Fibroblast growth factor 21 coordinates adiponectin to mediate the beneficial effects of low-protein diet on primordial follicle reserve

Abstract

Background Global consumption of protein per capita is rising, while rates of infertility are increasing. However, a clear relationship between protein intake and reproductive health has not been demonstrated. The activation of the quiescent primordial follicles is the first step of folliculogenesis, and their activation must be tightly controlled to prevent premature exhaustion of the ovarian follicular reserve. Methods The primordial follicle reserve of wild-type or liver-specific ablation of fibroblast growth factor 21 (FGF21) in mice, subjected to limited or excessive protein diets or oral gavage test, were detected in vivo. Mouse ovary organ cultures were used to examine the direct role of metabolites or metabolic hormones on primordial follicle activation. Findings Mouse primordial follicle activation, was reduced by restricted protein intake and was accelerated by excessive protein intake, in an ovarian mTORC1 signaling-dependent manner. Furthermore, restricted or excessive protein intake resulted in an augmentation or decline of oocyte number and fertility at older age, respectively. Liver-specific ablation of FGF21, which resulted in a reduction of 87% in circulating FGF21, abrogated the preserving effect of low-protein intake on primordial follicle pool. Interestingly, FGF21 had no direct effect on the activation of primordial follicles, but instead required an adipokine adiponectin. Moreover, AdipoRon, an oral adiponectin receptor agonist, prevented the over-activation effect of excessive protein intake on primordial follicle activation. Interpretation Dietary protein consumption controlled ovarian primordial follicle reserve and fertility, which required coordination between FGF21 and adiponectin. Fund (Grant 31772616).

Time‐restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21

“…The FGF21 liverspecific knockout (FGF21LKO) mice have been previously characterized. 29,35 Briefly, FGF21 loxp/loxp mice from Jackson Laboratory (022361; Bar Harbor, ME, USA) were mated with Alb-Cre mice from Nanjing University (J003574; Model Animal Research Center, Nanjing, China) to generate FGF21 loxp+/-, Alb-Cre mice. And then FGF21 loxp+/-, Alb-Cre mice were mated with FGF21 loxp/loxp mice to generate FGF21 loxp/loxp, Alb-Cre .…”

“…RNA extraction and RT-PCR were performed as previously reported. 29,35 Briefly, RNA from ovarian was extracted by Trizol (15596018; Thermo Fisher Scientific) and purified using RNA mini-columns (RR037A; Takara Bio). RT-PCR was conducted in 10 μl of reaction volume with SYBR Green (RR820A; Takara Bio).…”

Metabolomic Profiling Reveals the Difference on Reproductive Performance between High and Low Lactational Weight Loss Sows

“…In line with this, a previous study reported that the concentration of FGF21 was chronically elevated from late pregnancy to lactation in high-yielding dairy cows, which was accompanied with intense lipid mobilization [24]. Moreover, FGF-21 may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation [25,26]. In rodents, FGF21 overexpression is shown to cause infertility, such as delayed vaginal opening, reduced mating, and anovulatory hypogonadism [27].…”

Effects of Birth Weight and Postnatal Nutritional Restriction on Skeletal Muscle Development, Myofiber Maturation, and Metabolic Status of Early-Weaned Piglets

“…At the end of amplification, dissociation analyses of the PCR product were performed to confirm the specificity of PCR products. The relative mRNA abundance of analyzed genes was calculated using the method of 2 −∆∆Ct , as described previously [23]. In addition, the percentages of myosin heavy chain (MyHC) isoforms were calculated as the ratio of the normalized expression level of each MyHC isoform to the total expression of MyHC [24].…”