Abstract: Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin Fα, E and I synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Control mares (n = 5; C group) received 6 mL of saline im, whereas OXT (60 units/mare) was administered im (n = 6; OXT group), every 12 hours, on days 7 to 14 postovulation. After endometrial biopsy in groups C (Day 10) and OXT (Day 24), luteolysis occurred within 3 or 6 days, respectively. Luteal maintenance took place in 4 of 6 (67%) of OXT-treated mares. Progesterone in C group was the highest on biopsy day (P < 0.05). In OXT mares, PTGS2, ESR1 (P < 0.05), PTGES, PTGIS, PGR, and ESR2 (P < 0.01) gene transcription decreased, whereas OXTR increased (P < 0.05) in comparison with the C group. In OXT-treated mares, endometrial ESR2 protein expression decreased (P < 0.05), but OXTR increased (P < 0.05) compared with control animals. In both experimental groups, PTGS2 was mainly immunolocalized in surface epithelium, whereas AKR1C3, PTGES, PTGIS, and PGR were in surface and glandular epithelia. ESR1 and ESR2 were found in glandular epithelium and OXTR in stromal cells. High immunolabeling for PTGES, PTGIS, PGR, and OXTR and low for ESR2 was detected in endometrium of OXT-group mares with extended diestrus. Prolonged luteal function associated with chronic OXT treatment may be related to different spatial expression of OXTR and PGR in the endometrium. The observed reduction of endometrial ESR2 may be responsible for the maintenance of PGR in luminal and glandular epithelium. Also, ESR2 may attenuate the transcriptional activity of ESR1 in mare endometrium. This study offers new knowledge on the endometrial expression of ovarian steroids and OXT receptors in OXT pharmacologically induced luteal maintenance in the mare.
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The research article investigates the effects of continuous administration of oxytocin on the luteal phase in mare reproduction. The study focuses specifically on the impact of oxytocin on the maintenance of the luteal phase and the expression of important proteins involved in hormone regulation, contributing new insights into ovarian hormone and oxytocin receptor behavior in the process.
Objective of the Study
The main aim of the study was to understand how sustained oxytocin administration impacts the maintenance of the luteal phase in mares – a biological stage crucial to pregnancy.
Additionally, the researchers analyzed the endometrial expression of several proteins involved in hormone production and regulation (PTGS2, AKR1C3, PTGES, PTGIS, OXTR, PGR, ESR1, ESR2) in mares with luteal maintenance after chronic oxytocin administration.
Methodology
The study was performed with two groups of mares. The control group (C group) received 6mL of saline, whereas the test group (OXT group) received 60 units of oxytocin every 12 hours, from days 7 to 14 post ovulation.
Endometrial biopsies were conducted on the C group on day 10 and on the OXT group on day 24. The researchers monitored the time it took for luteolysis (the degradation of the corpus luteum) to occur in each group.
Findings
Among the mares in the OXT group, 67% experienced luteal maintenance. The researchers identified changes in the transcription (a key process in gene expression) of several genes in these mares, compared to the control group. In terms of protein expression, the study detected an increase in oxytocin receptors (OXTRs) and a decrease in estrogen receptors (ESR2).
A higher concentration of progesterone was found in the control group on biopsy day.
The study also found a differential spatial location of OXTRs and progesterone receptors (PGRs), localized in diverse endometrium layers.
Implications
The article suggests that extended luteal function, seen in mares treated with oxytocin, might be connected to the different expression patterns of OXTR and PGR in the endometrium.
The observed decrease in ESR2 likely contributes to the maintenance of PGR in luminal and glandular epithelium. Furthermore, it may attenuate the transcriptional activity of ESR1 in the mare endometrium.
The discovery adds to the body of knowledge related to the endometrial expression of ovarian steroids and oxytocin receptors, particularly regarding pharmacologically induced luteal maintenance in mares.
Cite This Article
APA
Rebordão MR, Galvão A, Pinto-Bravo P, Pinheiro J, Gamboa S, Silva E, Mateus L, Ferreira-Dias G.
(2016).
Endometrial prostaglandin synthases, ovarian steroids, and oxytocin receptors in mares with oxytocin-induced luteal maintenance.
Theriogenology, 87, 193-204.
https://doi.org/10.1016/j.theriogenology.2016.08.028
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Animal Science, Coimbra College of Agriculture, Coimbra, Portugal.
Galvão, António
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland.
Pinto-Bravo, Pedro
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Animal Science, Coimbra College of Agriculture, Coimbra, Portugal.
Pinheiro, Joana
Department of Animal Science, Coimbra College of Agriculture, Coimbra, Portugal.
Gamboa, Sandra
Department of Animal Science, Coimbra College of Agriculture, Coimbra, Portugal.
Silva, Elisabete
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
Mateus, Luísa
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
Ferreira-Dias, Graça
CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal. Electronic address: gmlfdias@fmv.ulisboa.pt.
MeSH Terms
Animals
Corpus Luteum / drug effects
Corpus Luteum / physiology
Estrogens / genetics
Estrogens / metabolism
Female
Horses / physiology
Ovary / physiology
Oxytocics / pharmacology
Oxytocin / pharmacology
Progestins / genetics
Progestins / metabolism
Prostaglandin-Endoperoxide Synthases / genetics
Prostaglandin-Endoperoxide Synthases / metabolism
Receptors, Estrogen / genetics
Receptors, Estrogen / metabolism
Receptors, Oxytocin / genetics
Receptors, Oxytocin / metabolism
Receptors, Progesterone / genetics
Receptors, Progesterone / metabolism
Citations
This article has been cited 3 times.
Bae SJ, Jo Y, Cho MK, Jin JS, Kim JY, Shim J, Kim YH, Park JK, Ryu D, Lee HJ, Joo J, Ha KT. Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics. Front Endocrinol (Lausanne) 2022;13:942368.
Rebordão MR, Amaral A, Fernandes C, Silva E, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF(2α) Pathway in the Mare Endometrium. Animals (Basel) 2021 Sep 6;11(9).
Lyu LK, Li JS, Wang XJ, Yao YJ, Li JF, Li Y, Wen HS, Qi X. Arg-Vasotocin Directly Activates Isotocin Receptors and Induces COX2 Expression in Ovoviviparous Guppies. Front Endocrinol (Lausanne) 2021;12:617580.