Nodal Promotes Functional Luteolysis via Down-Regulation of Progesterone and Prostaglandins E2 and Promotion of PGF2α Synthetic Pathways in Mare Corpus Luteum.
Abstract: In the present work, we investigated the role of Nodal, an embryonic morphogen from the TGFβ superfamily in corpus luteum (CL) secretory activity using cells isolated from equine CL as a model. Expression pattern of Nodal and its receptors activin receptor A type IIB (ACVR2B), activin receptor-like kinase (Alk)-7, and Alk4, as well as the Nodal physiological role, demonstrate the involvement of this pathway in functional luteolysis. Nodal and its receptors were immune localized in small and large luteal cells and endothelial cells, except ACVR2B, which was not detected in the endothelium. Nodal mRNA in situ hybridization confirmed its transcription in steroidogenic and endothelial cells. Expression analysis of the aforementioned factors evidenced that Nodal and Alk7 proteins peaked at the mid-CL (P < .01), the time of luteolysis initiation, whereas Alk4 and ACVR2B proteins increased from mid- to late CL (P < .05). The Nodal treatment of luteal cells decreased progesterone and prostaglandin (PG) E2 concentrations in culture media (P < .05) as well as mRNA and protein of secretory enzymes steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, cytosolic PGE2 synthase, and microsomal PGE2 synthase-1 (P < .05). Conversely, PGF2α secretion and gene expression of PG-endoperoxidase synthase 2 and PGF2α synthase were increased after Nodal treatment (P < .05). Mid-CL cells cultured with PGF2α had increased Nodal protein expression (P < .05) and phosphorylated mothers against decapentaplegic-3 phosphorylation (P < .05). Finally, the supportive interaction between Nodal and PGF2α on luteolysis was shown to its greatest extent because both factors together more significantly inhibited progesterone (P < .05) and promoted PGF2α (P < .05) synthesis than Nodal or PGF2α alone. Our results neatly pinpoint the sites of action of the Nodal signaling pathway toward functional luteolysis in the mare.
Publication Date: 2015-12-11 PubMed ID: 26653568DOI: 10.1210/en.2015-1362Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the role of a molecule called Nodal in the process of luteolysis in horses. That is, it explores how Nodal affects the breakdown of progesterone and the enhancement of a hormone called PGF2α, which impact the ovulation cycle in mares.
Background of the Study
- The study explores the role of a molecular pathway that involves Nodal in the process called luteolysis, which refers to the degradation of the corpus luteum—a temporary endocrine structure in female mammals.
- Nodal is known as an embryonic morphogen that belongs to the TGFβ superfamily, which plays key roles in embryogenesis and cellular differentiation.
- The researchers specifically wanted to understand how this pathway acts on the corpus luteum secretory activity using equine, or horse, cells as their test model.
Experiments and Findings
- The researchers found that Nodal and its receptor molecules were located in small and large luteal cells and certain endothelial cells—cells that line the inside of blood vessels.
- They noted that the concentrations of Nodal and one of its receptors, Alk7, were highest at the initiation of luteolysis, while other receptors increased later on in the process.
- When Nodal was applied to luteal cells, it decreased the concentrations of progesterone—a hormone important in pregnancy and menstruation—and prostaglandin E2, both crucial factors in the ovulation cycle.
- Conversely, the same treatment led to an increased secretion of another hormone called PGF2α, which usually rises during the menstruation phase when the body stops maintaining the environment for a fertilized egg.
- This occurred through a greater expression of certain genes that synthesize PGF2α.
- The researchers also found that the introduction of PGF2α induced the greater production of Nodal protein and other related molecules.
Conclusions
- The team concluded that Nodal significantly decreased the production of progesterone and increased the production of PGF2α more than either Nodal or PGF2α did alone.
- These findings highlight the specific mechanisms through which the Nodal signalling pathway contributes to functional luteolysis in horses—providing deep insights into ovulation and possibly pointing to new strategies to control animal fertility.
Cite This Article
APA
Galvão A, Skarzynski D, Ferreira-Dias G.
(2015).
Nodal Promotes Functional Luteolysis via Down-Regulation of Progesterone and Prostaglandins E2 and Promotion of PGF2α Synthetic Pathways in Mare Corpus Luteum.
Endocrinology, 157(2), 858-871.
https://doi.org/10.1210/en.2015-1362 Publication
Researcher Affiliations
- Institute of Animal Reproduction and Food Research (A.G., D.S.), Polish Academy of Sciences, 10-748 Olsztyn, Poland; Faculty of Veterinary Medicine (A.G., G.F.-D.), Centre for Interdisciplinary Research in Animal Health, University of Lisbon, 1300-477 Lisbon, Portugal.
- Institute of Animal Reproduction and Food Research (A.G., D.S.), Polish Academy of Sciences, 10-748 Olsztyn, Poland; Faculty of Veterinary Medicine (A.G., G.F.-D.), Centre for Interdisciplinary Research in Animal Health, University of Lisbon, 1300-477 Lisbon, Portugal.
- Institute of Animal Reproduction and Food Research (A.G., D.S.), Polish Academy of Sciences, 10-748 Olsztyn, Poland; Faculty of Veterinary Medicine (A.G., G.F.-D.), Centre for Interdisciplinary Research in Animal Health, University of Lisbon, 1300-477 Lisbon, Portugal.
MeSH Terms
- Activin Receptors, Type I / genetics
- Activin Receptors, Type I / metabolism
- Activin Receptors, Type II / genetics
- Activin Receptors, Type II / metabolism
- Animals
- Cholesterol Side-Chain Cleavage Enzyme / genetics
- Cholesterol Side-Chain Cleavage Enzyme / metabolism
- Corpus Luteum / metabolism
- Dinoprostone / biosynthesis
- Dinoprostone / metabolism
- Down-Regulation
- Female
- Gene Expression Regulation
- Horses
- Hydroxyprostaglandin Dehydrogenases / genetics
- Hydroxyprostaglandin Dehydrogenases / metabolism
- Intramolecular Oxidoreductases / genetics
- Intramolecular Oxidoreductases / metabolism
- Luteolysis / genetics
- Luteolysis / metabolism
- Nodal Protein / genetics
- Nodal Protein / metabolism
- Phosphoproteins / genetics
- Phosphoproteins / metabolism
- Progesterone / metabolism
- Prostaglandin-E Synthases
- RNA, Messenger / metabolism
Citations
This article has been cited 3 times.- Budik S, Walter I, Leitner MC, Ertl R, Aurich C. Expression of Enzymes Associated with Prostaglandin Synthesis in Equine Conceptuses.. Animals (Basel) 2021 Apr 20;11(4).
- Walewska E, Wołodko K, Skarzynski D, Ferreira-Dias G, Galvão A. The Interaction Between Nodal, Hypoxia-Inducible Factor 1 Alpha, and Thrombospondin 1 Promotes Luteolysis in Equine Corpus Luteum.. Front Endocrinol (Lausanne) 2019;10:667.
- Çilgin H. Can a cyclooxygenase inhibitor be an option for treatment of ovarian hyperstimulation syndrome?. Drug Des Devel Ther 2019;13:1099-1105.
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