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Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats

  • Authors:
    • Mehmet Akif Baktir
    • Mustafa Ermis
    • Esra Balcioglu
    • Betul Yalcin
    • Enes Karaman
    • Ahmet Cumaoglu
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri 38030, Turkey, Experimental Research Application and Research Center (DEKAM), Erciyes University, Kayseri 38030, Turkey, Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri 38030, Turkey, Department of Histology and Embryology, Faculty of Medicine, Adıyaman University, Adıyaman 02040, Turkey, Department of Obstetrics and Gynecology, Faculty of Medicine, Niğde Ömer Halisdemir University, Niğde 51100, Turkey, Department of Biochemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38030, Turkey
    Copyright: © Baktir et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 11
    |
    Published online on: October 23, 2025
       https://doi.org/10.3892/mmr.2025.13721
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Abstract

A frequently occurring surgical emergency in gynecology is ovarian torsion, which occurs when the ovary twists on its ligamentous supports, which obstructs blood flow. The aim of the present study was to evaluate the protective effects of hyperbaric oxygen therapy (HBOT) and tadalafil against ischemia‑reperfusion (IR) injury in a rat model of ovarian torsion. Female Wistar albino rats were randomly assigned to five groups (n=8/group): Control, IR, IR + tadalafil, IR + HBOT and IR + tadalafil + HBOT. Ovarian torsion was induced under anesthesia for 2 h, followed by daily post‑operative treatments with tadalafil (10 mg/kg) and/or HBOT (2.4 atmospheres absolute for 1 h) for 7 days. Blood and ovarian tissue specimens were collected for analysis at the end of the treatment period. IR‑induced ovarian tissue injury significantly decreased the counts of primordial, primary and preantral follicles compared with those in the control group. In addition, serum ELISA and immunohistochemical analysis revealed that IR injury reduced anti‑Müllerian hormone (AMH) levels in serum and the granulosa cells of primary, preantral and secondary follicles. HBOT alone resulted in a significant increase in the counts of primordial, primary and preantral cells, as did the combination of HBOT with tadalafil. In addition, AMH immunoreactivity significantly increased in primary, preantral and secondary follicles following treatment with HBOT and tadalafil. Furthermore, all therapeutic interventions elevated serum AMH levels in the IR model rats. These findings suggest that tadalafil treatment combined with HBOT may help protect ovarian reserve and mitigate IR‑induced tissue damage in rat ovaries.
View Figures

Figure 1

Serum AMH levels in five groups of
rats. Data presented as mean ± SD. *P<0.05 vs. the control group
and #P<0.05 vs. the IR group. AMH, anti-Müllerian
hormone; IR, ischemia-reperfusion; HBOT, hyperbaric oxygen
therapy.

Figure 2

Immunostaining of AMH in ovarian
tissue and the semiquantitative analysis of AMH expression in
various types of ovarian follicles. Scale bar, 200 µm. Data
presented as mean ± SD. *P<0.05 vs. the control group and
#P<0.05 vs. the IR group. AMH, anti-Müllerian
hormone; IR, ischemia-reperfusion; HBOT, hyperbaric oxygen
therapy.

Figure 3

Representative MT and H&E
staining images and follicle counts of the ovarian tissues from
five groups of rats. A thick arrow indicates a primary follicle, S
indicates a secondary follicle, T indicates a tertiary follicle, O
indicates an oocyte, the thin arrow indicates a blood vessel and an
arrowhead indicates a preantral follicle. Scale bar, 200 µm. MT,
Masson's trichrome; H&E, hematoxylin and eosin; IR,
ischemia-reperfusion; HBOT, hyperbaric oxygen therapy. Data
presented as mean ± SD. *P<0.05 vs. the control group and
#P<0.05 vs. the IR group.

Figure 4

Representative TUNEL assay images and
TUNEL-positive cell counts of the ovarian tissues from five groups
of rats. Scale bar, 100 µm. IR, ischemia-reperfusion; HBOT,
hyperbaric oxygen therapy. The assay was repeated three times. Data
presented as mean ± SD. *P<0.05 vs. the control group.
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Copy and paste a formatted citation
Spandidos Publications style
Baktir MA, Ermis M, Balcioglu E, Yalcin B, Karaman E and Cumaoglu A: Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats. Mol Med Rep 33: 11, 2026.
APA
Baktir, M.A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., & Cumaoglu, A. (2026). Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats. Molecular Medicine Reports, 33, 11. https://doi.org/10.3892/mmr.2025.13721
MLA
Baktir, M. A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., Cumaoglu, A."Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats". Molecular Medicine Reports 33.1 (2026): 11.
Chicago
Baktir, M. A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., Cumaoglu, A."Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats". Molecular Medicine Reports 33, no. 1 (2026): 11. https://doi.org/10.3892/mmr.2025.13721
Copy and paste a formatted citation
x
Spandidos Publications style
Baktir MA, Ermis M, Balcioglu E, Yalcin B, Karaman E and Cumaoglu A: Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats. Mol Med Rep 33: 11, 2026.
APA
Baktir, M.A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., & Cumaoglu, A. (2026). Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats. Molecular Medicine Reports, 33, 11. https://doi.org/10.3892/mmr.2025.13721
MLA
Baktir, M. A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., Cumaoglu, A."Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats". Molecular Medicine Reports 33.1 (2026): 11.
Chicago
Baktir, M. A., Ermis, M., Balcioglu, E., Yalcin, B., Karaman, E., Cumaoglu, A."Combining tadalafil and hyperbaric oxygen therapy protects against ovarian ischemia‑reperfusion damage in rats". Molecular Medicine Reports 33, no. 1 (2026): 11. https://doi.org/10.3892/mmr.2025.13721
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