Pseudo-Starvation Driven Energy Expenditure Negatively Affects Ovarian Follicle Development

Abstract

In the present investigation, we examined whether a change in whole body energy fluxes could affect ovarian follicular development, employing mice ectopically expressing uncoupling protein 1 in skeletal muscle (UCP1-TG). Female UCP1-TG and wild-type (WT) mice were dissected at the age of 12 weeks. Energy intake and expenditure, activity, body weight and length, and body composition were measured. Plasma insulin, glucose, leptin, plasma fibroblast growth factor 21 (FGF21) and plasma insulin-like growth factor 1 (IGF1) levels were analyzed and ovarian follicle and corpus luteum numbers were counted. IGF1 signaling was analyzed by immunohistochemical staining for the activation of insulin receptor substrate 1/2 (IRS1/2) and AKT. UCP1-TG female mice had increased energy expenditure, reduced body size, maintained adiposity, and decreased IGF1 concentrations compared to their WT littermates, while preantral and antral follicle numbers were reduced by 40% and 60%, respectively. Corpora lutea were absent in 40% of the ovaries of UCP1-TG mice. Phospho-IRS1, phospho-AKT -Ser473 and -Thr308 immunostaining was present in the granulosa cells of antral follicles in WT ovaries, but faint to absent in the antral follicles of UCP1-TG mice. In conclusion, the reduction in circulating IGF1 levels due to the ectopic expression of UCP1 is associated with reduced immunostaining of the IRS1-PI3/AKT pathway, which may negatively affect ovarian follicle development and ovulation.

Umbilical Cord Mesenchymal Stem Cells Ameliorate Premature Ovarian Insufficiency in Rats

“…In every fifth ovarian section, primary, secondary, and antral follicles were counted when the oocyte with nucleus and nucleolus was present in the follicular cross section. Primordial follicles were also counted every fifth section when the oocyte with multiple nucleoli was visible in the follicular cross section [ 31 ]. The distribution of ovarian follicular development was evaluated under an optical microscope (DM3000LED, Leica, Germany).…”

Prolonged fasting induces significant germ cell loss in chickens after hatching

“…Activation of autophagy promotes primordial follicles formation in mice ( Watanabe and Kimura, 2018 ; Sun et al, 2020 ; Watanabe et al, 2020 ). Interestingly, previous studies showed opposite results, that is, starvation negatively affects mouse oocyte development ( Wang et al, 2017 ; Meng et al, 2021 ). Our results showed that early-stage fasting in chickens may lead to an increase in germ cell loss.…”

“…Newborn animals commonly experience fasting, and mice have been shown to adapt their metabolic and oxidative responses in the ovaries leading to an increase in apoptosis of somatic cells and oocytes due to nutrient deficiency at birth ( Wang et al, 2017 ). In addition, whole body energy fluxes may have adverse effects on ovarian follicle development and ovulation ( Meng et al, 2021 ). Conversely, chicks given early access to feed and water may compensate for the developmental disadvantage experienced at hatching ( van de Ven et al, 2013 ).…”

“…Moreover, under these conditions, the chicks experience germ cell nest breakdown. In mice, a reduced body energy balance may negatively affect ovarian follicle development ( Meng et al, 2021 ), and starvation after birth also reduces germ cell nest breakdown and increases apoptosis of ovarian follicles ( Wang et al, 2017 ). Whether starvation at early life history stages affects germ cell loss in chicks is unclear.…”