Endocrine profile of the VCD-induced perimenopausal model rat

PLoS One. 2019 Dec 30;14(12):e0226874. doi: 10.1371/journal.pone.0226874. eCollection 2019.

Abstract

During the transition to menopause, women experience a variety of physical and psychological symptoms that are directly or indirectly linked to changes in hormone secretion. Establishing animal models with intact ovaries is essential for understanding these interactions and finding new therapeutic targets. In this study, we assessed the endocrine profile, as well as the estrous cycle, in the 4-vinylcyclohexene diepoxide (VCD)-induced follicular depletion rat model in 10-day intervals over 1 month to accurately establish the best period for studies of the transition period. Twenty-eight-day-old female rats were injected daily with VCD or oil s.c. for 15 days and euthanized in the diestrus phase approximately 70, 80, 90 and 100 days after the onset of treatment. The percentage of rats showing irregular cycles and the plasma level of FSH increased only in the 100-day VCD group. Plasma anti-Müllerian hormone (AMH) and progesterone were lower in all VCD groups compared to control groups, while estradiol remained unchanged or higher. As in control groups, dihydrotestosterone (DHT) progressively decreased in the 70-90-day VCD groups; however, it was followed by a sharp increase only in the 100-day VCD group. No changes were found in plasma corticosterone, prolactin, thyroid hormones or luteinizing hormone. Based on the estrous cycle and endocrine profile, we conclude that 1) the time window from 70 to 100 days is suitable to study a perimenopause-like state in this model, and 2) regular cycles with low progesterone and AMH and normal FSH can be used as markers of the early/mid-transition period, whereas irregular cycles associated with higher FSH and DHT can be used as markers of the late transition period to estropause.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Mullerian Hormone / blood
  • Biomarkers / blood
  • Cyclohexenes
  • Dihydrotestosterone / blood
  • Endocrine System / chemistry*
  • Estrous Cycle / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Models, Animal
  • Perimenopause / blood*
  • Progesterone / blood
  • Rats
  • Time Factors
  • Vinyl Compounds

Substances

  • Biomarkers
  • Cyclohexenes
  • Vinyl Compounds
  • Dihydrotestosterone
  • Progesterone
  • 4-vinyl-1-cyclohexene dioxide
  • Anti-Mullerian Hormone
  • Follicle Stimulating Hormone

Grants and funding

This work was supported by a grant from Foundation for Research Support of the State of Sao Paulo – FAPESP and by CAPES/PROEX (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior-Brazil; Finance Code 001). JAAF is supported by the National Council of Scientific and Technological Development (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.