Figures
Abstract
Low birth weight may negatively affect energy storage and nutrient metabolism, and impair fetal growth and development. We analyzed effects of body weight (BW) and gestational period on nutrient composition in fetal Huanjiang mini-pigs. Fetuses with the lowest BW (LBW), middle BW (MBW), and highest BW (HBW) were collected at days 45, 75, and 110 of gestation. Crude protein (CP), crude fat, amino acid (AA), and fatty acid (FA) concentrations were determined. The BW gain, carcass weight, fat percentage, and uterus weight of sows increased as gestation progressed, as did litter weight, average individual fetal weight, fetal body weight, and dry matter (DM). The concentrations of Ala, Arg, crude fat, Gly, Pro, Tyr, C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, saturated FA (SFA), and monounsaturated FA (MUFA) increased significantly as gestation progressed. The percentage of skeleton, and the ratio of the liver, lung, and stomach to BW decreased as gestation progressed. There were also significant reductions in the concentrations of CP, Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, essential AA (EAA), acidic AA, C17:0, C20:4n6, C22:6n3, unsaturated FA (UFA), polyunsaturated FA (PUFA), n-3PUFA, n-6PUFA as gestation progressed, and reductions in EAA/total AA (TAA), PUFA/SFA, and n-3/n-6 PUFA. The LBW fetuses exhibited the lowest BW and crude fat, C14:0, C16:1, C17:0, C18:2n6c, and MUFA concentrations at days 75 and 110 of gestation. They also exhibited lower Tyr concentration at day 45 of gestation and lower Glu concentration at day 75 of gestation than HBW fetuses. These findings suggest that LBW fetuses exhibit lower amounts of crude fat and several FAs during mid-gestation and late-gestation, which may in turn affect adaptability, growth, and development.
Citation: Zhu Q, Xie P, Li H, Ma C, Zhang W, Yin Y, et al. (2018) Fetal Huanjiang mini-pigs exhibit differences in nutrient composition according to body weight and gestational period. PLoS ONE 13(7): e0199939. https://doi.org/10.1371/journal.pone.0199939
Editor: Juan J. Loor, University of Illinois, UNITED STATES
Received: March 19, 2018; Accepted: June 15, 2018; Published: July 13, 2018
Copyright: © 2018 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information file.
Funding: The present work was jointly supported by the National Natural Science Foundation of China (no. 31572421 and 31772613).
Competing interests: The authors have declared that no competing interests exist.
Introduction
In swine production facilities, approximately 15–20% of newborn piglets exhibit low birth weight [1, 2]. This low birth weight may lead to lower rates of survival, slower postnatal growth, suboptimal carcass quality, lower efficiency of nutrient utilization, and an increase in the number of days required to reach the common slaughter weight [3–5]. Low birth weight is caused by intrauterine growth retardation (IUGR) during gestation [6]. In general, fetal body weight (BW) that is more than two standard deviations below the mean BW at the corresponding gestational age is considered indicative of IUGR [7, 8]. Pigs are multifetal domestic animals and frequently exhibit IUGR.
Fetal growth is affected by the nutritional, metabolic, and endocrine status of the maternal system [9]. Maternal under-nutrition or over-nutrition may result in IUGR [1] that negatively affects the metabolism, growth, and development of fetal pigs, as well as numerous metabolic pathways and their feeding efficiency and disease susceptibility [10]. Despite advances in nutrition and management techniques, low birth weight and substantial litter variation in fetal weight frequently occur during the late gestational phase, and the precise mechanisms underlying fetal pig development remain to be fully elucidated.
Huanjiang mini-pigs are anatomically and physiologically similar to humans, and their relatively small size makes them easier to handle than other varieties of pigs [11–13]. In addition, they are the most popular local pigs in Guangxi, China. Dietary nutrients play important roles during gestation, and the feeding management and feed intake can affect maternal reproductive performance and fetal growth and development [14]. Huanjiang mini-pigs are usually grazed and fed diets with lower nutrient level or with imbalanced nutrition, and have lower body weight at the first service and bigger litter size. Therefore, these various characteristics of Huanjiang mini-pigs render them more susceptible to low birth weight. Therefore, Huanjiang mini-pigs were considered an appropriate experimental model.
The growth rates of fetal pigs vary over the course of gestation, accelerating during the second half of pregnancy [15]. As the body composition of fetal pigs may vary in conjunction with growth rates, the present study aimed to analyze nutrient composition in fetal Huanjiang mini-pigs in terms of BW and gestational period. We also aimed to determine whether fetal pigs with different BWs exhibited differences in body composition, as well as the time at which these potential differences occurred, in order to provide a theoretical basis for developing nutritional interventions targeting fetuses with low birth weight.
Materials and methods
All pigs used in the present study were managed in accordance with the Chinese Guidelines for Animal Welfare. The experimental design and procedures were reviewed and approved by the Animal Care and Use Committee of the Institute of Subtropical Agriculture, Chinese Academy of Science, China.
Animals, diets, and treatments
The present study was conducted at the Mini-pig Research Center at the Huanjiang Observation and Research Station for Karst Ecosystems in Huanjiang, Guangxi, China. A total of 24 primiparous Huanjiang mini-pigs with an initial BW of approximately 30 kg were obtained from a mini-pig farm located in Jixiang, Huanjiang, Guangxi Province, China (108°27'40.8" E, 25°9'50" N) and reared in eight pens, with three mini-pigs per pen. The animals were fed a diet formulated in accordance with the recommendations of the Chinese National Feeding Standard for Swine (Table 1), which is commonly used in commercial Huanjiang mini-pig farms. Animals were allowed access to water ad libitum for the duration of the experiment. The animals were fed at 8:00, 15:00, and 18:00 each day, and the quantity of each feed was approximately 2% of maternal BW.
Sample collection
Sows were fasted and weighed at days 45, 75, and 110 of gestation. One sow per pen was randomly selected and sacrificed under commercial conditions via electrical stunning (120 V, 200 Hz) and exsanguination [16], after which each sow was dissected, and its uterus and fetuses were each individually weighed. The size of each fetus was recorded. The carcass, muscle, fat, skeleton, liver, lungs, and stomach were dissected and weighed to determine the percentages of live BW (tissue weight [kg]/BW [kg] × 100%) or ratio to live BW (organ weight [g]/BW [kg]) that they comprised. Fetuses with the lowest, middle (similar to mean BW), and highest BW (LBW, MBW, and HBW, respectively) in each litter were dissected and their internal organs were removed. The remaining fetuses were stored in sealed plastic bags at -80°C prior to further analysis.
Determination of dry matter, crude protein, and crude fat
The fetal pigs were minced after weighing and dried in a vacuum-freeze dryer (CHRIST RVC2-25 CDPIUS; Christ Company, Osterode, Germany) in order to calculate the dry matter (DM) concentration. The crude protein (CP) concentration (N × 6.25) was determined using the Kjeldahl method in accordance with standards provided by the Association of Official Analytical Chemists [17]. The crude fat concentration was determined using the Soxhlet extraction method. Petroleum ether was used as the binary extracting solution [18].
Determination of hydrolyzed amino acids
Approximately 0.1000 g of freeze-dried fetal pig powder was hydrolyzed in 10 mL of 6 mol/L hydrochloric acid solution at 110°C for 24 h. The suspension was diluted to 100 mL in double-distilled water [19], then 1 mL of supernatant was transferred to a 1.5-mL centrifuge tube and evaporated to dryness in a water bath at 65°C. The sample was then dissolved using 1 mL of 0.02 mol/L hydrochloric acid solution and filtered through a 0.45-μm membrane prior to analysis [20] with an ion-exchange AA analyzer (L8800, Hitachi, Tokyo, Japan).
Determination of fatty acids
Different fatty acids (FAs) were identified via gas-liquid chromatography (7890A, Agilent, California, USA) of methyl esters as previously described [21, 22]. The FA composition was expressed as g/100 g of total identified FA. The following parameters were calculated based on the FA composition: the sum of saturated FA (SFA, C14:0 + C16:0 + C17:0 + C18:0 + C20:0); unsaturated FA (UFA, C16:1 + C18:1n9c + C18:1n9t + C18:2n6c + C18:3n3 + C18:3n6 + C20:1 + C20:3n6 + C20:4n6 + C22:6n3); monounsaturated FA (MUFA, C16:1 + C18:1n9c + C18:1n9t + C20:1); polyunsaturated FA (PUFA, C18:2n6c + C18:3n3 + C18:3n6 + C20:3n6 + C20:4n6 + C22:6n3); n-3PUFA (C18:3n3 + C18:3n6 + C22:6n3); n-6 PUFA (C18:2n6c + C20:3n6 + C20:4n6); and the ratios of PUFA to SFA and n-6 to n-3 PUFA.
Statistical analysis
Sow data were analyzed via one-way analysis of variance. Fetal data were analyzed using a mixed-effects model, and the means were separated using Tukey’s method. Analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC, USA). Results are presented as means and standard errors of the mean. Gestational periods, BWs, and their interactions were included in the statistical model. The level of statistical significance was set at P < 0.05. Probability values between 0.05 and 0.10 were considered indicative of trends.
Results
Reproductive performance of sows
The reproductive performance of sows is presented in Table 2. Uterus weight, litter weight, and average individual fetal weight increased (P < 0.05) as gestation progressed.
Body composition and organ ratio of sows
The body composition and organ ratios of sows are shown in Table 3. As gestation progressed, both BW and carcass weight increased (P < 0.05), and fat percentage tended to increase (P = 0.074). Skeleton percentage and the ratio of the liver, lung, and stomach to total BW decreased (P < 0.05), and muscle percentage tended to decrease (P = 0.070).
Body weight of fetal pigs
Table 4 presents the fetal BWs, which increased as gestation progressed (P < 0.05). The BWs of HBW fetuses were significantly higher than those of LBW fetuses at day 110 of gestation (P < 0.05), but not at days 45 or 75 of gestation. A trend (P = 0.072) was observed with regard to interaction between gestation period and fetal BW.
Dry matter, crude protein, and crude fat concentrations of fetal pigs
The DM, CP, and crude fat concentrations of fetal pigs are shown in Table 4. DM and crude fat concentrations increased (P < 0.05) in fetuses with LBW, MBW, and HBW as gestation progressed, while CP concentration in fetuses with MBW and HBW decreased (P < 0.05). No significant differences (P > 0.05) in DM or CP concentrations were observed in fetuses with LBW, MBW, or HBW at any of the three different gestation periods. In addition, no significant differences in crude fat concentration were observed at day 45 of gestation. At day 75 of gestation, crude fat concentration was higher (P < 0.05) in HBW fetuses than in MBW or LBW fetuses. At day 110 of gestation, crude fat concentration in MBW and HBW fetuses was higher (P < 0.05) than that of LBW fetuses. Interaction effects (P < 0.05) were observed between gestation period and BW with regard to DM, CP, and crude fat concentrations.
Amino acid composition of fetal pigs
The amino acid (AA) composition of fetal pigs is shown in Table 5. As gestation progressed, the Ala, Arg, Gly, Pro, and Tyr concentrations of fetuses with LBW, MBW, and HBW increased (P < 0.05), while the concentrations of Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, and essential AA (EAA) decreased (P < 0.05). We also observed a significant decrease in the ratio of EAA/(total AA) TAA. Significant decreases (P < 0.05) in TAA concentration were observed in MBW and LBW fetuses as gestation progressed. The Cys and Val concentrations in fetuses with LBW, MBW, and HBW tended to decrease and then increase (P < 0.05) as gestation progressed, and a similar pattern was observed for TAA and non-essential AA (NEAA) in HBW fetuses.
Relative to levels observed in HBW fetuses, Tyr and NEAA concentrations were higher (P < 0.05) in LBW fetuses at day 45 of gestation, while Glu concentration was higher at day 75 of gestation. The TAA and EAA concentrations were also higher (P < 0.05) in MBW fetuses at day 75 of gestation, while NEAA concentration was higher (P < 0.05) in MBW and LBW fetuses at days 75 and 110 of gestation, relative to levels observed in HBW fetuses.
Significant effects (P < 0.05) of gestation period × BW were observed on Tyr, EAA, and TAA concentrations in fetal pigs. A similar trend (P = 0.09) was observed for gestation period × BW interaction on Gly concentration.
Fatty acid composition of fetal pigs
The FA composition of fetal pigs is shown in Table 6. As gestation progressed, significant increases (P < 0.05) in C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, SFA, and MUFA concentrations were observed in fetuses with LBW, MBW, and HBW, and significant decreases in C17:0, C20:4n6, C22:6n3, UFA, PUFA, n-3PUFA, and n-6PUFA concentrations were observed, along with corresponding significant decreases in PUFA/SFA and n-3/n-6PUFA (P < 0.05). C18:0, C18:1n9t, and C20:1 concentrations first decreased and then increased (P < 0.05) in fetuses with LBW, MBW, and HBW as gestation progressed.
At day 45 of gestation, n-3PUFA concentration was higher (P < 0.05) in MBW fetuses than in HBW fetuses. At day 75 of gestation, C14:0 and C16:0 concentrations were higher (P < 0.05) in MBW fetuses than in LBW fetuses. In addition, C17:0 concentration was higher (P < 0.05) in MBW and HBW fetuses, while C20:4n6, C20:6n3, and PUFA concentrations were lower (P < 0.05) in HBW fetuses than in LBW fetuses. C18:0 concentration was higher (P < 0.05) in HBW fetuses than in MBW fetuses at day 75 of gestation. At day 110 of gestation, C18:0 and n-3PUFA concentrations were higher (P < 0.05) in LBW fetuses than in HBW fetuses. The concentrations of C20:4n6, C20:6n3, and PUFA were higher (P < 0.05) in MBW and LBW fetuses, while MUFA concentration was lower (P < 0.05) than that of HBW fetuses. C14:0 and C16:1 concentrations were higher (P < 0.05) in MBW and HBW fetuses, while the n-3/n-6PUFA ratio was lower (P < 0.05) than that of LBW fetuses. C18:2n6c concentration was lower (P < 0.05) in LBW fetuses than it was in both MBW and HBW fetuses.
Significant interaction effects (P < 0.05) were observed between gestation period and BW with regard to C14:0, C16:1, C17:0, C18:0, C18:2n6c, C20:4n6, C22:6n3, MUFA, PUFA, and n-6PUFA concentrations. Trend-level interaction effects of gestation period × BW were observed on n-3PUFA (P = 0.072), PUFA/SFA (P = 0.09), and n-3/n-6PUFA (P = 0.061).
Discussion
The present study aimed to determine the changes in the nutrient composition of fetuses according to BW and gestation period using Huanjiang mini-pig models. LBW fetuses exhibited lower amounts of crude fat and several FAs at mid-gestation and late-gestation, which may in turn affect adaptability, growth, and development.
During gestation, sows undergo dramatic changes and must acquire enough nutrition to maintain their own health and development and that of their fetuses. An improper supply of nutrition will negatively affect the health of sows as well as fetal growth and development [23]. In the present study, uterus weight, litter weight, and average individual fetal weights increased as gestation progressed, mainly due to continuous growth and development of the fetuses. However, no significant difference in fetus number was observed between days 45, 75, and 110 of gestation. This is likely because of the 20–45% of conceptuses lost throughout gestation, most are lost between 12 and 30 days after conception [24].
Maximal fetal growth occurs during the third trimester of pregnancy, during which sows must increase their nutrient intake to meet the demands of the growing fetuses [25]. Therefore, changes in the body composition of sows may reflect the utilization of the body’s nutrient reserves. In the present study, the BW gain and carcass weight of sows increased as gestation progressed, due to the continued growth of the mother and her conceptuses, and previous studies have indicated that maternal fluid expansion throughout pregnancy contributes to such increases [26]. We also observed that body fat percentage tended to increase as gestation progressed, which is beneficial to fetal growth. The percentage of muscle and the ratio of liver, lung, and stomach to BW decreased as gestation progressed, due to the rapid increase in the size of the conceptuses.
Fetal growth and development is influenced by several factors including genetics, epigenetics, maternal maturity, maternal nutrition during gestation, uterine capacity, placental efficiency, litter size, day of gestation, and other environmental factors [8, 27, 28]. Our findings indicate that the BW of fetal pigs undergoes dynamic changes as gestation progresses, suggesting that nutrients are progressively accumulated in fetal pigs. A previous study demonstrated that the BW of fetal pigs increases sharply as gestation progresses, and that 90% of fetal growth occurs during the late stage of gestation [29]. At day 110 of gestation, the BW of HBW fetuses was significantly higher than that of LBW fetuses in the present study, while no significant difference in BW was observed at days 45 and 75 of gestation, suggesting that the within-litter variation of fetal BW becomes more apparent during the late stage of gestation, in accordance with the findings of previous studies [23, 30]. Such findings also indicate that fetal growth retardation occurs principally during the late gestational stage [23, 31].
The nutrient composition of fetal pigs reflects nutritional deposition in the maternal uterus. In the present study, we observed that DM and crude fat concentrations in fetuses increased as gestation progressed, regardless of fetal BW. These findings are consistent with those of previous studies in which DM, CP, and crude fat concentrations increased exponentially in fetal pigs as gestation progressed [15, 29]. In the current study, CP concentration in fetuses with LBW, MBW, and HBW decreased as gestation progressed, possibly due to the use of different body tissues when determining CP. McPherson et al. [29] demonstrated that CP concentration in both fetal carcass and brain decreased as gestation progressed, further suggesting that the rate of CP deposition decreases in the late stage of gestation. At days 75 and 110 of gestation, crude fat concentration in HBW fetuses was significantly higher than that of LBW fetuses, suggesting that distinctions in crude fat concentration occur among fetal pigs of different BWs during mid-gestation and late-gestation, and that HBW fetuses can accumulate more fat than LBW fetuses. Fat concentration is related to energy storage in the body; therefore, our findings suggest that HBW fetuses conserve more energy and are more capable of adapting to the postnatal environment than LBW fetuses.
AAs have extremely different biochemical properties and functions, playing a prominent role not only as building blocks for proteins but also as substrates for the synthesis of a range of physiologically important molecules of immense biological importance [32–34]. Furthermore, AAs are known to exert various effects on body composition, blood flow, metabolic regulation, growth, and development [9]. Several studies have indicated that the concentrations of AAs vary remarkably in fetal fluid during pregnancy [35–37]. An insufficient supply of AAs from the mother to the fetus may result in IUGR [9, 38]. In the present study, Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, and EAA concentrations, as well as EAA/TAA, decreased as gestation progressed, suggesting that the accretion of these AAs in fetal pigs progressively decreases (i.e., the rate of protein deposition decreases as gestation progresses). Suryawan et al. [39] reported that activation of the mammalian target of rapamycin (mTOR), and its effectors including the ribosomal protein S6 kinase (S6K1) and eIF4E-binding protein-1 (4E-BP1), which are positive regulators of protein synthesis, decreases with age in muscle. Thus, the availability of these AAs may become limited, requiring an increase in dietary intake to satisfy the growth and development of fetuses that occur during mid-gestation and late-gestation.
In the present study, we observed increases in Arg, Gly, and Tyr concentrations as gestation progressed, indicating that the demand for these AAs progressively increases throughout gestation. An insufficient supply of Arg is likely to limit the growth and development of fetal pigs during mid-gestation and late-gestation. Dietary supplementation with Arg during these periods may increase the birth weights of piglets and decrease variation in piglet birth weights [40, 41]. Notably, it has been reported that ovine fetuses have a high metabolic demand for Gly during late-gestation [42]. Additional studies have indicated that Tyr concentration increases during mid-gestation and late-gestation, and that Tyr is crucial for proper pigmentation of the skin, hair, and eyes [43]. Taken together, these findings demonstrate that fetuses need more Arg, Gly, and Tyr during mid-gestation and late-gestation to satisfy their developmental needs. Therefore, additional supplementation of these AAs during these periods may improve fetal growth and development.
The LBW fetuses exhibited higher Glu, TAA, and EAA concentrations compared with HBW fetuses at day 75 of gestation, as well as higher Tyr concentration at day 45 of gestation, indicating that the accretion of these AAs in LBW fetuses is greater than that in HBW fetuses during early-gestation or mid-gestation due to the dramatic fetal growth that occurs during late-gestation [23]. However, this result conflicts with previous reports, which indicated that transportation of AAs is decreased in IUGR fetal pigs [44, 45]. This may be because the transportation of AAs does not occur distinctly at day 45 or 75 of gestation.
FAs have remarkable metabolic and regulatory versatility in animals [36]. The fetus demands high levels of FAs, especially PUFA, for optimal growth and development. PUFA must be transported across the placenta due to the limited fetal capacity for its synthesis, especially n-3PUFA and n-6PUFA [46–49]. Fetal accretion of PUFA during the third trimester coincides with a period of substantial growth and continued organ development [50]. In the present study, C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, SFA, and MUFA concentrations increased as gestation progressed, indicating that the synthesis of these FAs in liver increases as gestation advances. This enables the storage of energy for fetal growth and development. Previous studies have indicated that this occurs due to growth of the liver during early-gestation [29]. As gestation progresses, C17:0, C20:4n6, C22:6n3, UFA, PUFA, n-3PUFA, and n-6PUFA concentrations decrease, as do PUFA/SFA and n-3/n-6PUFA, likely due to an inadequate supply of nutrients from the sow, decreasing the synthesis of these FAs. A previous study has also reported that levels of maternal lipids affect the FA composition of fetal tissue [51].
At days 75 and 110 of gestation, LBW fetuses exhibited the lowest C14:0, C16:1, C17:0, C18:2n6c, and MUFA concentrations and the highest C20:4n6, C22:6n3, PUFA, n-3PUFA, and n-3/n-6 PUFA concentrations, suggesting that the deposition of these FAs occurs during mid-gestation and late-gestation. FAs with the highest concentrations (including C20:4n6, C22:6n3, PUFA, n-3PUFA, and n-3/n-6 PUFA) in LBW fetuses may be more important for postnatal growth. Moreover, McNeil et al. [52] reported that the smallest fetuses do not exhibit compromised PUFA status at any stage of gestation.
Conclusions
Maternal body composition changes as gestation progresses. We observed interaction effects between gestation period and BW on DM, CP, crude fat, Tyr, TAA, EAA, C14:0, C16:1, C17:0, C18:0, C18:2n6c, C20:4n6, C22:6n3, MUFA, PUFA, and n-6PUFA concentrations. As gestation progresses, BW increases along with DM and crude fat concentrations, while deposition of CP decreases. The most marked differences occur primarily during mid-gestation and late-gestation. LBW fetuses exhibit decreased amounts of crude fat and several FAs (including C14:0, C16:1, C17:0, and C18:2n6c) during mid-gestation and late-gestation, which may in turn affect the adaptability, growth, and development of the fetus. These findings may provide a theoretical basis for developing nutritional interventions that target fetuses with low birth weight in animals. Additional studies are needed to demonstrate the underlying mechanisms through which these effects occur during gestation.
Acknowledgments
We thank the staff and postgraduate students of Laboratory of Animal Nutritional Physiology and Metabolic Process for collecting samples and technicians from Key Laboratory of Agro-ecological Processes in Subtropical Region for providing technical assistance. We also thank Editage [http://www.editage.cn] for English language editing.
References
- 1. Wu GY, Bazer FW, Cudd TA, Meininger CJ, Spencer TE. Maternal nutrition and fetal development. J Nutr. 2004;134(9):2169–2172. pmid:7408750
- 2. Wang JJ, Chen LX, Li DF, Yin YL, Wang XQ, Li P, et al. Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs. J Nutr. 2008;138(1):60–66. pmid:18156405
- 3. Douglas SL, Edwards SA, Kyriazakis I. Management strategies to improve the performance of low birth weight pigs to weaning and their long-term consequences. J Anim Sci. 2014;92(5):2280–2288. pmid:24671578
- 4. Milligan BN, Dewey CE, de Grau AF. Neonatal-piglet weight variation and its relation to pre-weaning mortality and weight gain on commercial farms. Prev Vet Med. 2002;56(2):119–127. pmid:12450684
- 5. Rehfeldt C, Kuhn G. Consequences of birth weight for postnatal growth performance and carcass quality in pigs as related to myogenesis. J Anim Sci. 2006;84 Suppl:E113–123. pmid:16582082
- 6. Rehfeldt C, Tuchscherer A, Hartung M, Kuhn G. A second look at the influence of birth weight on carcass and meat quality in pigs. Meat Sci. 2008;78(3):170–175. pmid:22062267
- 7. D'Inca R, Che L, Thymann T, Sangild PT, Le Huerou-Luron I. Intrauterine growth restriction reduces intestinal structure and modifies the response to colostrum in preterm and term piglets. Livest Sci. 2010;133(1–3):20–22.
- 8. Wu G, Bazer FW, Wallace JM, Spencer TE. Intrauterine growth retardation: implications for the animal sciences. J Anim Sci. 2006;84(9):2316–2337. pmid:16908634
- 9. Lin G, Wang X, Wu G, Feng C, Zhou H, Li D, et al. Improving amino acid nutrition to prevent intrauterine growth restriction in mammals. Amino Acids. 2014;46(7):1605–1623. pmid:24658999
- 10. Ji Y, Wu Z, Dai Z, Wang X, Li J, Wang B, et al. Fetal and neonatal programming of postnatal growth and feed efficiency in swine. J Anim Sci Biotechnol. 2017;8(1):42. pmid:28484595
- 11. Li FN, Li LL, Yang HS, Yuan XX, Zhang B, Geng MM, et al. Regulation of soy isoflavones on weight gain and fat percentage: evaluation in a Chinese Guangxi minipig model. Animal. 2011;5(12):1903–1908. pmid:224404666
- 12. Yang HS, Fu DZ, Shao H, Kong XF, Wang W, Yang XJ, et al. Impacts of birth weight on plasma, liver and skeletal muscle neutral amino acid profiles and intestinal amino acid transporters in suckling huanjiang mini-piglets. PloS one. 2012;7(12):7. pmid:23236407
- 13. Yang H, Li F, Kong X, Yuan X, Lian G, Geng M, et al. Molecular cloning, tissue distribution and ontogenetic expression of Xiang pig chemerin and its involvement in regulating energy metabolism through Akt and ERK1/2 signaling pathways. Mol Biol Rep. 2012;39(2):1887–1894. pmid:21643960
- 14. Solà-Oriol D, Gasa J. Feeding strategies in pig production: sows and their piglets. Anim Feed Sci & Technol. 2017;233:34–52.
- 15. Wu GY, Ott TL, Knabe DA, Bazer FW. Amino acid composition of the fetal pig. J Nutr. 1999;129(5):1031–1038. pmid:10222396
- 16. Hu CJ, Jiang QY, Zhang T, Yin YL, Li FN, Su JY, et al. Dietary supplementation with arginine and glutamic acid enhances key lipogenic gene expression in growing pigs. J Anim Sci. 2017; 95(12):5507. pmid:29293787
- 17.
AOAC. Official Methods of Analysis. 16th ed Cunniff P, editor Assoc Off Anal Chem Int. 1996.
- 18. Novakofski J, Park S, Bechtel PJ, Mckeith FK. Composition of cooked pork chops—effect of removing subcutaneous fat before cooking. J Food Sci. 1989;54(1):15–17.
- 19. Liu Y, Li F, Kong X, Tan B, Li Y, Duan Y, et al. Signaling pathways related to protein synthesis and amino acid concentration in pig skeletal muscles depend on the dietary protein level, genotype and developmental stages. PloS One. 2015;10(9):e0138277. pmid:26394157
- 20. Kong XF, Yin FG, He QH, Liu HJ, Li TJ, Huang RL, et al. Acanthopanax senticosus extract as a dietary additive enhances the apparent ileal digestibility of amino acids in weaned piglets. Livest Sci. 2009; 123(2–3):261–267.
- 21. Li F, Duan Y, Li Y, Tang Y, Geng M, Oladele OA, et al. Effects of dietary n-6:n-3 PUFA ratio on fatty acid composition, free amino acid profile and gene expression of transporters in finishing pigs. Br J Nutr. 2015;113(5):739–748. pmid:25704496
- 22. Liu Y, Li F, He L, Tan B, Deng J, Kong X, et al. Dietary protein intake affects expression of genes for lipid metabolism in porcine skeletal muscle in a genotype-dependent manner. Br J Nutr. 2015;113(7):1069–1077. pmid:25771944
- 23. Kim SW, Weaver AC, Shen YB, Zhao Y. Improving efficiency of sow productivity: nutrition and health. J Anim Sci Biotechnol. 2013;4(3):187–194. pmid:23885840
- 24. Bidarimath M, Tayade. C. Pregnancy and spontaneous fetal loss: a pig perspective. Mol Reprod Dev. 2017;84(9):856–869. pmid:28661560
- 25. Metges CC, Gors S, Lang IS, Hammon HM, Brussow KP, Weitzel JM, et al. Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs. J Nutr. 2014;144(2):155–163. pmid:24353346
- 26. Hinkle SN, Johns AM, Albert PS, Kim S, Grantz KL. Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth. Eur J Obstet Gynecol Reprod Biol. 2015;190:41–47. pmid:25978857
- 27. Wang J, Feng C, Liu T, Shi M, Wu G, Bazer FW. Physiological alterations associated with intrauterine growth restriction in fetal pigs: Causes and insights for nutritional optimization. Mol Reprod Dev. 2017;84(9):897–904. pmid:28661576
- 28. Rekiel A, Wiecek J, Batorska M, Kulisiewicz J. Effect of sow prolificacy and nutrition on preand postnatal growth of progeny. Ann Anim Sci. 2014;14(1):3–15.
- 29. McPherson RL, Ji F, Wu G, Blanton JR, Kim SW. Growth and compositional changes of fetal tissues in pigs. J Anim Sci. 2004;82(9):2534–2540. pmid:15446468
- 30. Bazer FW, Thatcher WW, Martinatbotte F, Terqui M. Conceptus development in large white and prolific Chinese Meishan pigs. J Reprod Fertil. 1988;84(1):37–42. pmid:3184056
- 31. Yuan TL, Zhu YH, Shi M, Li TT, Li N, Wu GY, et al. Within-litter variation in birth weight: impact of nutritional status in the sow. J Zhejiang Univ Sci B. 2015;16(6):417–435. pmid:26055904
- 32. Wu G, Bazer FW, Dai Z, Li D, Wang J, Wu Z. Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci. 2014;2:387–417. pmid:25384149
- 33. Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009;37(1):1–17. pmid:19301095
- 34. Brosnan JT. Amino Acids, Then and now—a reflection on sir Hans Krebs' contribution to nitrogen metabolism. Iubmb Life. 2001;52(6):265–270. pmid:11895074
- 35. Kwon H, Spencer TE, Bazer FW, Wu G. Developmental changes of amino acids in ovine fetal fluids. Biol Reprod. 2003;68(5):1813–1820. pmid:12606398
- 36. Kim SW, Mateo DR, Yin YL, Wu G. Functional amino acids and fatty acids for enhancing production performance of sows and piglets. Asian-Austral J Anim Sci. 2007;20(2):295–396.
- 37. Bazer FW, Song G, Kim J, Dunlap KA, Satterfield MC, Johnson GA, et al. Uterine biology in pigs and sheep. J Anim Sci Biotechnol. 2012;3(1):23. pmid:22958877
- 38. Wu G. Functional amino acids in growth, reproduction, and health. Adv Nutr. 2010;1(1):31. pmid:22043449
- 39. Suryawan A, Escobar J, Frank JW, Nguyen HV, Davis TA. Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs. Am J Physiol. 2006;291(4):849–859. pmid:16757550
- 40. Wu X, Yin YL, Liu YQ, Liu XD, Liu ZQ, Li TJ, et al. Effect of dietary arginine and N-carbamoylglutamate supplementation on reproduction and gene expression of eNOS, VEGFA and PlGF1 in placenta in late pregnancy of sows. Anim Reprod Sci. 2012;132(3–4):187–192. pmid:22682770
- 41. Quesnel H, Quiniou N, Roy H, Lottin A, Boulot S, Gondret F. Supplying dextrose before insemination and L-arginine during the last third of pregnancy in sow diets: effects on within-litter variation of piglet birth weight. J Anim Sci. 2014;92(4):1445–1450. pmid:24492569
- 42. Bloomfield FH, van Zijl PL, Bauer MK, Harding JE. Effects of intrauterine growth restriction and intraamniotic insulin-like growth factor-I treatment on blood and amniotic fluid concentrations and on fetal gut uptake of amino acids in late-gestation ovine fetuses. J Pediatr Gastroenterol Nutr. 2002;35(3):287–297. pmid:12352515
- 43. Sturm R. Molecular genetics of human pigmentation diversity. Hum Mol Genet. 2009;18(R1):R9–17. pmid:19297406
- 44. Jansson T, Scholtbach V, Powell TL. Placental transport of leucine and lysine is reduced in intrauterine growth restriction. Pediatr Res. 1998;44(4):532–537. pmid:9773842
- 45. Avagliano L, Garo C, Marconi AM. Placental amino acids transport in intrauterine growth restriction. J pregnancy. 2012;2012:1–6. pmid:22997583
- 46. Hanebutt F, Demmelmair H, Schiessl B, Larqué E, Koletzko B. Long-chain polyunsaturated fatty acid (LC-PUFA) transfer across the placenta. Clin Nutr. 2008;27(5):685–693. pmid:18639956
- 47. Cetin I, Koletzko B. Long-chain omega-3 fatty acid supply in pregnancy and lactation. Curr Opin Clin Nutr Metab Care. 2008;11(3):297–302. pmid:18403927
- 48. Helland I, Saugstad O, Saarem K, Van Houwelingen A, Nylander G, Drevon C. Supplementation of n-3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants. J Matern Fetal Neonatal Med. 2006;19(7):397–406. pmid:16923694
- 49. Cetin I, Alvino G, Radaelli T, Pardi G. Fetal nutrition: a review. Acta Paediatr Suppl. 2005;94(449):7–13. pmid:16214758
- 50. Robinson DT, Martin CR. Fatty acid requirements for the preterm infant. Semin Fetal Neonatal Med. 2017;22(1):8–14. pmid:27599697
- 51. Perez Rigau A, Lindemann M, Kornegay E, Harper A, Watkins B. Role of dietary lipids on fetal tissue fatty acid composition and fetal survival in swine at 42 days of gestation. J Anim Sci. 1995;73(5):1372–1380. pmid:7665366
- 52. McNeil CJ, Finch AM, Page KR, Clarke SD, Ashworth CJ, McArdle HJ. The effect of fetal pig size and stage of gestation on tissue fatty acid metabolism and profile. Reproduction. 2005;129(6):757–763. pmid:15923391