Comprehensive expression analysis of prostanoid enzymes and receptors in the human endometrium across the menstrual cycle

Catalano, Rob D.; Wilson, Martin; Boddy, Sheila C.; Jabbour, Henry N.

doi:10.1093/molehr/gaq094

Cited by 58 publications

(51 citation statements)

References 60 publications

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“…PGs are catabolized mainly by hydroxyprostaglandin dehydrogenase (HPGD) to terminate their action [17]. Expression of HPGD in the uterine endometrium has been reported for humans [18], mice [19], and cows [20] but not pigs. Expression of PTGS1, PTGS2, PTGES, and CBR1 has been reported in the uterine endometrium during early pregnancy in pigs [9,[21][22][23], but expression of these during the later stage of pregnancy and other enzymes involved in PGE 2 and PGF 2a synthesis and metabolism during pregnancy has not been completely studied in pigs.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Prostaglandin Metabolic Enzyme Expression During Pregnancy and the Characterization of AKR1B1 as a Prostaglandin F Synthase at the Maternal-Conceptus Interface in Pigs1

Seo

Choi

Shim

et al. 2014

Biology of Reproduction

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Prostaglandins (PGs) are important lipid mediators regulating various reproductive processes in many species. In pigs, the expression pattern of PGE2 and PGF2α metabolic enzymes and the regulatory mechanism controlling PGE2 and PGF2α levels in the uterus during pregnancy are not completely understood. This study determined endometrial expression of the genes (PLA2G4A, PTGS1, PTGS2, PTGES, PTGES2, PTGES3, AKR1B1, CBR1, and HPGD) involved in PGE2 and PGF2α metabolism during the estrous cycle and pregnancy and measured levels of PGE2 and PGF2α in uterine endometrial tissues and uterine flushings at the time of conceptus implantation in pigs. Except PTGES3, expression of the genes studied changed in a pregnancy-stage-specific manner, and localization of PTGES, AKR1B1, CBR1, and HPGD mRNAs were cell-type specific in the uterine endometrium. Levels of both PGE2 and PGF2α in uterine endometrial tissues and uterine lumen were higher on Day 12 of pregnancy than those of the estrous cycle and affected by different morphology of spherical and filamentous conceptuses. Furthermore, we determined that endometrial expression of AKR1B1, known to encode a PGF2α synthase in other species, was increased by estrogen and interleukin-1beta and that AKR1B1 exhibited PGF2α synthase activity in the porcine uterine endometrium. These results in pigs indicate that the PGE2 and PGF2α metabolic enzymes are expressed stage specifically in the endometrium during pregnancy and regulate the abundance of PGE2 and PGF2α in the uterus at the time of implantation and that AKR1B1 may act as a major PGF synthase in the endometrium during early pregnancy.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Prostaglandin Metabolic Enzyme Expression During Pregnancy and the Characterization of AKR1B1 as a Prostaglandin F Synthase at the Maternal-Conceptus Interface in Pigs1

Seo

Choi

Shim

et al. 2014

Biology of Reproduction

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“…Expression of AKR1C3 in the endometrium was described by Catalano and coworkers who reported peak mRNA expression in endometrial tissue homogenates from the early-secretory phase at a time when early stages of post-ovulatory remodelling and initiation of decidualisation are occurring in the endometrium (Catalano et al 2011). The same study reported that AKR1C3 was immunolocalised to glandular and luminal epithelial cells throughout the menstrual cycle (Catalano et al 2011).…”

Section: Androgen Biosynthesis and Expression Of Steroidmetabolising mentioning

confidence: 74%

“…Weak in the proliferative phase and moderate in the secretory phase protein expression in the endometrial stroma have been contradictory, with expression limited to glandular and luminal epithelium as reported by Catalano and coworkers (Catalano et al 2011); however, Hevir and coworkers demonstrated immunopositive staining in both stromal and epithelial cells (Hevir et al 2011). Our own studies showed conclusively that AKR1C3 mRNA and protein are both detectable in isolated human ESCs, and decidualisation results in a marked increase in AKR1C3 expression consistent with peak expression reported in the early-secretory-phase endometrial tissue homogenates (Gibson et al 2016).…”

Section: Protein Detected In Isolated Escsmentioning

confidence: 94%

Regulation of androgen action during establishment of pregnancy

Gibson¹,

Simitsidellis²,

Saunders³

2016

Journal of Molecular Endocrinology

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During the establishment of pregnancy, the ovarian-derived hormones progesterone and oestradiol regulate remodelling of the endometrium to promote an environment that is able to support and maintain a successful pregnancy. Decidualisation is characterised by differentiation of endometrial stromal cells that secrete growth factors and cytokines that regulate vascular remodelling and immune cell influx. This differentiation process is critical for reproduction, and inadequate decidualisation is implicated in the aetiology of pregnancy disorders such as foetal growth restriction and preeclampsia. In contrast to progesterone and oestradiol, the role of androgens in regulating endometrial function is poorly understood. Androgen receptors are expressed in the endometrium, and androgens are reported to regulate both the transcriptome and the secretome of endometrial stromal cells. In androgen-target tissues, circulating precursors are activated to mediate local effects, and recent studies report that steroid concentrations detected in endometrial tissue are distinct to those detected in the peripheral circulation. New evidence suggests that decidualisation results in dynamic changes in the expression of androgen biosynthetic enzymes, highlighting a role for pre-receptor regulation of androgen action during the establishment of pregnancy. These results suggest that such enzymes could be future therapeutic targets for the treatment of infertility associated with endometrial dysfunction. In conclusion, these data support the hypothesis that androgens play a beneficial role in regulating the establishment and maintenance of pregnancy. Future studies should be focussed on investigating the safety and efficacy of androgen supplementation with the potential for utilisation of novel therapeutics, such as selective androgen receptor modulators, to improve reproductive outcomes in women.

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“…Also, in female reproduction, PGD 2 is secreted from endometrium and myometrium in greater amounts [21]. Prostaglandin endoperoxidase synthase 1 or 2 (PTGS1 and PTGS2) converts arachidonic acid to PGH 2 which is converted by prostaglandin D synthases HPGDS and PTGDS to PGD 2 [22]. As a cytosolic enzyme, HPGDS is involved in immune response as it is expressed by inflammatory cells including mast cells, antigen-presenting cells, and Th2 cells in mammals.…”

Section: Discussionmentioning

confidence: 99%