Abstract

BackgroundIn developing countries, maternal undernutrition is the major intrauterine environmental factor contributing to fetal development and adverse pregnancy outcomes. Maternal nutrition restriction (MNR) in gestation has proven to impact overall growth, bone development, and proliferation and metabolism of mesenchymal stem cells in offspring. However, the efficient method for elucidation of fetal bone development performance through maternal bone metabolic biochemical markers remains elusive.MethodsWe adapted goats to elucidate fetal bone development state with maternal serum bone metabolic proteins under malnutrition conditions in mid- and late-gestation stages. We used the experimental data to create 72 datasets by mixing different input features such as one-hot encoding of experimental conditions, metabolic original data, experimental-centered features and experimental condition probabilities. Seven Machine Learning methods have been used to predict six fetal bone parameters (weight, length, and diameter of femur/humerus).ResultsThe results indicated that MNR influences fetal bone development (femur and humerus) and fetal bone metabolic protein levels (C-terminal telopeptides of collagen I, CTx, in middle-gestation and N-terminal telopeptides of collagen I, NTx, in late-gestation), and maternal bone metabolites (low bone alkaline phosphatase, BALP, in middle-gestation and high BALP in late-gestation). The results show the importance of experimental conditions (ECs) encoding by mixing the information with the serum metabolic data. The best classification models obtained for femur weight (Fw) and length (FI), and humerus weight (Hw) are Support Vector Machines classifiers with the leave-one-out cross-validation accuracy of 1. The rest of the accuracies are 0.98, 0.946 and 0.696 for the diameter of femur (Fd), diameter and length of humerus (Hd, Hl), respectively. With the feature importance analysis, the moving averages mixed ECs are generally more important for the majority of the models. The moving average of parathyroid hormone (PTH) within nutritional conditions (MA-PTH-experim) is important for Fd, Hd and Hl prediction models but its removal for enhancing the Fw, Fl and Hw model performance. Further, using one feature models, it is possible to obtain even more accurate models compared with the feature importance analysis models. In conclusion, the machine learning is an efficient method to confirm the important role of PTH and BALP mixed with nutritional conditions for fetal bone growth performance of goats. All the Python scripts including results and comments are available into an open repository at https://gitlab.com/muntisa/goat-bones-machine-learning.

Highlights

  • In the early stages of embryonic development of mammals, the fetal skeleton development is composed of fibrous membranes and hyaline cartilage

  • The bone is usually formed through endochondral ossification and intramembranous ossification regulated by intra- or extra-factors in the middle or late gestation

  • The mineral metabolism of fetus skeletal development is essentially dependent on parathyroid hormone (PTH), and PTH-related proteins (PTHrP) (Mendes et al, 2019), but not calcitonin, vitamin D/calcitriol, fibroblast growth factor (FGF-23) or sex steroids (Kovacs, 2015)

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Summary

Introduction

In the early stages of embryonic development of mammals, the fetal skeleton development is composed of fibrous membranes and hyaline cartilage. The most commonly measured bone formation biomarkers are the bone alkaline phosphatase (BALP) and its isoforms, osteocalcin (OC) (Lee et al, 2007), and the procollagenbreakdown products (procollagen type 1 N-terminal and C-terminal propeptides, PICP and PINP). The efficient method for elucidation of fetal bone development performance through maternal bone metabolic biochemical markers remains elusive. We adapted goats to elucidate fetal bone development state with maternal serum bone metabolic proteins under malnutrition conditions in mid- and lategestation stages. Seven Machine Learning methods have been used to predict six fetal bone parameters (weight, length, and diameter of femur/humerus). The results indicated that MNR influences fetal bone development (femur and humerus) and fetal bone metabolic protein levels (C-terminal telopeptides of collagen I, CTx, in middle-gestation and N-terminal telopeptides of collagen I, NTx, in lategestation), and maternal bone metabolites (low bone alkaline phosphatase, BALP, in middle-gestation and high BALP in late-gestation). Using one feature models, it is possible to obtain

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