FN 490: Embryonic and Fetal Growth and Development: Nutritional Influences

I.	Embryonic and fetal growth and development consists of a series 
	of coordinated events which need to occur in proper time and space.
	
	1.	Growth

		A.	An increase in body weight until mature size 
			is reached
		B.	Increase in cell size and cell numbers 
			with protein deposition
		C.	Usually an increase in structural tissues 
			and organs

	2.	Development

		A.	Directive coordination of all diverse processes 
			until maturity is reached
			a.	Growth
			b.	Cellular Differentiation
			c.	Changes in body shape and form

II.	Stages of Embryo and Fetal Development

	1.	Three phases of embryo and fetal development

		A.	Blastogenesis (d 0-4)
			a.	Zygote to Blastocyst (Blastula)
			b.	Cell division without growth

		B.	Embryonic Period (d 5-60)
			a.	Blastocyst to Fetus
			b.	Period of Differentiation

		C.	Fetal Stage (~d 60 to birth)
			a.	Period of Growth
	2.	Blastogenesis

		A.	Zygote

			a.	One cell fertilized egg
			b.	Large Cell–Low Nuclear:Cytoplasm Ratio

		B.	Cleavage Stage (d 1-4)

			a.	Cell division without and increase 
				in cell mass
			b.	Increase Nuclear:Cytoplasm Ratio
			c.	Negative Growth
			d.	Result in Morula (latin for mulberry)
				i. 	~32 cell stage
				ii. 	Compaction
					--Polarization




	3.	Embryonic Stage

		A.	Morula to Blastocyst Transition

			a.	Outer cells becomes early placenta
				i. 	Cells flatten and are joined 
					by tight junction		
				ii. 	Trophoblasts or trophectoderm
			b.	Inner cells become early embryo
				i.	Gap juctions form between cells
			c.	Fluid filled cavity forms called 
				a blastocoel.			

		B.	Blastocyst hatches from zona pelucida (shell)
		C.	Implantation

			a.	Blastocyst penetrates uterine mucosa 
				into submucosa (d 6-7)
			b.	Pockets in uterus called lacunae
			c.	Lacunae fill with maternal blood 
				(d 12)
			d.	Trophoblasts send out villi which become 
				anchored to maternal tissue
			e.	Provide for exchange of nutrients 
				and growth factors between mother and embryo

		D.	Maternal recognition of pregnancy 
			(d 14-16)

			a.	Prevents luteolysis
			b.	Corpus luteum needed to maintain pregnancy
				i.	Progesterone quites uterus 
					and causes uterine secretions 
					needed for pregnancy.
		E.	Gastrulation

			a.	Inner cell mass differentiates 
				into Germ Layers
				i.	Ectoderm
				ii.	Mesoderm
				iii.	Endoderm

		F.	Organogenesis
		
			a.	Germ layers differentiate

				i.	Ectoderm
					--Brain, nervous system, hair, 
						and skin
					--Neural tube a primary target 
						of malnutrition
				ii. 	Mesoderm
					--Muscles, Bones, Cardiovascular,
						Reproductive, and Excretory 
						Systems
					--Also a major target of malnutrition 
						and toxins.
				iii. 	Endoderm
					--Digestive and respiratory systems, 
						some glandular organs.

			b.	Mechanisms of growth and differentiation

				i. 	Hyperplasia:  Increased mitosis
				ii. 	Hypertrophy:  Increase cell size
				iii.    Apoptosis:  Programmed cell death
				iv. 	Cell migration

		G.	Placentation

			a.	Fetal membranes develop from trophectoderm
				or trophoblasts
			b.	Fetal Membranes
				i. 	Yolk sac
					--Waste Products
				ii. 	Amnion
					--Fetal Protection (Physical)
				iii. 	Allantois
					--Fetal Blood Supply
				iv. 	Chorion
					--Outer layer
					--Maternal link
			c.	Placenta is an important factor 
				for normal embryo and fetal development

	4.	Fetal Stage

		A. 	When species is recognizable by body structure 
			and shape

		B. 	Growth Rate
			a. 	Relative growth
				--fastest early gestation
			b.    Absolute growth
				 --Maximum late in gestation

		C. 	Factors affecting fetal growth

			a.	Genetics
			
				i. 	Influenced by maternal and paternal genotype
				ii.  	Sex

			b.	Environment
			
				i. 	Mother
					--Nutrition, Health, Size, Parity
				ii.     	Placenta
					--Blood Flow, Size
				iii. 	Multiple birth

			c.  	Hormone

				i.	Sex Steroid Hormones
				ii. 	Thyroid hormone
				iii. 	Insulin
				iv.  	Placental Lactogen	
				v. 	Somatotropin
				vi. 	Glucocorticoids
				vii.  Growth Factors


III.  	Nutritional Aspects of Embryonic and Fetal Development

	1.	Maternal Nutrition

		A. 	Reproduction does not occur properly without 
			proper nutrition

		B.	Without an adequate supply of food 
			and the nutrients it contains, 
			an organism cannot grow and develop normally, 
			and possibly die

		C.	Effects of Malnutrition

			a.	Low birth weight
			b.	Reduced placenta size (number and size)
			c.	Reduced brain cell and head size
			d.	Proportional reductions in the size 
				of other organs
			e.	Alterations in normal cell constituents 
				and biochemical processes

		D.	Consequence depends on timing, severity, 
			and duration of malnutrition.

			a.	Results can be reversible if hypertrophy 
				is affected
			b.	Results can be irreversible if hyperplasia 
				is affected

	2.	Effects of Alcohol, Caffeine, Artificial Sweetners, 
		and Smoking

		A.	Chronic Alcohol (Fetal Alcohol Syndrome)

			a.	Anomolies of eyes, nose, heart, CNS
			b.	Low birth weight, small head circumferance, 
				mental retardation
			c.	Infant irritablity and hyperactivity
			d.	Moderate consumption can also cause 
				detriments
				i.	Dependent on maternal nutrition 
					and health
		B.	Caffeine
			a.	High levels can cause limb defects
			b.	Alter blood flow through uterus 
				and placenta
			c.	Stimulate cAMP pathways in cells

		C.	Artificial Sweetners
			a.	No clear results
			b.	Saccharin may be carcinogenic 
				in high levels.
			c.	Used in moderation probably OK.

		D.	Smoking
			a.	Low birth weight and length

	3.	Role of Placenta

		A.	Placenta size positively correlated 
			to birth weight and inversely correlated 
			with embryonic/fetal abnormalities

		B.	Placental Functions
			a. 	Endocrine
			b.	Respiration
			c.	Digestion
			d.	Excretion
			e.	Protection
				i. 	Immunological
				ii. 	Physical
		C.	Mechanisms of Placental Nutrient Transfer

			a. 	Passive Diffusion
				i. 	Oxygen, Carbon Dioxide, Fatty Acids
					Steroids, Nucleosides, Electrolytes,
					Fat-Soluble Vitamins
			b. 	Facilitated Diffusion
				i. 	Glucose
			c. 	Active Transport
				i. 	Amino Acids
			d.	Solvent Drag
				i.	Electrolytes

	4.	Role of Hormones

		A.	The pregnant women secretes more 
			than 30 different hormones during gestation

		B.	Progesterone

			a.	Source
				i. 	Ovary--Early Pregnancy
				ii. 	Placenta--Later Pregnancy
			b.	High throughout pregnancy, drops 
				just before birth
			c.	Effects
				i. 	Reduce gastric motility; 
					favors maternal fat deposition;
					increases sodium excretion; 
					reduces alveolar and arterial Pco2; 
					interferes with folic acid metabolism
			d.	Folic acid should be supplemented during 
				pregnancy to reduce neural tube defects.

		C.	Estrogen
	
			a.	Source
				i. 	Primarily Placenta
			b.	Low most of pregnancy, increases rapidly 
				near term
			c.	Effects
				i. 	Reduces serum proteins; 
					increases hydroscopic properties 
					of connective tissue; 
					affects thyroid function; 
					interferes with folic acid metabolism; 
					may interfere with insulin action.

		D.	Thyroxine

			a.	Effects:  Regulates rate of cellular 
						oxidation (metabolism)
			b.	Regulation:
				i. 	Thyroid stimulating hormone (TSH)
				ii. 	Estrogen
					--Counteracts TSH overstimulation

		E.	Insulin

			a.	Effects:
	
				i. 	Reduces blood glucose levels 
					to promote energy production 
					and synthesis of fat
				ii. 	Also needed in the initiation 
					of lactation

			b.	Insulin becomes less efficient as pregnancy 
				goes on.

				i. 	Insulin can't keep up 
					with high glucose load
					--Occurs Late 2nd and 3rd trimester
				ii. 	Other hormones of pregnancy also 
					antagonize insulin effects.
				iii. 	If severe, gestation diabetes 
					can occur

			c.	Gestational Diabetes

				i. 	Risk Factors
					--Obesity; Family history 
						of diabetes; Previous 
						history of large infant, 
						still birth, or child with 
						birth defect; Too much 
						amniotic fluid; age of 
						mother.

				ii.  	Treatment
					--Special diet; Exercise; Glucose 
						Monitoring; Insulin
					--Dependent on severity and 
						other circumstances

				iii. 	Complications for Baby
					--Macrosomia: Larger than normal 
						body due to extra fat 
						deposits.
					--Hypoglycemia: High baby insulin 
						stays high after birth.
					
		F.	Placental Lactogen; Growth Hormone; and Cortisol

			a.	All antagonize insulin by increasing blood 
				glucose
				i. 	 Can complicate diabetes

			b.	Placental Lactogen
				i. 	Important in immunosuppresion 
					and may breakdown insulin 
					in placenta

			c.	Growth hormone
				i. 	Stimulate growth of long bones 
					and promote nitrogen retention
				ii.  	IGFs often mediate action

			d. 	Cortisol
				i. 	Involved in parturition 
					and initiation of lactation
		G. 	Growth Factors

			a.	IGFs--Bone growth, Fat cell proliferation, 
					etc.
			b.	FGF--Limb formation, myoblast proliferation, 
					etc.
			c.	NGF--Nerve Growth, etc.
			d.	EGF--Epithelial tissue growth, etc.
			e.	MIF--Reproductive system differentiation

	5.	Recommended Daily Allowance during Pregnancy

		A.	Everything needs to be increased to keep up 
			with growth and development of fetus.
		B.	Multivitamin supplements recommended
			a.	Folic Acid is biggest concern.