Early Maturation of Corpus Luteum in Rabbits - Effect of Sildenafil Citrate on Luteolytic Capacity in the Early Luteal Period

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dc.contributor.authorUcar, Eyyup Hakan
dc.contributor.authorPeker, Cevdet
dc.contributor.authorErdogan, Gunes
dc.contributor.authorKose, Mehmet
dc.contributor.authorAtli, Mehmet Osman
dc.date.accessioned2024-04-24T17:18:41Z
dc.date.available2024-04-24T17:18:41Z
dc.date.issued2023
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground: Prostaglandin F-2 alpha (PGF(2)alpha) binds to the specific receptor (PTGFR) on the corpus luteum (CL) in mammals, inducing regression of the CL structure (luteolysis) and initiating a new cycle. While PGF(2)alpha is effective only on mature CL, the immature CL structure (early luteal phase) resists PGF(2)alpha. In this study, sildenafil citrate, which is used to increase blood flow in the genital organs for treating specific pregnancy issues in women, was administered during the early luteal phase in a rabbit model to test the hypothesis of enhancing blood flow to the CL, thereby promoting earlier maturation and enabling a response to PGF(2)alpha. Materials, Methods & Results: The study was conducted in 2 sub-studies: clinical and molecular. A large number of rabbits were initially included in the sub-studies to ensure a sufficient number of pseudo-pregnant rabbits. Ovulation in rabbits was induced with buserelin acetate and was considered as day 0 of the study. The sub-studies were continued with rabbits whose pseudo-pregnancies were confirmed according to progesterone (P-4) results. As a result, the studies were continued with a total of 41 pseudo-pregnant New Zealand female rabbits, 21 of which were included in the clinical sub-study and 20 in the molecular sub-study. In both sub-studies, on day 3 of the luteal period, rabbits in the treatment group received 5 mg/kg sildenafil citrate and all rabbits received a single dose of exogenous PGF(2)alpha on day 4 to induce luteolysis. In the clinical sub-study, echotexture and intraovarian blood flow changes in the ovaries were determined by ultrasonography (USG) examination. In the molecular sub-study, the expression changes of Hypoxia Inducible Factor 1 Alpha (HIF1A) and Vascular Endothelial Growth Factor (VEGF) related to angiogenesis, Steroidogenic Acute Regulatory Protein (StAR) related to P-4 metabolism, Prostaglandin-Endoperoxide Synthase 2 (PTGS2) related to prostaglandin (PG) mechanism and 15-Hydroxyprostaglandin Dehydrogenase (HPGD) genes at mRNA level were determined using Real Time Polymerase Chain Reaction (RT-PCR) in CL tissues obtained with ovariohysterectomy (OVH) at 1 and 12 h after PGF(2)alpha injection. In addition, blood samples were collected for determine P-4 levels from all rabbits. In the clinical sub-study; there was no difference between the groups in mean gray values (MGV), whereas there was a significant decrease in both pulsatile index (PI) and resistance index (RI) values at 40 min after PGF(2)alpha injection (P < 0.05). In the molecular sub-study, it was determined that sildenafil citrate had no significant effect (P > 0.05) on the expression levels 1 and 12 h after PGF(2)alpha injection. According to the results of the molecular sub-study, no significant effect of sildenafil citrate on the mRNA expression levels in the investigated genes was detected (P > 0.05). However, within each group, differences were found according to OVH time after PGF(2)alpha injection. It was observed that PTGS2 and HPGD mRNA expressions decreased at the 12(th) h compared to the 1(st) h, while HIF1A expression increased (P < 0.05). Discussion: According to the results obtained from clinical and molecular sub-studies, it was determined that a single dose of sildenafil citrate (5 mg/kg) applied on the 3(rd) day of the luteal period did not contribute to the maturation process of the CL, did not increase blood flow, and was insufficient to break the resistance of the CL against PGF(2)alpha applied on the 4(th) day of the luteal period. However, a significant decrease in the PI value at the 40(th) min after PGF(2)alpha injection suggests that sildenafil citrate has a supportive effect, and that this decrease is also seen in the RI value, suggesting that its effect is insufficient against the vasoconstrictive effect of PGF(2)alpha.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) Project [220O076]en_US
dc.description.sponsorshipThe study was financially funded by the Scientific and Technological Research Council of Turkey (TUBITAK) Project (220O076).en_US
dc.identifier.doi10.22456/1679-9216.133456
dc.identifier.issn1678-0345
dc.identifier.issn1679-9216
dc.identifier.scopus2-s2.0-85183059332
dc.identifier.scopusqualityQ4
dc.identifier.urihttps://doi.org/10.22456/1679-9216.133456
dc.identifier.urihttps://hdl.handle.net/11468/18874
dc.identifier.volume51en_US
dc.identifier.wosWOS:001163186100001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoenen_US
dc.publisherUniv Fed Rio Grande Do Sulen_US
dc.relation.ispartofActa Scientiae Veterinariae
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectSildenafil Citrateen_US
dc.subjectPgf(2) Alphaen_US
dc.subjectCorpus Luteumen_US
dc.subjectEarly Luteal Perioden_US
dc.subjectRabbiten_US
dc.titleEarly Maturation of Corpus Luteum in Rabbits - Effect of Sildenafil Citrate on Luteolytic Capacity in the Early Luteal Perioden_US
dc.titleEarly Maturation of Corpus Luteum in Rabbits - Effect of Sildenafil Citrate on Luteolytic Capacity in the Early Luteal Period
dc.typeArticleen_US

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