Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2α by the uterine endometrium

Establishment of pregnancy in domestic ruminants includes pregnancy recognition signalling by the conceptus, implantation and placentation. Despite the high fertilisation success rate in ruminants, a significant amount of embryo loss occurs, primarily during early gestation. Interferon-tau (IFNT), a type I interferon that is exclusively secreted by the cells of the trophectoderm of the ruminant conceptus, has been recognised as the primary agent for maternal recognition of pregnancy in ruminants. It produces its antiluteolytic effect on the corpus luteum by inhibiting the expression of oxytocin receptors in the uterine epithelial cells, which prevents pulsatile, luteolytic secretion of prostaglandin F2α by the uterine endometrium. While the importance of IFNT in maternal recognition of pregnancy and prevention of luteolysis in ruminants is unequivocal, important questions, for example, relating to the threshold level of IFNT required for pregnancy maintenance, remain unanswered. This paper reviews data linking IFNT with measures of fertility in ruminants.

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Coding RNA Sequencing of Equine Endometrium during Maternal Recognition of Pregnancy

Genes ◽

10.3390/genes10100749 ◽

2019 ◽

Vol 10 (10) ◽

pp. 749 ◽

Cited By ~ 3

Author(s):

Kristin M. Klohonatz ◽

Stephen J. Coleman ◽

Alma D. Islas-Trejo ◽

Juan F. Medrano ◽

Ann M. Hess ◽

...

Keyword(s):

Gene Expression ◽

Sample Preparation ◽

Rna Sequencing ◽

Splice Variants ◽

Expression Patterns ◽

Prostaglandin F2α ◽

Endometrial Biopsy ◽

Pregnancy Status ◽

Maternal Recognition Of Pregnancy ◽

Uterine Lavage

Equine maternal recognition of pregnancy (MRP) is a process whose signal remains unknown. During MRP the conceptus and endometrium communicate to attenuate prostaglandin F2α (PGF) secretion, sparing the corpus luteum and maintaining progesterone production. Recognition of a mobile conceptus by the endometrium is critical by days 14–16 post-ovulation (PO), when endometrium produces PGF, initiating luteolysis. The objective of this study was to evaluate endometrial gene expression changes based upon pregnancy status via RNA sequencing. This experiment utilized a cross-over design with each mare serving as both a pregnant and non-mated control on days nine, 11, and 13 PO (n = 3/status/day). Mares were randomly assigned to collection day and pregnancy confirmed by terminal uterine lavage at the time of endometrial biopsy. Total RNA was isolated and libraries prepared using Illumina TruSeq RNA sample preparation kit. Reads were mapped and annotated using HISAT2 and Stringtie. Expression values were evaluated with DESEQ2 (P ≤ 0.05 indicated significance). On day nine, 11, and 13 there were 1435, 1435 and 916 significant transcripts, respectively. Multiple genes with splice variants had different expression patterns within the same day. These are the first data to evaluate the endometrial transcriptome during MRP on days nine, 11, and 13.

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Non-Coding RNA Sequencing of Equine Endometrium During Maternal Recognition of Pregnancy

Genes ◽

10.3390/genes10100821 ◽

2019 ◽

Vol 10 (10) ◽

pp. 821

Author(s):

Kristin M. Klohonatz ◽

Stephen J. Coleman ◽

Ashley D. Cameron ◽

Ann M. Hess ◽

Kailee J. Reed ◽

...

Keyword(s):

Small Rna ◽

Prostaglandin F2α ◽

Luteal Regression ◽

Production Studies ◽

Non Coding Rna ◽

Unknown Structure ◽

Non Coding Rnas ◽

Maternal Recognition Of Pregnancy ◽

And Function ◽

Small Rna Library

Maternal recognition of pregnancy (MRP) in the mare is not well defined. In a non-pregnant mare, prostaglandin F2α (PGF) is released on day 14 post-ovulation (PO) to cause luteal regression, resulting in loss of progesterone production. Equine MRP occurs prior to day 14 to halt PGF production. Studies have failed to identify a gene candidate for MRP, so attention has turned to small, non-coding RNAs. The objective of this study was to evaluate small RNA (<200 nucleotides) content in endometrium during MRP. Mares were used in a cross-over design with each having a pregnant and non-mated cycle. Each mare was randomly assigned to collection day 11 or 13 PO (n = 3/day) and endometrial biopsies were obtained. Total RNA was isolated and sequencing libraries were prepared using a small RNA library preparation kit and sequenced on a HiSeq 2000. EquCab3 was used as the reference genome and DESeq2 was used for statistical analysis. On day 11, 419 ncRNAs, representing miRNA, snRNA, snoRNA, scaRNA, and vaultRNA, were different between pregnancy statuses, but none on day 13. Equine endometrial ncRNAs with unknown structure and function were also identified. This study is the first to describe ncRNA transcriptome in equine endometrium. Identifying targets of these ncRNAs could lead to determining MRP.

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Effect of ovarian steroids on basal and oxytocin-induced prostaglandin F2α secretion from pig endometrial cells

Reproduction Fertility and Development ◽

10.1071/rd03024 ◽

2003 ◽

Vol 15 (4) ◽

pp. 197 ◽

Cited By ~ 9

Author(s):

Jianbo Hu ◽

Gheorghe T. Braileanu ◽

Mark A. Mirando

Keyword(s):

Epithelial Cells ◽

Stromal Cells ◽

Chronic Treatment ◽

Prostaglandin F2α ◽

Exocrine Secretion ◽

Apical Surface ◽

Stimulatory Action ◽

Endometrial Cells ◽

Oestradiol Treatment ◽

Luminal Epithelial Cells

These studies were undertaken to determine how treatment with 100 nM progesterone and/or 10 nM oestradiol-17β acutely (3 h; Experiment 1) or chronically (72 h; Experiments 2–4) influenced basal and oxytocin (OT)-stimulated prostaglandin (PG) F2α secretion, in enriched cultures of pig endometrial luminal epithelial, glandular epithelial and stromal cells obtained on Day 16 (Experiments 1, 2 and 4) or Day 12 (Experiment 3) after oestrus. In Experiment 1, acute treatment with progesterone stimulated PGF2α secretion from each cell type on Day 16, whereas acute oestradiol treatment inhibited the stimulatory action of progesterone on PGF2α secretion only in glandular epithelial cells. In Experiment 2, OT stimulated phospholipase (PL) C activity in luminal epithelial cells on Day 16 only in the presence of chronic oestradiol treatment. For glandular epithelial cells on Day 16, OT stimulated PLC activity only in the presence of chronic treatment with steroid. In stromal cells on Day 16, OT stimulated PLC activity in the absence of steroids and the response to OT was further enhanced by oestradiol. In the absence of chronic treatment with steroid, OT did not stimulate PGF2α secretion from luminal epithelial cells, but oestradiol induced a response to OT. For glandular epithelial cells, OT-induced PGF2α secretion was not altered by steroids, whereas the stimulatory response to OT was inhibited by oestradiol or progesterone in stromal cells. For endometrial cells obtained on Day 12 after oestrus in Experiment 3, OT only stimulated PGF2α release from glandular epithelial and stromal cells. For luminal epithelial cells obtained on Day 16 after oestrus and cultured under polarizing conditions in Experiment 4, secretion of PGF2α occurred preferentially from the basolateral surface and was stimulated by OT more from the basolateral surface than from the apical surface. Oxytocin-induced PGF2α secretion from the apical surface was enhanced by chronic treatment with oestradiol, whereas that from the basolateral surface was enhanced by chronic treatment with progesterone. In summary, oestradiol enhanced OT-induced PGF2α secretion from the apical surface of luminal epithelial cells and reduced the response of stromal cells to OT, actions that may contribute to the reorientation of PGF2α from endocrine secretion (i.e. towards the uterine vasculature) to exocrine secretion (i.e. towards the uterine lumen) during pregnancy recognition in pigs.

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Maternal Recognition of Pregnancy in Swine. II. Plasma Concentrations of Progesterone and 13,14-Dihydro-15-Keto-Prostaglandin F2α, during the Estrous Cycle and during Short and Long Pseudopregnancy in Gilts1

Biology of Reproduction ◽

10.1095/biolreprod55.3.590 ◽

1996 ◽

Vol 55 (3) ◽

pp. 590-597 ◽

Cited By ~ 8

Author(s):

Anthony E. Pusateri ◽

Matthew E. Wilson ◽

Mark A. Diekman

Keyword(s):

Estrous Cycle ◽

Plasma Concentrations ◽

Prostaglandin F2α ◽

Maternal Recognition Of Pregnancy

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Effect of Interferon-τ on Prostaglandin Biosynthesis, Transport, and Signaling at the Time of Maternal Recognition of Pregnancy in Cattle: Evidence of Polycrine Actions of Prostaglandin E2

Endocrinology ◽

10.1210/en.2004-0587 ◽

2004 ◽

Vol 145 (11) ◽

pp. 5280-5293 ◽

Cited By ~ 104

Author(s):

J. A. Arosh ◽

S. K. Banu ◽

S. Kimmins ◽

P. Chapdelaine ◽

L. A. MacLaren ◽

...

Keyword(s):

Prostaglandin F2α ◽

Receptor Expression ◽

Cellular Interactions ◽

Specific Expression ◽

Cyclooxygenase 1 ◽

Embryonic Origin ◽

Cox 2 ◽

Maternal Recognition Of Pregnancy ◽

Spatio Temporal ◽

Cox 1

Abstract Recognition and establishment of pregnancy involve several molecular and cellular interactions among the conceptus, uterus, and corpus luteum (CL). In ruminants, interferon-τ (IFNτ) of embryonic origin is recognized as the pregnancy recognition signal. Endometrial prostaglandin F2α (PGF2α) is the luteolysin, whereas PGE2 is considered a luteoprotective or luteotrophic mediator at the time of establishment of pregnancy. The interplay between IFNτ and endometrial PGs production, transport, and signaling at the time of maternal recognition of pregnancy (MRP) is not well understood. We have studied the expression of enzymes involved in metabolism of PGE2 and PGF2α, cyclooxygenase-1 (COX-1) and COX-2, PG synthases (PGES and PGFS), PG 15-dehydrogenase, and PG transporter as well as PGE2 (EP2 and EP3) and PGF2α receptors. IFNτ influences cell-specific expression of COX-2, PGFS, EP2, and EP3 in endometrium, myometrium, and CL in a spatio-temporal and tissue-specific manner, whereas it does not alter COX-1, PGES, PG 15-dehydrogenase, PG transporter, or PGF2α receptor expression in any of these tissues. In endometrium, IFNτ decreases PGFS in epithelial cells and increases EP2 in stroma. In myometrium, IFNτ decreases PGFS and increases EP2 in smooth muscle cells. In CL, IFNτ increases PGES and decreases EP3. Together, our results show that IFNτ directly or indirectly increases PGE2 biosynthesis and EP2-associated signaling in endometrium, myometrium, and CL during MRP. Thus, PGE2 may play pivotal roles in endometrial receptivity, myometrial quiescence, and luteal maintenance, indicating polycrine (endocrine, exocrine, paracrine, and autocrine) actions of PGE2 at the time of MRP. Therefore, the establishment of pregnancy may depend not only on inhibition of endometrial PGF2α, but also on increased PGE2 production in cattle.

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Maternal recognition of pregnancy in the horse: a mystery still to be solved

Reproduction Fertility and Development ◽

10.1071/rd10294 ◽

2011 ◽

Vol 23 (8) ◽

pp. 952 ◽

Cited By ~ 24

Author(s):

C. Klein ◽

M. H. T. Troedsson

Keyword(s):

Prostaglandin F2α ◽

Cyclooxygenase 2 ◽

Microarray Experiments ◽

Luteal Function ◽

Domestic Species ◽

Prostaglandin Release ◽

Conceptus Development ◽

Immunological Rejection ◽

Pregnancy Recognition ◽

Maternal Recognition Of Pregnancy

Maternal recognition of pregnancy in the horse is the sum of events leading to maintenance of pregnancy; in a narrow sense, maternal recognition of pregnancy refers to the physiological process by which the lifespan of the corpus luteum is prolonged. The horse is one of the few domestic species in which the conceptus-derived pregnancy recognition signal has not been identified. The presence of the conceptus reduces pulsatile prostaglandin F2α secretion by the endometrium during early gestation in the mare, partly attributed to the reduced expression of cyclooxygenase-2. Cyclooxygenase-2 has therefore been suggested as one of the regulators of endometrial prostaglandin F2α release modified by the antiluteolytic factor secreted by the conceptus. In addition, altered oxytocin responsiveness has been implicated in the adjustment of prostaglandin release in pregnant mares. While conceptus mobility has proven to be essential for establishment of pregnancy, conceptus-derived oestrogens and prostaglandins, principally prostaglandin E2, have not been confirmed as the critical antiluteolytic factor. Various ways to induce prolonged luteal function in the non-pregnant mare will be highlighted in the current review, specifically, how they may pertain to the process of maternal recognition of pregnancy. Furthermore, recently published microarray experiments comparing the transcriptome of pregnant and non-pregnant endometria and different stages of conceptus development will be reviewed. Findings include the prevention of conceptus adhesion, the provision of nutrients to the conceptus and the avoidance of immunological rejection, among others.

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