Weirong Gu Obsterics & Gynecology Hospital of Fudan university Physiology of Pregnancy

Pregnancy The condition of being with baby, is the process of embryo and fetus growing and developing in the uterus From the fertilization to the expelling of the fetus with placenta and membranes last 40 weeks from the first day of the last menstrual period

Contents Fertilization, development, transport and implantation of fertilized ovum Formation and function of fetal attachment Maternal changes during pregnancy

Concepts Sperm capacitation Fertilization Acrosome reaction Zona reaction

Sperm capacitation Spermatozoons contact with endometrium The α-/β- amylase remove the decapacitation factor on spermatozoons’ acrosomal enzyme The spermatozoons with the ability of fertilization(capacitation)in uterus and fallopian tubes

Acrosome reaction Acrosome ruptures, acrosomal enzymes release and lysis the radiate corona and zone pellucida The spermatozoon can penetrate and fuse with oocyte

Zona reaction The cortical particle of cytoplasm release lysosomal enzyme Zona structure changed and sperm receptor degenerated to prevent other sperm into the zona ——single oocyte fertilization

Fertilization The course of combination of the oocyte and sperm Time : 12h after ovulation Place : usually in ampulla of the oviduct (fallopian tube)

Development and transport of the zygote begin to move towards cavity after 30 hours form blastomere by cleavage the volume doesn’t enlarge the morula (early blast) is fomulated early blastomere fomulated enter uterine cavity zona disappear blastocyst enlarge late blastocyst implants in endometrium

Implantation Late blastosphere implanted in endometrium  Apposition : at upper part of paries posterior uterus  Adhesion: with innner cell mass  Penetration: syncytiotrophoblast secrete protein resolvase to lysis endometrium cells, stroma,and vessels

The necessary condition of implantation Disapearing of the zona pellucid Formation of syncytiotrophoblast Synchronizing development of blastocyst and endometrium Adequate progesterone

Changes of endomertium after implantation The endometrium changes into dicedua  Basal decidua: contact with blastomere  Capsular decidua: cover the blastomere  Ture decidua: covers cavity, fuse with capsular decidua at 14-16w Ture decidua Basal decidua capsular decidua

Embryo and fetal development Embryo the first 8 weeks from pregancy organs differentiated Fetus after 9 weeks from pregnancy organs matured

4 gestational weeks 8 gestational weeks balstoderm and body stalk recognized human shape formed ， early cardiac tube pulse visible on ultrasound

12 Gestational Weeks  Uterus palpable above the symphysis pubis  Fetal crown-rump length ： 6 to 7 cm  Fingers and toes differentiated  Skin and nails developed  The external genitalia beginning to show definitive signs of male or female gender  Begin to make spontaneous movements

16 Gestational Weeks  Fetal crown-rump length: 12 cm  Weight : 110 g  Gender can be determined by 14 weeks

20 Gestational Weeks  Weight: more than 300 g, and increase in a linear manner  Movement: about every minute and is active 10 to 30 percent of the time  Skin : less transparent, a downy lanugo covers entire body, some scalp hair has developed.

24 Gestational Weeks  Weight: about 630 g  The skin is characteristically wrinkled, and fat deposition begins  The head is still comparatively large, and eyebrows and eyelashes are usually recognizable  The canalicular period of lung development, during which the bronchi and bronchioles enlarge and alveolar ducts develop, is nearly completed  A fetus born at this time will attempt to breathe, but many will die because the terminal sacs, required for gas exchange, have not yet formed

28 Gestational Weeks  The crown-rump length is approximately 25 cm, and the fetus weighs about 1100 g  The thin skin is red and covered with vernix caseosa  The pupillary membrane has just disappeared from the eyes  The otherwise normal neonate born at this age has a 90-percent chance of survival without physical or neurological impairment

32 Gestational Weeks  The fetus has attained a crown-rump length of about 28 cm and a weight of approximately 1800 g  The skin surface is still red and wrinkled

36 Gestational Weeks  The average crown-rump length of the fetus is about 32 cm, and the weight is approximately 2500 g  Because of the deposition of subcutaneous fat, the body has become more rotund, and the previous wrinkled appearance of the face has been lost

40 Gestational Weeks  This is considered term from the onset of the last menstrual period  The fetus is now fully developed  The average crown-rump length is about 36 cm, and the weight is approximately 3400 g

Physiology of fetus Circulation  Fetus connects with mother by placenta and umbilical cord  umbilical cord 1 umbilical vein (full of oxygen) 2 umbilical arteries (lack of oxygen)

Anatomy characters between aorta and pulmonary artery Foramen ovale between interatrial septum between superior and inferior vena cava Mixed arterial and venous blood Ductus arteriosus Foramen ovale Ductus venosus

Hematology Erythropoiesis  From yolk sac: 3 weeks  From liver: 10 weeks  From bone marrow and spleen: term (90%) EPO production: engender quantity at 32 nd week, so fetal red cell numbers increase Fetal blood volume:125ml/kg of the fetus at term

Fetal hemoglobin  Fetal hemoglobin: early pregnancy  Adult hemoglobin: 32 nd week  Term : fetal type Hb 25% White cells  Leukocytes: emerge at 8 week in fetal circulation  Lymphocytes (antibody production): 12 week thymus and spleen

Fetal respiratory system  The timetable of lung maturation and identification of biochemical indices of functional fetal lung maturity are important to the obstetrician  A sufficient amount of surface-active materials in the amniotic fluid is evidence of fetal lung maturity  Surfactant: produced by type Ⅱ cells of the lung alveoli; active component is a specific lecithin or phosphatidyl glycerol

Gastrointestinal tract  Swallowing begins at weeks  Gastrointestinal function is established at 16weeks Liver  Hepatic enzyme is lack during fetal period, a very limite capacity for converting free bilirubin to conjugating bilirubin

Urinary system  The fetal kidneys start producing urine at 12 weeks’ gestation  7-14ml/d by 18 weeks  27ml/hr or 650ml/d at term Genital system  Genital organ is developed from 9 weeks of pregnancy(male), weeks(female)

Attachment of fetus Placenta Fetal membranes Umbilical cord Amniotic fluid

Placenta An exchange organ between mater and fetus  Organization Amniotic membrane Chorion frondosum Basal decidua

Chorion frondosum days after ovulation, villi fomulating gradually  Primary viilus Syncytiotrophoblast trabecula arrange radially Cytotrophoblast enter trabecula  Secondary villus extra-mesoderm enter trabecula  Third class villus Fetal capillary enter the stroma

Structure of placenta Round Weight: g Diameter: 16-20cm Thickness: 1-3cm thick in center and thin in margin

Functions of placenta One important function of placenta is substance exchange between mater and fetus  Gas exchange: oxygen, carbon dioxide  Supply of nutrition  Depletion of fetal product of metabolism

VSM (vasculosyncytial membrane) ——the position of exchange VSM is comprised of  Syntrophoblastocyte  Basal membrane of syntrophoblastocyte  Stroma of villi  Basal membrane of capillary  Endothelium of capillary

The way of substance exchange Simple diffusion Facilitated diffusion Active transportion Phagocytosis

Other functions of placenta Defence function: limited Hormone synthesis  Human chorionic gonadotropin (HCG)  Human placental lactogen (HPL)  Pregnancy specific ß-glycoprotein (PS ß1G)  Human chorionic thyrotropin(HCT)  Estrogen, Progestin, Oxytocinase, heat stable alkaline phosphatase(HSAP)

Placental hormone level in pregnancy

Human chorionic gonadotropin (HCG) Detection of hCG in maternal blood and urine provides the basis for endocrine tests of pregnancy This hormone is a glycoprotein with a high carbohydrate content The molecule is a heterodimer composed of two dissimilar subunits, designated α and ß, which are noncovalently linked The ß -subunit is identical to those of luteinizing hormone (LH), follicle- stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). HCG prevents involution of the corpus luteum, the principal site of progesterone formation during the first 6 weeks

Human placental lactogen (HPL) Promote maternal lipolysis with increased levels of circulating free fatty acids. This provides a source of energy for maternal metabolism and fetal nutrition An anti-insulin or "diabetogenic" action that leads to increased maternal insulin levels. This favors protein synthesis and provides a readily available source of amino acids to the fetus A potent angiogenic hormone that may play an important role in the formation of fetal vasculature

Estrogen Estrogen Biosynthesis  The pathways of estrogen synthesis in the placenta differ from those in the ovary of nonpregnant women  Dehydroepiandrosterone sulfate (DHEA-S), secreted in prodigious amounts by the fetal adrenal glands  DHEA-S is converted to 16- hydroxydehydroepiandrosterone sulfate (16OHDHEA-S) in the fetal liver  DHEA-S and 16OHDHEA-S are converted in the placenta to estrogens that is, 17-estradiol (E2) and estriol (E3) motherfetus adrenal glands (DHEA-S) Liver (16OHDHEA-S) placenta

Fetal membrane Chorion Amnion  A double-layered translucent membrane  Become distended with fluid 胎膜外层为逐渐退化 的平滑绒毛膜 胎膜内层为羊膜， 为无血管膜

Umbilical cord Extends from the fetal umbilicus to the fetal surface of the placenta Length: 30-70cm, average : 50cm Diameter: cm Consist of 2 artery and 1 vein, Wharton jelly 羊膜 绒毛膜 脐带

Amniotic fluid Source:  early from serum dialysis  Mid-pregnancy from fetal urine  Late from fetal lung Absorse:  fetal membrane  Umbilical cord  Fetal skin  Fetal swallowing (500ml/day) Amniotic exchange: between mater and fetus 400ml/h Volume: 50ml at 12 weeks, 400ml at midpregancy, 1000ml at term

Feature of amniotic fluid pH: 7.20 Density: Contained: water(98-99%) inorganic substance organic substance(1-2%) Early transparent Late slighty turbid (Suspended matter like vernix caseosa, dropped fetal epithelial cell)

The functions of amniotic fluid Protect fetus  Move freely, allow musculoskeletal development, promote the normal growth and development of the lungs and gastrointestinal tract  Cushion the fetus, protect it from trauma  Warm, maintains temperature Protect mother  Prevent infection from genital tract

Maternal changes during pregancy Produce a series of changes Influenced by placenta hormone and neuro-endocrine Adapted to the needing of fetal growth and development

Changes of reproductive system Uterus  Capacity : 5ml ml  Weight: 50g – 1000g  Hypertrophy of muscle cells Fundus > inferior portion > cervix (contractility at delivery)  Endometrium –decidua

Blood supply  Increases 4-6times ( ml/min)  Most transported to the placenta(80-85%) Uterine contraction  Braxton hicks contraction——contraction without pain from 12-14w  Rare, irregular,and asymmetric  Intrauterine pressure: 5-25mmHg, duration <30s

Isthmus  Softer and longer (1 7-10cm)  Fomulate lower segment after 12w Cervix  Increased vascularity colored  Edema of the entire cervix soft  Hyperplasia of cervical glands cerical mucus plugs (avoiding the uterus cavity suffer from infection)

51 corpus Isthmus cervix lower segment Hypertrophy of muscle cells Fundus > inferior portion > cervix

Changes of ovary Enlarged Ovulation and new follicle is stopped Luteum produces E and P from 7 weeks of pregnancy Start to atrophy after 10 weeks of pregnancy The function is replaced by placenta

Fallopian tubes: is prolonged but not hypertrophy Vagina:  dilated and soft  violet coloration  desquamation of epithelium with more glycogen acidity pH (anti- bacteria) Vulva: pigmentation Ligaments: relaxed

Breasts Increasing in size and a nodular sensation due to the hypertrophy of the mammary alveoli The nipples larger, more deeply pigmented and more erectile Montgomery tubercles  Scattered around the areola  roundish nodules  result from the hypertrophy of the sebaceous glands

Changes of the circulation The growing uterus pushes the diaphragm upward, with the result that the heart is displaced to the left, upward and somewhat in the direction of the anterior chest wall Heart border: become enlargement, move upward, hypertrophy of cardiac muscle Heart rate: increased beat per min at the late pregnancy Heart volume: increased 10% at the late pregancy

Cardiac output Very important for fetal growth and development Increase by 30%, from 10 weeks and up to the peak at 32 weeks 80ml/bp and keeps the level to the term pregnancy

Blood pressure No obvious change in systolic pressure Mild decrease in diastolic pressure Vein pressure  No significantly changes in upper limb vein pressure  Lower limb vein pressure increased demonstrable in later months of pregnancy because of the disturbance of vein reflux  Supine hypotension syndrom: supine position for a long time--- inferior vene cava compressed---back volume ---output ---Bp ---hypotension

Changes of blood system Volume  Increased (30-45%) from 6-8 weeks  Peak at 32-34weeks, about 1500ml (including plasma 1000ml and erythrocytes 500ml--- hemodilution) ——physiologic anemia

Changes of blood component Red cell  Hb decreased 110g/L  Hct : 38%--31% WBC:  Slightly increase  Neutrophilic granulocyte increased Coagulating power of blood: Albumin: 35g/L

Urinary system Kidney  Renal plasma flow (RFP): 35%  Glomerular filtration rate (GFR): 50% Ureter: dilated ( P ) Bladder  Frequent micturation

Respiratory system R rate : slightly Vital capacity: no change Tidal volume: 40% Functional residual capacity: O 2 consumption: 20%

Gastrointestinal system Gastric emptying time is prolonged nausea The motility of large bowel is diminished constipation Liver function: unchanged

Skin The pigmentation of the areola, linea alba, vulva, occasionally irregularly shaped Brownish patches of varying size appear on the face and neck, the cloasma or the mask of pregnancy, which fortunately usually disappears after delivery

During late months of pregnancy, reddish, slightly depressed streaks often develop in the skin of abdomen Sometimes also in the skin covering the breasts and the thighs These striae gravidarum occur in about ½ of all pregnancies

Endocrine changes Pituitary ( hypertrophy)  Luteinizing/Follicle stimulating hormone  Prolactin  Thyroid stimulating hormone and Adrenocorticotropic hormone Thyroid  Enlarged (TSH and HCG )  Thyroxine and TBG free T3 T4 unchanged no hyperthyroidism occurs

Metabolic changes BMR: mildly rising Weight: from 13w increases by 350g per week, about 12.5kg during the entire pregnancy Metabolism of carbohydrate  Fasting-sugar lower due to higher insulin-secretion  Insulin-resistant factors Fat metabolism: deposit of fat increasing chareterized by a hyperlipemia and a tendency to ketosis

Protein metabolism: positive nitrogen balance Water metabolism: water-retention of about 7L Mineral metabolism: in the late months of gestation  Calcium and iron supplying---to avoid deficiency of calcium and iron

Bone, joint, and ligament Bone: no changes normally Joint and ligament: relaxin---loosening of joint and ligaments---the birth canal widened

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