Expression of Porcine Endometrial Prostaglandin Synthase During the Estrous Cycle and Early Pregnancy, and Following Endocrine Disruption of Pregnancy1

Ashworth, Morgan D.; Ross, Jason W.; Hu, Jianbo; White, Frankie J.; Stein, Daniel R.; DeSilva, Udaya; Johnson, Gregory A.; Spencer, Thomas E.; Geisert, Rodney D.

doi:10.1095/biolreprod.105.046557

Cited by 70 publications

(65 citation statements)

References 40 publications

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“…Moreover, PGE 2 can be converted into PGF 2a by PG 9-ketoreductase/carbonyl reductase (CBR1). It was demonstrated that highly inducible forms of PTGS and PGE synthase in the porcine endometrium are PTGS2 (also known as PGHS-2 or COX-2; Ashworth et al 2006) and microsomal PGE synthase-1 (mPGES-1), respectively (Waclawik et al 2006).…”

Section: Role Of Pgs During Pregnancy Establishmentmentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F 2a (PGF 2a ) and E 2 (PGE 2 ) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE 2 . Conceptus PGE 2 could be amplified by PGE 2 feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon g and interferon d, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

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Section: Role Of Pgs During Pregnancy Establishmentmentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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“…In addition, conceptus estrogens modulate uterine gene expression responsible for uterine remodeling for implantation and placentation from days 13 to 25 of gestation (25). The importance of estrogen is underscored by the fact that premature exposure of the pregnant uterus to estrogen on days 9 and 10 results in degeneration of all pig conceptuses by day 15 (26).…”

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confidence: 99%

Uterine MHC Class I Molecules and β2-Microglobulin Are Regulated by Progesterone and Conceptus Interferons during Pig Pregnancy

Joyce

Burghardt

et al. 2008

The Journal of Immunology

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MHC class I molecules and β2-microglobulin (β2m) are membrane glycoproteins that present peptide Ags to TCRs, and bind to inhibitory and activating receptors on NK cells and other leukocytes. They are involved in the discrimination of self from non-self. Modification of these molecules in the placenta benefits pregnancy, but little is known about their genes in the uterus. We examined the classical class I swine leukocyte Ags (SLA) genes SLA-1, SLA-2, and SLA-3, the nonclassical SLA-6, SLA-7, and SLA-8 genes, and the β2m gene in pig uterus during pregnancy. Uterine SLA and β2m increased in luminal epithelium between days 5 and 9, then decreased between days 15 and 20. By day 15 of pregnancy, SLA and β2m increased in stroma and remained detectable through day 40. To determine effects of estrogens, which are secreted by conceptuses to prevent corpus luteum regression, nonpregnant pigs were treated with estradiol benzoate, which did not affect the SLA or β2m genes. In contrast, progesterone, which is secreted by corpora lutea, increased SLA and β2m in luminal epithelium, whereas a progesterone receptor antagonist (ZK137,316) ablated this up-regulation. To determine effects of conceptus secretory proteins (CSP) containing IFN-δ and IFN-γ, nonpregnant pigs were implanted with mini-osmotic pumps that delivered CSP to uterine horns. CSP increased SLA and β2m in stroma. Cell-type specific regulation of SLA and β2m genes by progesterone and IFNs suggests that placental secretions control expression of immune regulatory molecules on uterine cells to provide an immunologically favorable environment for survival of the fetal-placental semiallograft.

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“…In gilts, developing conceptuses secrete estrogens to signal its presence in the uterus [34], and the profile of E2 secretion by developing embryos coincides with estrogen receptor expression in the endometrium [32]. Changes occurred in the endometrium as a result of conceptus estrogen secretion include increased PGHS-2 expression [20,21] and PGE2 secretion [35]. The existence of the Hoxa10 / Pghs2 / PGE2 axis has previously been shown in uterine tissues of mice.…”

Section: Steroids Modulate Hoxa10 Expression In the Pigmentioning

confidence: 92%

“…The rate-limiting enzyme in PG production is prostaglandin H synthase (PGHS; also known as cyclooxygenase), which catalyzes the conversion of arachidonic acid to PGH2 [19], the common substrate for various PGs. Expression of PGHS-2 in the endometria of cyclic and early pregnant gilts has previously been demonstrated [20,21]. Interestingly, Hoxa10 null mice lack Pghs2 expression in stromal cells of the endometrium.…”

mentioning

confidence: 89%

Effect of Steroids on HOXA10 mRNA and Protein Expression and Prostaglandin Production in the Porcine Endometrium

Blitek

Kiewisz

Wacławik

et al. 2010

Journal of Reproduction and Development

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Abstract. The homeobox A (HOXA) family of genes is responsible for segmental development of the female reproductive tract during embryogenesis. However, HOXA10 has been shown to be essential not only for uterus development, but also for implantation. Persistent expression and steroid-dependent regulation of this gene has been demonstrated in adult human, primate, murine and canine uteri. Moreover, HOXA10-dependent expression of prostaglandin H synthase-2 (PGHS-2), a key enzyme in prostaglandin production, has been previously detected. The role of the HOXA10 gene in the porcine uterus is not well established. Therefore, the present studies were undertaken to 1) examine the effect of E2 and P4 on HOXA10 mRNA and protein content in the endometrium collected on day 9 of the estrous cycle and 2) determine the PGHS-2 protein expression and PGE2 and PGF2α secretion from endometrial tissue in response to steroid treatment. Endometrial explants collected from mature gilts on day 9 of the estrous cycle were incubated with E2 (1-100 nM), P4 (10-1000 nM) or E2 (10 nM) and P4 (100 nM) for 24 h. E2 alone or E2 in the presence of P4 increased HOXA10 mRNA expression in the endometrium (P<0.05). The HOXA10 protein level was upregulated in response to E2, P4 and both steroids administered simultaneously (P<0.05). Moreover, E2 and P4 stimulated PGHS-2 protein expression in cultured endometrial explants. PGE2, but not PGF2α, secretion increased in the presence of E2 (P<0.05). However, the release of both prostaglandins was decreased after treatment of endometrial explants with the highest dose of P4 (P<0.01). These results demonstrate that E2 and P4 are important regulators of HOXA10 gene expression in the adult porcine endometrium during the mid-luteal phase of the estrous cycle. Additionally, the similar profiles of endometrial HOXA10 and PGHS-2 expression in the presence of E2 and P4 indicate that both genes are simultaneously regulated by steroids in the porcine uterus. Key words: Endometrium, Estradiol, HOXA10, PGHS-2, Pig, Progesterone, Prostaglandins (J. Reprod. Dev. 56: [643][644][645][646][647][648] 2010) he uterine endometrium is one of the most dynamic tissues in the organism, undergoing morphological and physiological changes during each estrous cycle. Disorders in endometrial development may lead to lack of or improper implantation, pregnancy failure or infertility. Among the different hormones, estradiol (E2) and progesterone (P4) of ovarian origin are crucial regulators of endometrial receptivity and embryo-maternal cross-talk in many species [1][2][3][4]. It is obvious that the action of P4 in priming the uterus is absolutely essential to attain uterine receptivity for implantation, but the requirement of E2 of ovarian origin is speciesspecific [1]. However, the molecular mechanisms that direct the ordered proliferation, differentiation and cell death associated with the normal menstrual or estrous cycles are still not well characterized. Good candidates for regulation of gene expression in the endometrium are ho...

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Expression of Porcine Endometrial Prostaglandin Synthase During the Estrous Cycle and Early Pregnancy, and Following Endocrine Disruption of Pregnancy1

Cited by 70 publications

References 40 publications

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Uterine MHC Class I Molecules and β2-Microglobulin Are Regulated by Progesterone and Conceptus Interferons during Pig Pregnancy

Effect of Steroids on HOXA10 mRNA and Protein Expression and Prostaglandin Production in the Porcine Endometrium

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