FETAL GROWTH AND DEVELOPMENT Erika Edwards ANS 536 Overview • Growth Terminology • What affects growth • Hormones • Proteins • Body Condition Scoring • Underfeeding Dams • Overfeeding Dams • Implications of Under/Overfeeding • Hormonal Therapy Growth • Conception to blastocyst stage= hyperplasia • Mitotic division • Proliferation and cleavage into non-specific cells • Generally not influenced by maternal or environmental changes • Blastocyst-birth= hypertrophy • Cells become specific organs • Can be influenced by mother and environment Tissue Accretion Cell growth= tissue gain Formation of organ systems occurs through the building of tissue Cell Cell Cell Cell Cell Cell Cell Cell What affects growth? • Genetics • Potential- genetic code • Transcription- phenotype • Physical environment • Uterine Capacity- restrictor • Nutrient availability- metabolism • Interaction between the two • Hormones • Growth factors • Transcription factors PROTEIN Hormones and Proteins affecting Fetal Growth • Progesterone • Estrogen • Growth Hormone • Insulin-like Growth Factors (IGF-1 and IGF-2) • Glucocorticoids • Nitric Oxide • Arginine Progesterone • “Hormone of pregnancy” • Levels increase around conception • Remain high through pregnancy • Secreted from the CL then the placenta starting at week 8 • Function • Keep uterus from contracting • Promote secretion of histotroph • Exogenous treatment can enhance fetal growth Research with Progesterone • Cows treated day 1-4 of pregnancy have higher fetal growth • Treated cows=37.3 mm embryo vs. Non-treated cow= 3.8 mm embryo • Fetal growth is highest when given on day 1-3 of pregnancy in sheep • Growth during midgestation • Can be administered on day 1-3 or day 3-6 though Estrogen • “Excitatory hormone” • Secreted from ovaries • Function • Stimulate other hormones to cause ovulation • Estrogen: Progesterone ratio is important • Closely-linked • Preterm birth connected to high estrogen: progesterone ratio • Levels are low during pregnancy Growth Factor • Synthesized, stored, and secreted from AP gland • Function • Stimulates overall growth, cell reproduction and cell regeneration due to stimulation placental vascularization • Has no direct affect until after birth • Part of all stages of pregnancy • Mother influences until end of 1st trimester • Fetus takes over at this time • Higher in male fetuses than female fetuses • Due to sexual differentiation of the hypothalamus • Treatment in blastocysts will increase implantation once in the uterus • Maternal growth hormone accounts for up to 40% of varying birth weight Research with GH • Sheep • Exogenous treatment has no effect • Pigs • Exogenous treatment can increase fetal body weight by 20% • If given during midgestation, birth length and muscle will increase while back fat decreases Insulin-like Growth Factors • Proteins that have similar molecular structure to insulin • Secreted by the liver mostly • Function of IGF-2 • Early development and function in various organs • Function of IGF-1 • Promote cell growth • Prevent cell death • Increase placental transfer capacity • Circulating in fetus as early as 1st trimester • Higher in female fetuses than male fetuses • Levels highest in early gestation • Deficiency can reduce fetal body weight by as much as 60% Glucocorticoids • Function • Lung maturation • Surfactant production • Brain development • Cortisol (a glucocorticoid) • Levels rise at end of pregnancy to induce final maturation of organs • Preterm babies can be injected with dexamethasone to assist with maturation • 161 grams heavier is administered this drug http://ansci.illinois.edu/static/ansc438/Motherneonate/hormonechanges.html Nitric Oxide • Function • Regulator of blood flow across placenta • Affected by insulin resistance • Insulin is supposed to increase muscle growth and inhibit muscle degradation • Compromises placental delivery of nutrients and oxygen • Elevated levels inhibit adipocyte growth Arginine • Function • Regulate cell proliferation and differentiation • Facilitate growth of muscle fibers and adipocytes in fetus • Reduced levels in fetuses underweight BSC in Dairy Cattle http://www.intechopen.com/books/artificial-insemination-in-farm-animals/particularities-of-bovineartificial-insemination Maternal Undernutrition and Fetal Growth • Reduces blood flow across placenta and stunts growth • Sheep study- reduced birth weight by 25% • Hormone Imbalance=Intrauterine growth restriction • Increase in circulating progesterone, but endometrial concentrations are reduced • Increased fetal growth hormone with immediate undernutrition • IGF-1 is decreased, so creates a disruption in GH-IGF-1 axis • Decrease in fetal growth hormone when chronically undernourished Maternal Undernutrition and Fetal Growth • IGF-1 mRNA transcripts in liver reduced • Continues even if dam is returned to normal nutrient intake • Glucocorticoids increase Maternal Overnutrition and Fetal Growth Wu, G., Bazer, F. W., Cudd, T. A., Meininger, C. J., & Spencer, T. E. (2004). Maternal Nutrition and Fetal Development, (13), 2169–2172. Implications of Under/Overfeeding • Low birth weight= high morbidity and morality • Weak • Not fully developed or developed correctly • Never reach full potential • Reduced efficiency of nutrient utilization • Many health issues • Metabolic • Endocrine • Cardiovascular • Small carcass • Issues with meat quality Hormonal Therapy • Progesterone • Help with fetal growth in overfed livestock • Growth Hormone • Treat in late pregnancy • Increase in arginine availability • Increase in fetal weight • Large increase in adipose tissue Questions? Sources Ferrell, Calvin L., "Factors Influencing Fetal Growth and Birth Weight in Cattle" (1993). Roman L. Hruska U.S. Meat Animal Research Center. Paper 132. Field, M.E., et al. Duration of maternal undernutrition differentially alters fetal growth and hormone concentrations. Domestic Animal Endocrinology. 2015; 51:1-7. Garrett, JE, et al. Evidence for maternal regulation of early conceptus growth and development in beef cattle. Journal of Reproductive Fertility. 1988; 84(2):437-446. Gilbert, SF. Developmental Biology. 6th editon. Sinauer Associates. 2000. Healthy Women. “Progesterone Overview.” 2015. Web. Kleeman DO. Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy. Journal of Reproductive Fertility. 1994; 102(2):411-417. Laron, Z. Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. The Lancet. 1992; 333(8804): 1258-1261. Laron, Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Journal of Clinical Pathology. 2001; 54: 311-316. Mazor, Moshe, et al. Human preterm birth is associated with systemic and local changes in progesterone/17-betaestradiol ratios. American Journal of Obstetrics and Gynecology. 1994; 171(1);231-236. McIntyre, HD, et al. Placental growth hormone (GH), GH-binging protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth. Journal of Clinical Endocrinology Metabolism. 2000; 85(3):1131-1150. Mucci, Lorelei, et al. Pregnancy estriol, estradiol, progesterone, and prolactin in relation to birth weight and other birth size variables (United States). Cancer Causes and Control. 2003; 14(4):311-318. Sources Cont’d. Murphy, VE, et al. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocrine Review. 2006; 27(2): 141-169. Pansky, Ben. Chapter 25: Germ Layers and Their Derivatives. Medical Embryology. Rhind, S.M. Effects of maternal nutrition on fetal and neonatal reproductive development and function. Animal Reproduction Science. 2004; 82-82: 169-181. Waters, M.J. and Kaye P.L. The role of growth hormone in fetal development. Growth Hormone & IGF Research. 2002; 12(3): 7-146. Woodall, S.M. et al. Consequences of maternal undernutrition for fetal and postnatal hepatic insulin-like growth factor-I, growth hormone receptor and growth hormone binding protein gene regulation in the rat. Journal of Molecular Endocrinology. 1998; 20:313-326. Wu, G., et al. Board-Invited Review: Intrauterine growth retardation: Implications for the animal sciences. Journal of Animal Science. 2006; 82: 2316-2337.