EC. (1)Clarke, C.L. and Sutherland, R.L. (1990) Endocrine Reviews 11, 266–301.



1981 ◽  
Vol 21 (113) ◽  
pp. 562 ◽  
Author(s):  
FD Brien ◽  
IA Cumming ◽  
IJ Clarke ◽  
CS Cocks

Eighty-eight maiden and 125 mature Merino ewes were grazed on green irrigated pasture or given dry hay on a fallow area with or without a lupin grain supplement just before and during mating. Progesterone concentrations in peripheral plasma were measured at 12 d after coitus. Progesterone concentration was lower (2.27 vs 2.87 ng/ml, P < 0.001 ) when lupins were fed, and maiden ewes had higher progesterone concentrations than mature ewes (2.75 vs 2.36 ng/ml, P < 0.05). Pregnant ewes had higher progesterone concentrations than non-pregnant ewes (2.77 vs 2.36 ng/ml, P < 0.05), and ewes with two ovulations had higher progesterone concentrations than ewes with a single ovulation (3.13 vs 2.08 ng/ml, P < 0.001). There was an interaction between pasture type and lupin supplement, with lupins depressing progesterone level more on green irrigated pasture (lupins 2.11 ng/ml, no lupins 3.00 ng/ml, P < 0.05) than on dry pasture (lupins 2.45 ng/ml, no lupins 2.74 ng/ml, P < 0.05). The results confirm that a high plane of nutrition at mating lowers progesterone levels in plasma and suggest that this may be a factor in the increase in embryo deaths when ewes are fed lupin grain supplements.



1970 ◽  
Vol 65 (3_Suppl) ◽  
pp. S5-S32 ◽  
Author(s):  
K. Loewit

ABSTRACT The role of luteinizing hormone (LH) for the maintenance of pregnancy, parturition and lactation was investigated by immunological and histochemical methods in the rat. Neutralisation of endogenous rat-LH with Rabbit-Anti-Bovine-LH-Serum (selective hypophysectomy) from days 7-12 of pregnancy resulted in reabsorption of the foetuses and the reappearance of strong 20α-hydroxysteroid-dehydrogenase (20α-OHSD) activity in the corpora lutea (CL) of pregnancy, which normally show no such activity at that time. This effect could be prevented in part by concurrent pregnenolone administration and fully by progesterone, but was not influenced by oestrogen or prolactin. It is concluded that in early pregnancy LH is the main luteotrophic hormone in the rat even though prolactin might act synergistically with it. Antiserum treatment after the 12th day of gestation had no influence on the state or duration of pregnancy or on parturition. LH-injections during the first half of pregnancy had no luteolytic effects i. e. they did not activate 20α-OHSD activity. After day 16 they advanced the reappearance of the enzyme, but delayed parturition or resulted in stillbirths. Neither LH nor antiserum seemed to alter lactation. Since progesterone prevented both the termination of pregnancy and the recurrence of 20α-OHSD activity, it should have some regulatory properties on the enzyme. It is discussed whether the gonadotrophin-dependent progesterone level could regulate the 20α-OHSD activity rather than result from it.



Reproduction ◽  
1971 ◽  
Vol 24 (1) ◽  
pp. 146-a-147 ◽  
Author(s):  
I. Cumming ◽  
B. Mole ◽  
J Obst ◽  
M. Blockey ◽  
C. Winfield ◽  
...  


Reproduction ◽  
2000 ◽  
pp. 387-395 ◽  
Author(s):  
KJ Demmers ◽  
HN Jabbour ◽  
DW Deakin ◽  
AP Flint

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.



GYNECOLOGY ◽  
2019 ◽  
Vol 21 (3) ◽  
pp. 9-16
Author(s):  
Nataly I Frolova ◽  
Tatiana E Belokrinitskaya

Background. Miscarriage is a common complication in early pregnancy. Current studies have shown a higher prevalence of miscarriage, ranging from 10 to 20%. The review is devoted to modern concepts of etiology and pathogenesis of early pregnancy losses. Aim. Assess the role of epigenetic factors and molecular-genetic markers in the pathogenesis and prediction of early pregnancy losses Materials and methods. In order to write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLibrary, etc.) for the last 10-15 years. Relevant articles from the peer-reviewed literature and clinical practice guidelines were included. Results. Many recent studies have proved the contribution of various epigenetic factors to the pathogenesis of spontaneous miscarriages, and the molecular-genetic determination such kinds of pregnancy complication has been confirmed. Conclusion. The miscarriage in early gestation is driven by combined impact of epigenetic and molecular-genetic factors, as well as the presence of intergenic interactions. It is may lead to deterioration of physiological functions, and maternal pathologenic pathways could be changed as during her periconceptional period as so during the pregnancy.





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