FISIOLOGI PERTUMBUHAN JANIN DAN FAKTOR YANG MEMPENGARUHI Rahmatina B. Herman Bagian Fisiologi Fakultas Kedokteran Universitas Andalas Fertilization Definition: the union of male and female gametes Can take place during fertile period in each cycle Normally occurs in ampulla Thus, both ovum and sperm must be transported from their site of production to the ampulla During first 3-4 days following fertilization, zygote remains within ampulla, because of constriction between ampulla and remainder oviduct canal prevents further movement of zygote into uterus A number mitotic cell divisions of zygote to form morula during in ampulla Descent of Morula to Uterus ± 3-4 days after ovulation, progesterone produce is sufficient to relax oviduct contraction morula rapidly propelled into uterus by oviductal peristaltic and ciliary activity Temporary delay of descending embryo into uterus, lets enough nutrients accumulate in uterine lumen to support embryo until implantation can take place Morula will die, if it arrives prematurely ……Descent of Morula to Uterus Morula floats freely within uterine cavity for 3-4 days, living on endometrial: - secretions and continuing to divide - being prepared for implantation under influence of luteal-phase progesterone - storing up glycogen - becoming richly vascularized Morula which fails to descend into uterus will lead to ectopic tubal pregnancy (95% of ectopic pregnancy) Implantation ± 1 week after ovulation, morula has descended into uterus and continued to proliferate and differentiate into blastocyst which capable to implantation Blastocyst is consisted of 2 parts: inner cell mass (which become fetus) and trophoblast (outermost layer of blastocyst) Trophoblast accomplish implantation, after which develops into fetal portion of placenta When blastocyst is ready to implant, its surface becomes sticky, by the time endometrium is ready to accept the early embryo Formation of Placenta and Amniotic Sac By day 12: - embryo is completely embedded in decidua trophoblastic layer (2 cell layers) thick chorion Chorion continues to release enzymes and expand - forms extensive network of cavities within decidua erodes decidual capillary walls maternal blood leaks and fills the cavities produces anticoagulant to keep blood clotting Developing embryo sends out capillaries into chorionic projections to form placental villi …..Formation of Placenta and Amniotic Sac Each placental villus contains embryonic/ fetal capillaries surrounded by a thin layer of chorionic tissue, which separates the embryonic/fetal blood from maternal blood in intervillus spaces barrier All exchanges between fetal and maternal bloodstreams take place across the extremely thin barrier …..Formation of Placenta and Amniotic Sac Entire system of interlocking maternal (decidual) and fetal (chorionic) structures makes up the placenta By 5 weeks after implantation: - Placenta is well established and operational (even though not fully developed) - Heart of developing embryo is pumping blood into placental villi as well as to embryonic tissues Placenta Specialized organ of exchange between maternal and fetal blood Derived from: - trophoblastic tissue, and - decidual tissue Function: to sustain the growing embryo / fetus during intrauterine life Functions of Placenta Transport system between maternal blood and fetal blood: - Nutrition & O2 and metabolic wastes & CO2 - Drugs, pollutants, cigarette smokes, chemical agents, microorganisms harmful (thalidomide, AIDS, drug abuse) Temporary endocrine organ: Fetally derived portion has remarkable capacity to secrete peptide and streoid hormones for maintaining pregnancy Placental Hormones HORMONES FUNCTION 1. Human chorionic gonadotropin (hCG) - Maintains CL of pregnancy - Stimulates secretion of testosterone by developing testes in XY embryo 2. Estrogen - Stimulates growth of myometrium, increasing uterine strength for parturition - Helps prepare mammary glands for lactation 3. Progesterone - Suppresses uterine contraction to provide a quiet environment for fetus - Promotes formation of cervical mucus plug to prevent uterine contamination - Helps prepare mammary glands for lactation …..Placental Hormones HORMONES FUNCTION 4. Human Chorionic - Believed to reduce maternal use of glucose and to Somatomammo promote breakdown of stored fat so that greater tropin (hCS) similar quantities of glucose and free fatty acids may be to GH and prolactin shunted to fetus - Helps prepare mammary glands for lactation 5. Relaxin - Soften cervix in preparation cervical dilation at parturition - Loosens connective tissue between pelvic bones in preparation for parturition 3. Placental PTHrp (Parathyroid Hormone-related peptide) - Increases maternal plasma Ca2+ level for use in calcifying fetal bones, if necessary promotes localized dissolution of maternal bones, mobilizing their Ca2+ stores for use by developing fetus Preventing Rejection of Embryo Theory I: • Trophoblast produce Fas ligand which binds with Fas, a specialized receptor on surface of approaching activated maternal cytotoxic T cells (immune cells that carry out the job of destroying foreign cells) • The binding triggers immune cells that are targeted to destroy the developing foreigner to undergo apoptosis, sparing embryo/fetus from immune rejection …..Preventing Rejection of Embryo Theory II: • Fetal portion of placenta which derived from trophoblast produce enzyme indoleamine 2,3dioxygenase (IDO) which destroy tryptophan (critical factor in activation of maternal cytotoxic T cells) Theory III: • In pregnancy production of regulatory T cells is doubled or tripled which suppress maternal cytotoxic T cells Growth and Functional Development of Fetus Initial development of placenta and fetal membranes occurs far more rapidly than development of fetus 2-3 weeks after implantation of blastocyst, the fetus remains almost microscopic in size But thereafter the length of fetus increases in proportion to age: - At 12 weeks : 10 cm - At 20 weeks : 25 cm - At 40 weeks (at term) : 53 cm Development of Organ Systems Gross characteristics of different organs: - Within 1 month after fertilization begun to develop - During the next 2-3 months, most of details are established - Beyond the 4th month: mainly the same as those of the neonate Cellular development in each organ is usually far from complete: - Requires the full remaining 5 months for complete development - Even at birth certain structures (nervous system, kidneys, and liver) lack full development Circulatory System Heart: Begins beating during the 4th week after fertilization ± 65 bpm and increases to ± 140 bpm before birth Blood cells: - During the midportion of fetal life: Extra marrow areas are the major sources of blood cells - During the latter 3 months of fetal life: Bone marrow gradually take over, while other areas lose their ability, except for lymphocytes and plasma cells produce in lymphoid tissue Respiratory System Respiration cannot occur during fetal life At the end of 1st trimester of pregnancy: respiratory movements caused by tactile stimuli or fetal asphyxia During the latter 3-4 months of pregnancy for unclearly reasons: - Respiratory movements are inhibited - Lungs remain almost completely deflated - It prevents filling of lungs with debris from meconium - Fluid is secreted into the lungs by alveolar epithelium up until birth → keeping only clean fluid in the lungs Nervous System Most of skin reflexes are present by 3rd – 4th month of pregnancy However, functions of central nervous system that involve cerebral cortex are still mainly undeveloped, even at birth Myelinization of some major tracts of central nervous system becomes complete only after ± 1 year of postnatal life Gastrointestinal Tract By midpregnancy: fetus ingests and absorbs large quantities of amniotic fluid During the last 2-3 months: gastrointestinal function approaches that of normal neonate Small quantities of meconium are continually formed in gastrointestinal tract and excreted from bowel into amniotic fluid Meconium is composed of: - Residue from amniotic fluid - Excretory products from gastrointestinal mucosa and glands The Kidneys Fetal kidneys are capable of excreting urine during at least the latter half of pregnancy and urination occurs normally in utero However, renal control systems for regulating: - Extracellular fluid electrolytes balances - Acid-base balance are almost nonexistent until after midfetal life and do not reach full development until a few months after birth Fetal Metabolism Fetal uses mainly glucose for energy Fetal has a high rate of storage of fat and protein Most of fat being synthesized from glucose, rather than being absorbed from mother’s blood Some special problems of fetal metabolism in relation to: - Calcium and phosphate - Iron - Some vitamins Metabolism of Calcium and Phosphate ± 22.5 gr of calcium and 13.5 gr of phosphorus are accumulated during gestation: ± ½ of it accumulates during the last 4 weeks of gestation which is coincident with the period of rapid ossification of fetal bones as well as rapid weight gain During the earlier part of fetal life, fetal bones are relatively unossified and have mainly cartilagous matrix until ± 4th month of pregnancy Total amount of calcium and phosphate needed during gestation represent only ± 1/50 quantities of these substances in mother’s bone → minimal drain from mother A much greater drain occurs after birth during lactation Metabolism of Iron Iron accumulates in fetus more rapidly than calcium and phosphates Most of iron is in the form of Hb, which begin to be formed at 3rd week after fertilization Small amounts of iron are concentrated in mother’s uterine progestational endometrium even before implantation, which then ingested into embryo by trophoblastic cells for early formation of RBC ± 1/3 of iron in a fully developed fetus is stored in liver that can be used for several months after birth Metabolism of Vitamins Fetus needs vitamins equally as much as adult and in some instances to a far greater extent Vitamins function the same in fetus as in adult: - Vit B: especially B12 and folic acid for formation of RBC and nervous tissue as well as for overall growth - Vit C: for appropriate formation of intercellular substances, especially bone matrix and fibers of connective tissue - Vit D: probably for normal bone growth in fetus But more important for adequate absorption of calcium from mother’s gastrointestinal tract → large quantities will be stored by fetal liver to be used for several months after birth …..Metabolism of Vitamins - Vit E: necessary for normal development of early embryo although the mechanisms are not clear In its absence in laboratory animals: spontaneous abortion usually occurs at an early age - Vit K: for formation of Factor VII, pro-thrombin, and several other blood coagulation factors When vit K is insufficient in mother: Factor VII and prothrombin become deficient in fetus as well as in mother Because most vit K is formed by bacterial action in colon, neonate has no adequate source of vit K → prenatal storage in fetal liver derived from mother is helpful in preventing hemorrhage, particularly when head is traumatized by squeezing through birth canal