Maternal N-Carbamylglutamate Supplementation during Early Pregnancy Enhances Embryonic Survival and Development through Modulation of the Endometrial Proteome in Gilts.
BACKGROUND
Early pregnancy loss is a major concern in humans and animals. N-carbamylglutamate (NCG) has been found to enhance embryonic survival during early pregnancy in rats. However, little is known about the key factors in the endometrium involved in the improvement of embryonic implantation and development induced by maternal NCG supplementation.


OBJECTIVE
Our objectives were to investigate whether NCG supplementation during early gestation enhanced embryonic survival and development in gilts and to uncover the related factors using the approach of endometrium proteome analysis with isobaric tags for relative and absolute quantification (iTRAQ).


METHODS
Uteruses and embryos/fetuses were obtained on days 14 and 28 of gestation from gilts fed a basal diet that was or was not supplemented with 0.05% NCG. The iTRAQ-based quantitative proteomics approach was performed to explore the endometrium proteome altered by NCG supplementation.


RESULTS
Maternal NCG supplementation significantly increased the number of total fetuses and live fetuses on day 28 of gestation by 1.32 and 1.29, respectively (P < 0.05), with a significant decrease in embryonic mortality (P < 0.05). iTRAQ results indicated that a total of 59 proteins showed at least 2-fold differences (P < 0.05), including 52 proteins that were present at higher abundance and 7 proteins present at lower abundance in NCG-supplemented gilts. The differentially expressed proteins primarily are involved in cell adhesion, energy metabolism, lipid metabolism, protein metabolism, antioxidative stress, and immune response. On day 14 of gestation, several proteins closely related to embryonic implantation and development, such as integrin-αv, integrin-β3, talin, and endothelial nitric oxide synthase, were upregulated (3.7-, 4.1-, 2.4-, and 5.4-fold increases, respectively) by NCG supplementation.


CONCLUSIONS
To our knowledge, our results provide the first evidence that altered abundance of the endometrial proteome induced by NCG supplementation is highly associated with the improvement of embryonic survival and development in gilts.
State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, and.
Jinlong
J
Zhu
State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, and zengxf@cau.edu.cn.
Xiangfang
X
Zeng
State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, and.
Qian
Q
Peng
Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, China Agricultural University, Beijing, China; and.
Shenming
S
Zeng
Genecreate Biological Engineering Co., Ltd., National Bio-industry Base, Wuhan, China.
Haiyi
H
Zhao
Genecreate Biological Engineering Co., Ltd., National Bio-industry Base, Wuhan, China.
Hexiao
H
Shen
State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, and.
Shiyan
S
Qiao
D000596:Amino Acids / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002681:China; D003433:Crosses, Genetic; D019587:Dietary Supplements; D047108:Embryonic Development; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005327:Fetal Resorption / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D018507:Gene Expression Regulation, Developmental; D005971:Glutamates / Q000627:therapeutic use*; D008098:Litter Size; D039382:Maternal Nutritional Physiological Phenomena; D009569:Nitric Oxide / Q000097:blood; D010929:Placentation; D011247:Pregnancy; D040901:Proteomics / Q000379:methods; D011897:Random Allocation; D034421:Sus scrofa
D000596:Amino Acids; D015415:Biomarkers; D005971:Glutamates; C006895:N-carbamylglutamate; D009569:Nitric Oxide
Arg; N-carbamylglutamate; embryonic survival; gilts; iTRAQ