Exome-informed formulations of food proteins enhance body growth and feed conversion efficiency in ad libitum-fed mice.

Meeting requirements for dietary proteins, especially of essential amino acids (EAAs), is critical for the life-long health of living organisms. However, defining EAA targets for preparing biologically-matched nutrition that satisfies metabolic requirements for protein remains challenging. Previous research has shown the advantages of 'exome matching' in representing the specific requirement of dietary AAs, where the target dietary AA profile was derived from in silico translation of the genome of an organism, specifically responsible for protein expression (the 'exome'). However, past studies have assessed these effects in only one sex, for few parameters (body mass and composition), and have used purified diets in which protein is supplied as a mixture of individual AAs. Here, for the first time, we utilise a computational method to guide the formulation of custom protein blends and test if exome matching can be achieved at the intact protein level, through blending standard protein ingredients, ultimately leading to optimal growth, longevity and reproductive function. Mice were provided ad libitum (ad lib) access to one of the four iso-energetic protein-limited diets, two matched and two mis-matched to the mouse exome target, and fed at a fixed protein energy level of 6.2%. During or following 13-weeks of feeding, the food intake, body growth, composition and reproductive functions were measured. Compared to the two mis-matched diets, male and female animals on the exome-matched diet with protein digestibility correction applied, exhibited significantly improved growth rates and final body mass. The feed conversion efficiency in the same diet was also increased by 62% and 40% over the worst diets for males and females, respectively. Male, not female, exhibited higher accretion of lean body mass with the matched, digestibility-corrected diet. All reproductive function measures in both sexes were comparable among diets, with the exception of testicular daily sperm production in males, which was higher in the two matched diets versus the mis-matched diets. The results collectively demonstrate the pronounced advantages of exome-matching in supporting body growth and improving feed conversion efficiency in both sexes. However, the potential impact of this approach in enhancing fertility needs further investigation.

Multidose 5-Fluorouracil is Highly Toxic to Growing Ovarian Follicles in Mice.

With increasing improvements in cancer survival rates, it is critical to reduce the significant long-term side effects that afflict patients following treatment. For women, consequences of chemotherapy-induced damage to the reproductive system include infertility and premature menopause, which adversely effects cognition, mood, cardiovascular, bone, and sexual health, and increases the risk of early mortality. These long-term effects impact patient's life quality and highlight a significant and on-going burden on the health system after treatment. However, the precise mechanisms through which chemotherapeutic agents induce ovarian damage and primordial follicle depletion remain to be characterized. Hence, preventing the development of effective pharmacological methods to preserve fertility and improve quality of life after treatment. The chemotherapeutic agent 5-Fluorouracil (5FU) is not deemed cytotoxic to the ovary, however, risks to long-term fertility after multiple doses are not known. Therefore, we sought to evaluate the impact of 3, weekly doses of 5FU treatment on the ovary. Using a mouse model enabled accurate histomorphometric analysis of follicle numbers and ovarian structure and function, to accurately assess cumulative impact of 5FU on the ovary. This study clearly demonstrated that multidose 5FU treatment resulted in dramatic and progressive atresia of growing follicles and a profound decrease in ovarian volume due to reduced corpus luteum counts. However, primordial follicle numbers were unaffected. Thus, 5FU is unlikely to cause permanent infertility when administered to women of pre or reproductive age. Furthermore, this study suggests that depletion of the growing follicle population is insufficient to stimulate follicle activation and primordial follicle depletion.