308. FOLLISTATIN SPLICE VARIANTS FST288 AND FST315 INCREASE DURING EARLY MOUSE PREGNANCY: REGULATION BY PROGESTERONE?

2010 ◽  
Vol 22 (9) ◽  
pp. 108
Author(s):  
R. G. Craythorn ◽  
W. R. Winnall ◽  
M. P. Hedger ◽  
P. A. W. Rogers ◽  
D. M. De Kretser ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Early Pregnancy ◽  
Reproductive Tract ◽  
Splice Variants ◽  
Heparan Sulphate ◽  
Activin A ◽  
Female Reproductive Tract ◽  
Mouse Uterus ◽  
Rate Of Increase ◽  
Exogenous Progesterone

Follistatin acts by binding and neutralising the activity of activin-A, which has important regulatory roles in development, reproduction and inflammation. There are two isoforms of follistatin comprising 288 and 315 amino acids (FST288 and FST315), resulting from alternative gene splicing. FST288 binds spontaneously to heparan sulphate and is largely bound to cell surface proteoglycans. FST315 is the predominant circulating form and can only bind to heparan sulphate after binding activin-A. The regulation of these splice variants in the female reproductive tract have not been investigated in detail. In this study, our aim was to quantify the expression of FST288 and FST315 mRNA in the mouse uterus during early pregnancy (days 1–4, pre-implantation), and in response to exogenous oestradiol-17b (100 ng × single s.c. injection, dissection after 24 h) and progesterone (1 mg × three daily s.c. injections, dissection 24 h after last injection) in ovariectomised mice. Gene expression was analysed using quantitative RT-PCR. Primers amplifying a product from exon 5 to 6a (unique to FST288) or from exon 5 to 6b (unique to FST315) were used to discriminate the isoforms. In early pregnancy, expression of both FST288 and FST315 increased significantly (approximately 35-fold and 100-fold, respectively) on days 3–5, relative to days 1–2, corresponding with the increase in circulating progesterone levels that occurs at day 3. A significant increase in FST288 and FST315 mRNA expression (both approximately 35-fold) was also observed in ovariectomised mice in response to exogenous progesterone, but there was no increase in response to oestradiol-17β. In contrast to the similar rate of increase in response to exogenous progesterone, FST315 mRNA expression increased more rapidly than FS288 in early pregnancy, indicating that differential regulation of the two isoforms also occurs. We conclude that progesterone regulates both FST288 and FST315 mRNA expression during early pregnancy in the mouse uterus.

scholarly journals Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Reproductive Tract ◽  
Ovarian Function ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Female Reproductive Tract ◽  
Uterine Receptivity ◽  
Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

scholarly journals Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

2015 ◽  
Vol 112 (49) ◽  
pp. 15166-15171 ◽  
Author(s):  
Shannon D. Whirledge ◽  
Robert H. Oakley ◽  
Page H. Myers ◽  
John P. Lydon ◽  
Francesco DeMayo ◽  
...  
Keyword(s):  
Glucocorticoid Receptors ◽  
Reproductive Tract ◽  
Immune Cell ◽  
Steroid Receptors ◽  
Embryo Implantation ◽  
Female Reproductive Tract ◽  
Mouse Uterus ◽  
Glucocorticoid Signaling ◽  
Endocrine Organs

In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic–pituitary–adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions.

scholarly journals Chlamydia muridarum infection differentially changes smooth muscle contractility and responses to prostaglandins in uterus and cervix

2018 ◽  
Author(s):  
Jia Ming Lee ◽  
Jemma R. Mayall ◽  
Anne Chevalier ◽  
Dirk Van Helden ◽  
Jay C. Horvat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mrna Expression ◽  
Reproductive Tract ◽  
Uterine Horn ◽  
Female Reproductive Tract ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Contraction Amplitude ◽  
Chlamydia Muridarum ◽  
Reproductive Tract Infection

AbstractChlamydia trachomatis infection is a primary cause of reproductive tract diseases including chronic pelvic pain and infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activity of the uterus and the cervix in a Chlamydia muridarum (Cmu) mouse model of reproductive tract infection. Uterine or cervix smooth muscle contractility, responses to oxytocin or prostaglandins (PGF2α and PGE2) and mRNA expression of oxytocin and PG receptors were assessed 14 days post infection. Cmu infection did not affect the contractions of the uterine horn but significantly decreased the contraction amplitude of the cervix. Cmu infection did not alter the responses of uterine horn or cervix to oxytocin, however PGF2α induced contractions of the uterine horn, but not the cervix, were significantly increased following Cmu infection. PGE2 contraction amplitude in both the uterine horn and cervix was unaffected by Cmu infection. An upregulation of Ptgfr and a down-regulation of Ptegr4 mRNA expression was observed in the uterine horn following Cmu infection. These results indicate that Cmu infection alters contractility and prostaglandin signalling in the female reproductive tract but the effects are localised to specific regions.

Distribution and Regulation of ENaC Subunit and CFTR mRNA Expression in Murine Female Reproductive Tract

2002 ◽  
Vol 185 (2) ◽  
pp. 165-176 ◽  
Author(s):  
L.N. Chan ◽  
L.L. Tsang ◽  
D.K. Rowlands ◽  
L.G. Rochelle ◽  
R.C. Boucher ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Reproductive Tract ◽  
Female Reproductive Tract

scholarly journals Leukotrienes modulate secretion of progesterone and prostaglandins during the estrous cycle and early pregnancy in cattle: an in vivo study

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 767-776 ◽  
Author(s):  
Anna J Korzekwa ◽  
Mamadou M Bah ◽  
Andrzej Kurzynowski ◽  
Karolina Lukasik ◽  
Agnieszka Groblewska ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Estrous Cycle ◽  
Early Pregnancy ◽  
Luteal Phase ◽  
Reproductive Tract ◽  
Cell Function ◽  
Ovarian Cell

Recently, we showed that leukotrienes (LTs) regulate ovarian cell functionin vitro. The aim of this study was to examine the role of LTs in corpus luteum (CL) function during both the estrous cycle and early pregnancyin vivo. mRNA expression of LT receptors (BLTfor LTB4andCYSLTfor LTC4), and 5-lipoxygenase (5-LO) in CL tissue and their localization in the ovary were studied during the estrous cycle and early pregnancy. Moreover, concentrations of LTs (LTB4and C4) in the CL tissue and blood were measured.5-LOandBLTmRNA expression increased on days 16–18 of the cycle, whereasCYSLTmRNA expression increased on days 16–18 of the pregnancy. The level of LTB4was evaluated during pregnancy compared with the level of LTC4, which increased during CL regression. LT antagonists influenced the duration of the estrous cycle: the LTC4antagonist (azelastine) prolonged the luteal phase, whereas the LTB4antagonist (dapsone) caused earlier luteolysisin vivo. Dapsone decreased progesterone (P4) secretion and azelastine increased P4secretion during the estrous cycle. In summary, LT action in the bovine reproductive tract is dependent on LT type: LTB4is luteotropic during the estrous cycle and supports early pregnancy, whereas LTC4is luteolytic, regarded as undesirable in early pregnancy. LTs are produced/secreted in the CL tissue, influence prostaglandin function, and serve as important factors during the estrous cycle and early pregnancy in cattle.

scholarly journals New Insights into Development of Female Reproductive Tract—Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development

2021 ◽  
Vol 22 (3) ◽  
pp. 1211
Author(s):  
Ryuma Haraguchi ◽  
Gen Yamada ◽  
Aki Murashima ◽  
Daisuke Matsumaru ◽  
Riko Kitazawa ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Cell Tracking ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Mouse Uterus ◽  
Uterine Growth ◽  
Mullerian Ducts ◽  
Radial Axis ◽  
Hedgehog Signal

The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.

Soybean-Derived Phytoestrogens Regulate Prostaglandin Secretion in Endometrium During Cattle Estrous Cycle and Early Pregnancy

2005 ◽  
Vol 230 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Izabela Wolawek-Potocka ◽  
Mamadou M. Bah ◽  
Anna Korzekwa ◽  
Mariusz K. Piskula ◽  
Wieslaw Wiczkowski ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Early Pregnancy ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Reproductive Efficiency ◽  
Control Group ◽  
In Vivo Experiment ◽  
The Mean

Phytoestrogens acting as endocrine disruptors may induce various pathologies in the female reproductive tract. The purpose of this study was to determine whether phytoestrogens present in the soybean and/or their metabolites are detectable in the plasma of cows fed a diet rich in soy and whether these phytoestrogens influence reproductive efficiency and prostaglandin (PG) synthesis during the estrous cycle and early pregnancy in the bovine endometrium. In in vivo Experiment 1, we found significant levels of daidzein and genistein in the fodder and their metabolites (equol and p-ethyl-phenol) in bovine serum and urine. The mean number of artificial inseminations (Als) and pregnancy rates in two kinds of herds, control and experimental (cows fed with soybean 2.5 kg/day), were almost double in the soy-diet herd in comparison with the control animals. In in vivo Experiment 2, three out of five heifers fed soybean (2.5 kg/day) became pregnant whereas four out of five heifers in the control group became pregnant. The concentrations of a metabolite of PGF2α (PGFM) were significantly higher in the blood plasma of heifers fed a diet rich in soybean than those in the control heifers throughout the first 21 days after ovulation and AI. The higher levels of PGFM were positively correlated with equol and p-ethyl phenol concentrations in the blood. In in vitro experiments, the influence of isoflavones on PG secretion in different stages of the estrous cycle was studied. Although all phytoestrogens augmented the output of both PGs throughout the estrous cycle, equol and p-ethyl-phenol preferentially stimulated PGF2α output. The results obtained lead to the conclusion that soy-derived phytoestrogens and their metabolites disrupt reproductive efficiency and uterus function by modulating the ratio of PGF2α to PGE2, which leads to high, nonphysiological production of luteolytic PGF2α in cattle during the estrous cycle and early pregnancy.

scholarly journals Expression of IL-23 in Gilt Endometrium and Oviduct After Insemination With Seminal Plasma, Spermatozoa or Semen Extender

2020 ◽  
Author(s):  
Anna Svensson ◽  
Jatesada Jiwakanon ◽  
Caroline Fossum ◽  
Anne-Marie Dalin
Keyword(s):  
Inflammatory Response ◽  
Mrna Expression ◽  
Seminal Plasma ◽  
Reproductive Tract ◽  
Seminal Fluid ◽  
Female Reproductive Tract ◽  
Control Group ◽  
Treatment Groups ◽  
Semen Extender ◽  
Interleukin 23

Abstract Background: Signaling between seminal fluid and the female reproductive tract is required for a successful pregnancy to occur. Insemination with spermatozoa, seminal plasma and extender, is known to cause a rapid inflammatory response in the pig endometrium, which is characterized by an influx of neutrophils into the uterus. The temporary inflammatory response to semen involves induction of cytokines. In this study, potential functions for Interleukin-23 (IL-23) in the inflammatory response to different insemination treatments were examined by studying mRNA expression and immunostaining in samples of gilt oviduct (isthmus and infundibulum) and endometrium collected 35-40 h after insemination. Insemination was performed with either seminal plasma (SP, n = 4), spermatozoa in the extender Beltsville thawing solution (BTS) (SPZ, n = 4), or BTS alone (n = 4). In control gilts (n = 4) an insemination catheter was inserted without anything being inseminated. Any relation between expression of IL-23 and the presence of polymorphonuclear neutrophilic granulocytes (PMNs) in the endometrium was examined. Results: Results showed that IL-23 mRNA was expressed in the oviduct and in the endometrium. There was a significantly lower IL-23 mRNA expression in samples from gilts in the SPZ, SP and BTS treatment groups, compared with the controls. The control group also displayed significantly more neutrophils in samples collected 35-40 h after insemination compared with samples from the SP group. IL-23 immunolabelling was detected in a small number of separate cells as well as in the sub-epithelial connective tissue of the endometrium, the endosalpinx of the isthmus and infundibulum.Conclusions: All fluids used for insemination decreased the expression of IL-23 mRNA in the endometrium compared to catheter-insertion alone, indicating a possible role for IL-23 in the inflammatory response after insemination in gilts.

scholarly journals Expression Profile of VEGF and VEGFR2 in the Female Reproductive Tract at the Time of Placentation in a Porcine Model of Von Willebrand Disease Type 1

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3776-3776
Author(s):  
Mario von Depka ◽  
Mahnaz Ekhlasi-Hundrieser ◽  
Carsten Detering ◽  
Stefanie Lehner ◽  
Christiane Pfarrer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Pregnancy ◽  
Reproductive Tract ◽  
Porcine Model ◽  
Conflicts Of Interest ◽  
Von Willebrand Disease ◽  
Female Reproductive Tract ◽  
Von Willebrand

Abstract Objectives: Clinical studies showed that women affected by von Willebrand disease (VWD) trend towards higher rates of miscarriages, but the underlying pathomechanisms remain unclear. Several in vitro studies demonstrated an influence of von Willebrand factor (VWF) on angiogenesis, which seems to be partly mediated via VEGF. Since angiogenesis in the reproductive organs is essential to establish and maintain pregnancy, we aimed to investigate gene expression of VWF, VEGF, and its receptor VEGFR2 in non-pregnant and pregnant individuals, using a porcine model of VWD type 1. Methods: Tissue samples of uterus, oviduct and ovary were harvested from eight female pigs of which four were pregnant on day 30 (time of placentation) and four were non-pregnant and in estrus. Of each group, two were affected by VWD type 1 and two were wildtype (WT) individuals. The gene expression of VWF, VEGF, and VEGFR2 was measured by qRT-PCR and relatively quantified against the endothelial specific housekeeping genes PROCR and CD31 using the ΔΔCT method and calculating the respective x-fold changes. The gene expression differences were compared between both genotypes as well as between both reproductive states Mean differences were taken into account, if the divergences were consistent in both individuals of each group and not within the range of the group they were compared to. Results: Regarding the non-pregnant sows, VWF expression was lower in uterus and ovary of the VWD type 1 animals. This difference was not seen comparing the pregnant animals of each genotype, but the VWD type 1 animals showed higher VEGF expression in oviduct and higher VEGF and VEGFR2 expression in the ovary. The expression of VEGFR2 was reduced in the uterus. Comparing the non-pregnant with the pregnant animals within each genotype, the following results were found: the pregnant WT pigs showed increased expression of VEGFR2 in uterus and ovary, but decreased expression of VEGF in the uterus. For the pregnant VWD type 1 animals increased expression was found for VWF and VEGFR2 in the ovary, and decreased expression for VEGF in uterus and oviduct and VEGFR2 in the uterus. Discussion and Conclusion: Comparison of the different groups revealed differences of gene expression in the female reproductive tract during early pregnancy. The expectedly lower expression of VWF in the VWD type 1 animals was not found for the pregnant animals. Apparently, there is an increase of VWF levels during pregnancy as seen in women. While VEGFR2 expression in the uterus increases during placentation in the WT animals, it decreases in the VWD type 1 animals. This suggests altered regulation of early angiogenesis, which is essential during placentation. Expression of VEGF and VEGFR2 was increased in the ovaries of the VWD type 1 animals. This points to an enhanced involvement of this pathway during conversion of the ruptured follicles to sufficient corpora lutea graviditates, which may affect this process. Enhanced angiogenesis via the VEGF/VEGFR2-pathway due to lack of VWF was already shown in vitro. Our study shows that the expression of VEGF and VEGFR2 differs during early pregnancy in VWD type 1 compared to wildtype sows. Therefore, this pathway may influence angiogenesis in the reproductive tract. Disclosures No relevant conflicts of interest to declare.

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