DAY	EVENT	WHERE
0	Ovulation	Ovarian Follicle
1 (end)	Fertilization	Ampullary-Isthmic Junction
3	Morula	Fallopian Tube
4	Early Blastocyst	into Uterus
5	Late Blastocyst zona pellucida degenerates	Uterine Glands secrete protease + uteroglobin
6	sticks to epithelium	Endometrium
7	Implantation begins	Endometrium
10	Implantation complete

	C. Implantation


		1. Inner Cell Mass -gives rise to ® Embryonic Disc

			a. Day 8 in humans 

	
			b. now called an Embryo

				i. 2nd through 8th week

					(1) 9th week ® called a Fetus


		2. Syncitium - cells having communicating cytoplasm
		
			a. syncytiotrophoblast aggressively burrows into endometrium
			
			b. only embryonic tissue in direct contact with maternal tissue
			
				i. becomes outer layer of placenta
			
		
		3. Deciduoma

			a. implantation becomes so complete that cells of the
			    endometrium completely cover the embryo


		4. Formation of the Amnion and other Extra-Embryonic Membranes

			a. extra-embryonic membranes 		

				i. Amnion


				ii. Yolk Sac			

					(1) germ cells


				iii. Allantois					 


				iv. Chorion 						

					(1) from cytotrophoblast


			b. Sinusoids develop 

				i. pools of blood rather than vessels

					(1) enzyme secreted by syncytiotrophoblast 
					    lyses uterine blood vessels

					(2)  Day 9 in humans

			c. implantation complete on Day 10 in humans

			d. Chorionic Villi formed 

				i. outgrowths of chorion into sinusoids

					(1) Day 11 in humans


				ii. Hemo-Choriol Placenta in humans

					(1) fetus' chorion bathed directly
					   in maternal blood

			e. Day 14 = Missed Menstrual Peroid
			

		5. Amnion

			a. Filled with fluid

				i. 5-10 ml at 8 wks

				ii. 1000-1500 ml 38 wks

				iii. 500-1000 ml term

			b. Provides buffer against shock

			c. fetus swallows fluid


		6. Yolk Sac

			a. Produces Primordial Germ Cells

			b. Hemopoietic Organ


		7. Allantois

			a. Contributes Blood Vessels to Placenta

				i. becomes Umbilical Circulation

					(1) Vein goes to the Heart
					   (usually deoxygenated)

					(2) Arteries go away from the heart
					 (usually oxygenated)

	D. Placenta

		1. Disc shaped structure, a combination of fetal and
		   maternal tissue = discoid placenta


		2. Hemochorial Placenta

			a. maternal blood directly bathes the chorionic villi


			b. maternal blood never mixes with fetal blood


				i. membranes of the chorionic villi and capillaries
				   keep them separate


		3. Chorio-Allantoic Placenta

			a. Villi tissue from chorion


			b. vessels from allantois


		4. Delivery and Excretion


			a. delivers O2,	 removes CO2


			b. delivers amino acids, 	removes urea


			c. delivers sugars and fats


			d. delivers hormones


				i. T3 to fetus (early)


				i. Estrogen (estriol = E3) to mother


		5. Endocrine Organ


	E. Endocrinology of Pregnancy


		1. Chorionic Gonadotropin (for humans: hCG)

			a. produced by cells of the chorion or trophoblast


				i. chorion develops from the trophoblast


			b. cytotrophoblast produces hCG
			   very early in embryonic life


				i. most early pregnancy tests confirm pregnancy
				   by binding to hCG with a specific antibody and
				   then to a color producing molecule


				ii. hCG is produced even before implantation


			c. hCG prolongs the life of the corpus luteum
			   and the production of P


			d. hCG stimulates placental production of E and P
			
			
			e. hCG protects ovarian follicles ® 
			   without stimulating growth or steroidogenesis


		2. Progesterone


			a. Maternal blood supplies cholesterol


			b. Placenta converts cholesterol to Progesterone


				i. takes over following luteolysis


				ii. produces enough to support pregnancy
				      by 5-6 wks in humans


			c. P is necessary for endometrial support and secretion


				i. \ P is necessary for support of pregnancy


					(1) pro = support ... gest = gestation = pregnancy


			d. exerts negative feedback on LH and FSH

				i. ovarian follicles don't grow
				
				
				ii. no stimulation for ovarian steroid production 


			e. increases fat deposition

				i. stimulating appetite

				ii. diverting energy stores from sugar to fat
				

		3. Feto-Placental Unit  -  Estrogens

			a. Progesterone from Placenta to fetal adrenal gland


				i. through umbilical and fetal vasculature


			b. outer layers = fetal adrenal zone converts P to DHEA


			c. DHEA circulates to fetal liver ® converted to
			    16a-OH-DHEA sulfate


			d. converted to Estriol in the Placenta


				i. E3 is the primary estrogen during pregnancy


			e. fetus and placenta cooperate to produce
			   maternal estrogens


		4. Chorionic Somatomammotropin = Placental Lactogen

			a. hCS = hPL like PRL help prime mammary glands
			    for later milk secretion


				i. with estrogens and progesterone


			b. and has effects similar to GH


			c. placenta also secretes PRL
			

		5. Relaxin

			a. secreted by the corpus luteum and then the placenta


			b. levels rise late in pregnancy


			c. Loosens connective tissue


				i. widens pubic symphysis so head can pass through


			d. inhibits spontaneous uterine contractions


			e. promotes cervical effacement

				i. flattening, spreading, dilation of cervical os


		6. Placenta also secretes

			a. Chorionic GnRH

			b. Chorionic CRH and Corticotropin (ACTH)

			c. Chorionic Thyrotropin (TSH)

			d. Chorionic Endorphins


		7. Change in hormone levels during pregnancy


	F. Fetal Development

		1. Growth

			a. slow to week 20, maximum weeks 30-36, then slower


			b. stimulated by hCS, maternal Growth Factors (e.g. IGFs)
			    and fetal thyroid hormones (later)

				i. not stimulated by Growth Hormone (GH)

					(1) not effective prenatally

						(a) postnatally GH works 
						    by inducing IGFs

			c. Maternal Nutrition and Health

				i. diet, calcium, vitamins

					(1) fetus usually supplied first
					
						(a) an undernourished fetus has an 
						  Ý chance of obesity as an adult

				ii. smoking

					(1) reduced size, slowed development

				iii. alcohol

					(1) reduced neural development

				iv. any drug should be verified by a physician


		2. The Nervous System

			a. thyroid hormones necessary
			
			b. 5-HT necessary (from neural tissue)

			c. masculinization of the brain by T ® E2

			d. many drugs affect neural development
			   due to their lipid solubility

				i. even painkilling drugs given during labor

			e. neural induction  of other tissues

				i. nervous tissue (neural crest) helps 
				   direct development of other tissues

					(1) eg. endocrine system, musculature


			f. motor nerves effective by 14 weeks in humans

				i. fetal movements help develop motor nervous system


		3. Immune System

			a. the fetus has many antigens

				i. the fetus is seen as a foreign 
				   object by the mother

					(1) important for the success of pregnancy

					
			b. Immunological Filter

				i. syncytiotrophoblast lacks antigen activity

				ii. P and hCG act locally as immunosuppressants 

				iii. some maternal antibodies cross the placenta

					(1) IgG

					(2) confers some passive immunity
					   (including postnatally)

					(3) also delivered in maternal milk

					(4) stimulates development of 
						fetal immune system

					(5) Rh

						(a) mixing fetal and maternal blood 
						    during birth results in Rh antibody
							expression 

						(b) subsequent pregnancies antibodies 
						    destroy fetal red blood cells


		4. Respiratory System


			a. fetus makes respiratory movements at least 1-4 h / day

				i. motor nerves necessary


			b. primitive air sacs develop by week 20

				i. vascularized by 28 wks


			c. development enhanced by cortisol from the adrenal


			d. surfactant

				i. as lung increases in size it is necessary for
				    expansion of lungs without collapse


		5. Endocrine System


			a. hCG produced early but will not remain
			    part of the fetal endocrine system


			b. Thyroid gland

				i. T3/T4 necessary for development

					(1) thyroid secretory by week 20


				ii. fetal levels may exceed maternal


				iii. oviparous animals may include T3/T4
				     in the yolk of eggs


			c. Pituitary

				i. functional throughout most of fetal life

				ii. TSH to stimulate T3/T4 

				iii. LH, FSH, and ACTH


			d. Adrenal Gland (Cortex)


				i. begins by aiding production of estriol and is
				   converted to production of cortisol (F) as
				   development progresses
				   
				   
				   	(1) both E3 and F are regulated
					    by CRH during pregnancy


				ii. cortisol necessary for 


					(1) lung maturation


					(2) liver enzymes


					(3) pancreas insulin cell maturation


					(4) synthesis of adrenaline


					(5) hemoglobin formation


					(6) parturition


						(a) stimulation of placental and 
						    hypothalamic CRH


						(b) postpartum stress response