Endocrine profile of the VCD-induced perimenopausal model rat

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.

Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation

“…In a recently published article, Carolino and colleagues studied the endocrine profile of POI rats induced by VCD. They reported that the FSH levels in POI rats did not significantly change for at least 90 days after the VCD administration [50]. In another study, VCD did not influence the FSH levels until 240 days from the start of the experiment [24], and Mayer and colleagues reported that VCD injection to mice do not significantly increase the FSH levels until 37 days [27].…”

Follicle-Stimulating Hormone Positively Associates with Metabolic Factors in Perimenopausal Women

“…Perimenopause is the transition period from the reproductive to the nonreproductive stage of life, with important changes in their hormone, including FSH and estrogen [ 12 ]. Women may experience a number of symptoms associated with the menopausal transition, including vasomotor symptoms, vaginal dryness, sleeping disorders, and the onset of depression [ 13 ], and menopause transition was also associated with adverse health indicators, such as increased TC and LDL-C levels, increased cardiovascular risk and a greater bone loss/increased bone turnover [ 14 – 16 ].…”

Development of a Chemical Reproductive Aging Model in Female Rats

“…women have a typical hormonal profile, with reduction in progesterone plasma concentrations while estradiol concentrations are normal or erratically high (Santoro et al, 1996;Prior and Hitchcock, 2011). The same pattern was observed in rats submitted to chronic VCD injections (Reis et al, 2014;Pestana-Oliveira et al, 2018;Carolino et al, 2019). Therefore, we consider this an effective way to assess whether perimenopause was induced in female rats.…”

“…Note: The collection of the vaginal smear and evaluation of the estrous cycle must be carried out in the early morning, between 7:30 and 9:30 am to prevent the cells present in the vaginal fluid from moving from one phase to the next. Since until close to 90 days after the onset of VCD treatment the proportion of rats that cycle regularly (about 20%) is the same in control rats and those treated with VCD (Carolino et al, 2019). Only control and VCD treated rats cycling regularly be used in the experiments performed before 90 days after starting VCD injections.…”

“…Importantly, the VCD model or model of Accelerated Ovarian Failure (AOF, Brooks et al, 2016) mimic both hormonal (Reis et al, 2014;Pestana-Oliveira et al, 2018;Carolino et al, 2019) and behavioral changes such as anxiety (Reis et al, 2014), impaired memory (Koebele et al, 2016), depression (Kalil et al, 2020) and aggressiveness (Dalpogeto et al, 2016;Scafuto et al, 2017) women in perimenopause. Low doses of VCD specifically cause selective destruction of ovarian small pre-antral follicles without affecting other peripheral tissues.…”