Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids

Chakraborty, Indrani; Das, S K; Wang, Jinxi; Dey, S. K.

doi:10.1677/jme.0.0160107

Cited by 313 publications

(205 citation statements)

References 24 publications

(29 reference statements)

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“…In rats, the increase in EVP occurs late in the afternoon of day 5, whereas in hamsters and mice, it occurs in the afternoon and the evening of day 4 respectively. Previous studies in mice and hamsters have suggested a role of PTGS2, but not of PTGS1, in implantation (Chakraborty et al 1996, Lim et al 1999, Wang et al 2004, Pakrasi & Jain 2008 and also in decidualization and placentation in mice (Lim et al 1997, Wang et al 2007, Pakrasi & Jain 2008. The presence of Ptgs1 transcripts in the rat endometrium prior to implantation is in agreement with the hamster study ( Wang et al 2004), where it was detected as early as days 1 and 3, before the initiation of implantation occurs.…”

Section: Discussionsupporting

confidence: 82%

“…However, down-regulation of Ptgs1 mRNA at 4 h after the deciduogenic stimulus in the rat endometrium appears to be different from the results reported in mice. In mice, no changes in Ptgs1 transcripts were detected at any time after a deciduogenic stimulus (Lim et al 1997), and down-regulation of Ptgs1 transcripts was only detected in pregnant animals at the time of blastocyst attachment (Chakraborty et al 1996). At this time, our study is the only one available reporting the expression of PTGS1 protein, a better indication of function than transcript levels, during early stages of the initiation of decidualization.…”

Section: Discussionmentioning

confidence: 78%

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Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

Gillio-Meina¹,

Phang²,

Mather³

et al. 2009

Reproduction

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To determine if changes in endometrial expression of the enzymes and receptors involved in prostaglandin (PG) synthesis and action might provide insights into the PGs involved in the initiation of decidualization, ovariectomized steroid-treated rats at the equivalent of day 5 of pseudopregnancy were given a deciduogenic stimulus and killed at various times up to 32 h thereafter. The expression of PG-endoperoxide synthases (PTGS1 and PTGS2), microsomal PGE synthases (PTGES and PTGES2), cytosolic PGE synthase (PTGES3), prostacyclin synthase (PTGIS), prostacyclin receptor, peroxisome proliferator-activated receptor d (PPARD) and retinoid x receptor a (RXRA) in endometrium was assessed by semiquantitative RT-PCR, western blot analyses and immunohistochemistry. In addition, to determine which PG is involved in mediating decidualization, we compared the ability of PGE 2 , stable analogues of PGI 2 , L165041 (an agonist of PPARD), and docasahexanoic acid (an agonist of RXRA) to increase endometrial vascular permeability (EVP, an early event in decidualization), and decidualization when infused into the uterine horns of rats sensitized for the decidual cell reaction (DCR). EVP was assessed by uterine concentrations of Evans blue 10 h after initiation of infusions. DCR was assessed by the uterine mass 5 days after the initiation of the infusions. Because enzymes associated with the synthesis of PGE 2 , including PTGS2, are up-regulated in response to a deciduogenic stimulus and because PGE 2 was more effective than the PGI 2 analogues and PPARD and RXRA agonists in increasing EVP and inducing decidualization, we suggest that PGE 2 is most likely the PG involved in the initiation of decidualization in the rat.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 78%

Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

Gillio-Meina¹,

Phang²,

Mather³

et al. 2009

Reproduction

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“…Recent evidence demonstrates that PTGS2 expression during attachment reaction is critical to implantation (Chakraborty et al 1996). It is expressed in the uterus, blastocyst or both in a variety of species, and COX2 in turn up-regulates PG, primarily prostacyclin, that induces VEGF needed for vascular permeability and angiogenesis during implantation (Matsumoto et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Puerarin, a selective oestrogen receptor modulator, disrupts pregnancy in rats at pre-implantation stage

Saha¹,

Saraswat²,

Chakraborty³

et al. 2012

Reproduction

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The tubers of Pueraria tuberosa have folkloric repute as emmenagogue. The n-BuOH fraction of the ethanolic extract of tubers exhibits significant antifertility activity in laboratory animals. The present investigation explored the active principle(s) of the tuber extract with reference to contragestive effects in rats and probed the possible mechanism of action. Bioactivity-guided fractionation identified puerarin as the major constituent that exerted pregnancy-terminating effects. Oral administration of puerarin at R300 mg/kg per day for days (D) 1-2 post-coitus resulted in complete implantation failure. Serum oestradiol levels during D2-D5 and progesterone (P 4 ) level on D5 remained unaffected, but the endometrial expression of oestrogen receptor a (ERa) and ERb was adversely modulated that disrupted the implantation-specific characteristic endometrial oestrogenic milieu. The eventual consequence was loss of endometrial receptivity characterised by down-regulation of the uterine expression of P 4 receptor (PR) and attenuation of endometrial expression of leukaemia inhibitory factor, vascular endothelial growth factor and cyclo-oxygenase-2, the three important signalling molecules involved in the process of implantation. Light microscopic examination of the embryos demonstrated no untoward effect of puerarin on the development of embryos until D4, but D5 blastocysts underwent gross morphological distortion. The findings taken together are interpreted to suggest that puerarin adversely impacts the uterine expression of ER and PR that disrupts the implantation-conducive uterine milieu and prevents implantation. In conclusion, puerarin may be envisaged as a prospective molecule that merits further exploration for the development of non-steroidal post-coital contraceptive for women.

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“…PTGS2 is a rate-limiting enzyme involved in prostaglandin synthesis, is up-regulated in the LE adjacent to the blastocyst trophectoderm and then in decidualizing stromal cells, and is required for implantation and placentation in mice (52,53). Here, PTGS2 expression was induced in the LE adjacent to the blastocyst in adult FOXA2-deficient mice but not in the surrounding stroma, which was also observed in Lif-null and PUGKO Pgr Cre/+ Foxa2 f/f UGKO mice (11,26).…”

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

126

177

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Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.T he uterus is comprised of two tissue compartments, the endometrium and the myometrium. The endometrium contains three cell types, luminal epithelium (LE), glandular epithelium (GE), and stroma. In mice, the uterus becomes receptive to blastocyst implantation on gestational day (GD) 4 (with the observation of a postcoital vaginal plug designated GD 0.5); it is prereceptive on GD 1-3, and by the afternoon of GD 5 it becomes nonreceptive (refractory) (1-3). Dynamic changes in ovarian estrogen and progesterone production act via the uterus to regulate uterine receptivity, blastocyst implantation, and stromal cell decidualization necessary for the establishment of pregnancy (4-6). The implantation process, which is initiated by the attachment of the blastocyst trophectoderm to the receptive LE, occurs before or right after midnight in the evening of GD 4 and becomes more prominent by the morning of GD 5. By GD 6, the trophectoderm begins to contact directly stromal cells that then begin to differentiate into decidual cells, which are required for successful pregnancy because they regulate placental development and local maternal immune responses (7,8).The infertility observed in leukemia inhibitory factor (Lif)-null mice and uterine gland-knockout (UGKO) mice and sheep established ...

show abstract

Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids

Cited by 313 publications

References 24 publications

Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

Puerarin, a selective oestrogen receptor modulator, disrupts pregnancy in rats at pre-implantation stage

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

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