Abstract
Women are born with an abundant but finite pool of ovarian follicles, which naturally and progressively decreased during their reproductive years until menstrual periods stop permanently (menopause). Perimenopause represents the transition from reproductive to non-reproductive life. It is usually characterized by neuroendocrine, metabolic and behavioral changes, which result from a follicular depletion and reduced number of ovarian follicles. During this period, around 45-50 years old, women are more likely to express mood disorders, anxiety, irritability and vasomotor symptoms. The current animal models of reproductive aging do not successfully replicate human perimenopause and the gradual changes that occur in this phase. While the traditional rat model of menopause involves ovariectomy or surgical menopause consisting of the rapid and definitive removal of the ovaries resulting in a complete loss of all ovarian hormones, natural or transitional menopause is achieved by the selective loss of ovarian follicles (perimenopause period). However, the natural aging rodent (around 18-24 months) model fails to reach very low estrogen concentrations and overlaps the processes of somatic and reproductive aging. The chronic exposure of young rodents to 4-vinylcyclohexene diepoxide (VCD) is a well-established experimental model for perimenopause and menopause studies. VCD induces loss of ovarian small follicles (primary and primordial) in mice and rats by accelerating the natural process of atresia (apoptosis). The VCD, ovary-intact or accelerated ovarian failure (AOF) model is the experimental model that most closely matches natural human progression to menopause mimicking both hormonal and behavioral changes typically manifested by women in perimenopause.
Original language | English (US) |
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Article number | e3994 |
Journal | Bio-protocol |
Volume | 11 |
Issue number | 8 |
DOIs | |
State | Published - Apr 20 2021 |
Bibliographical note
Funding Information:The original study that supported this paper, “Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)” was funded by Brazilian National Council for Scientific and Technological Development (CNPq, Portuguese: Conselho Nacional de Desenvolvimento Científico e Tecnológico) and São Paulo Research Foundation (FAPESP, Portuguese: Fundação de Amparo à Pesquisa do Estado de São Paulo). This study was developed in the Laboratory of Neuroendocrinology of Female Reproduction under the guidance of Dr. Janete A Anselmo-Franci, Department of Basic and Oral Science, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Publisher Copyright:
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Keywords
- 4-vinylcyclohexene diepoxide (VCD)
- Accelerated ovarian failure (AOF)
- Chemical reproductive aging
- Follicular depletion
- Perimenopause