J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 110-116, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1512_11.1.110

Original Article

Epithelial thinning in vaginal atrophy related to lowering of calcitonin gene-related protein, vascular endothelial growth factor, and nerve growth factor expressions in a menopausal rat model

[Adelgazamiento epitelial en la atrofia vaginal relacionado con la disminución de las expresiones de la proteína relacionada con el gen de la calcitonina, el factor de crecimiento endotelial vascular y el factor de crecimiento nervioso en un modelo de rata menopáusica]

An Nisa Fithri^1,2*, Yuyun Yueniwati³, I Wayan Arsana⁴, Husnul Khotimah⁵, Wiwit Nurwidyaningtyas⁶

¹Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Indonesia.

²Midwifery Program, Sekolah Tinggi Ilmu Kesehatan Kendedes Malang, 65126, Indonesia.

³Department of Radiology, Public Saiful Anwar Hospital, Malang, Indonesia,

⁴Department of Fertility, Endocrinology and Reproduction, Obstetric and Gynecology Laboratory, Public Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Indonesia.

⁵Department of Pharmacology, Universitas Brawijaya, Indonesia.

⁶Department Molecular and Cellular Biology, Sekolah Tinggi Ilmu Kesehatan Kendedes, Malang, 65126, Indonesia.

*E-mail: teh.nisa1@gmail.com

Abstract

Context: Vaginal atrophy has been observed as a common sexual problem in post-menopausal women. The targeted protein to counteract menopause problems related to vaginal epithelial thinning is currently a research problem that has not been fully investigated.

Aims: To explore the possible mechanism underlying vaginal atrophy in rat models.

Methods: Following three-week ovariectomy (OVX), Sprague-Dawley female rats were randomly divided into two groups and orally administered estradiol for two weeks in the treated group. In parallel with this, six rats with sham surgery were used as control. Marker-related vaginal atrophy, including calcitonin gene-related protein (CGRP), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) in the vaginal wall, were compared using immunohistochemistry.

Results: OVX as a menopausal model significantly induced vaginal epithelial cell thinning and decreased the expression of CGRP, VEGF, and NGF compared with sham surgery animals (p<0.05). Estrogen replacement in OVX rats reversed the vaginal atrophic by recovering the protein expression CGRP, VEGF, and NGF (p<0.05).

Conclusions: Thus, it may be concluded that a possible mechanism underlying the OVX-induced vaginal atrophy may be related to the downregulation expression of CGRP, VEGF, and NGF in vaginal tissue.

Keywords: calcitonin gene-related protein; menopause; nerve growth factor; ovariectomy model; vaginal atrophy; vascular endothelial growth factor.

Resumen

Contexto: Se ha observado que la atrofia vaginal es un problema sexual común en las mujeres posmenopáusicas. La proteína dirigida a contrarrestar los problemas de la menopausia relacionados con el adelgazamiento del epitelio vaginal es actualmente un problema de investigación que no se ha investigado completamente.

Objetivos: Explorar el posible mecanismo subyacente a la atrofia vaginal en modelos de rata.

Métodos: Tras una ovariectomía (OVX) de tres semanas, se dividieron aleatoriamente ratas hembras Sprague-Dawley en dos grupos y se les administró estradiol por vía oral durante dos semanas en el grupo tratado. Paralelamente, se utilizaron como control seis ratas con cirugía simulada. Se compararon mediante inmunohistoquímica los marcadores de atrofia vaginal, como la proteína relacionada con el gen de la calcitonina (CGRP), el factor de crecimiento endotelial vascular (VEGF) y el factor de crecimiento nervioso (NGF) en la pared vaginal.

Resultados: La OVX como modelo menopáusico indujo significativamente el adelgazamiento de las células epiteliales vaginales y disminuyó la expresión de CGRP, VEGF y NGF en comparación con los animales sometidos a cirugía simulada (p<0,05). El reemplazo de estrógenos en las ratas OVX revirtió la atrofia vaginal recuperando la expresión de proteínas CGRP, VEGF y NGF (p<0,05).

Conclusiones: Por lo tanto, se puede concluir que un posible mecanismo subyacente a la atrofia vaginal inducida por la OVX puede estar relacionado con la disminución de la expresión de CGRP, VEGF y NGF en el tejido vaginal.

Palabras Clave: atrofia vaginal; factor de crecimiento endotelial vascular; factor de crecimiento nervioso; ; menopausia; modelo de ovariectomía; proteína relacionada con el gen de la calcitonina.

Citation Format: Fithri AN, Yueniwati Y, Arsana IW, Khotimah H, Nurwidyaningtyas W (2023) Epithelial thinning in vaginal atrophy related to lowering of calcitonin gene-related protein, vascular endothelial growth factor, and nerve growth factor expressions in a menopausal rat model. J Pharm Pharmacogn Res 11(1): 110–116. https://doi.org/10.56499/jppres22.1512_11.1.110

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