PREGNANCY

Fertilization of Ovum First sperm enter the uterus to the ovarian end of the fallopian tube within 5-10 mins. 1 billion sperms deposited into vagina, only 1000-3000 succeed to reach close to the ovum. Only 1 sperm required for fertilization.

Introduction Sperm migration Fertilization occurs in ampulla of oviduct ~ 0.001 % of sperm (2000-3000) in ejaculate reach the ovum How do they get there within 5-10 minutes of ejaculation? o Flagellar action of sperm o Mocosa strands in cervical canal o Uterine contractions o Chemical attractant from ovum Capacitation Requires ~ 10 hours Female fluids remove cholesterol from sperm membranes Sperm membrane becomes more fragile Sperm viability 6 days in female reproductive tract window of opportunity = a few days before ovulation to 14 hours after

Gestation Period of pregnancy Ends with parturition (birth) Lasts 38 weeks (266 days ) 40 weeks if measured from start of last menstrual period Variable (+/- 2 weeks) Divided into 3 phases trimesters

Fertilization

Fertilization Fertilization consists in the union of the sperm with the mature ovum Fertilization of the human ovum takes place in the lateral or ampullary part of the uterine tube and the ovum is then conveyed along the tube to the cavity of the uterus- occupying 3-4 days and during which the ovum loses its corona radiata and zona striata and undergoes segmentation. Sometimes the fertilized ovum is arrested in the uterine tube, and there undergoes development, giving rise to a tubal pregnancy; or it may fall into the abdominal cavity and produce an abdominal pregnancy.

Acrosomal reaction Hyaluronidase Acrosin (a protease)

Barrier to penetration Corona radiata Zona pellucida Ovum cell membrane

Genetic events Ootid completes meiosis Male pronucleus joins female pronucleus Chromosomes line up for the first mitosis (now a zygote)

Blocks to polyspermy Fast block = depolarization of ootid membrane Slow block = cortical reaction = formation if penetrable fertilization membrane

Occasionally the ovum is not expelled from the follicle when the latter ruptures, but is fertilized within the follicle and produces what is known as an ovarian pregnancy. Under normal conditions, only 1 sperm enters the yolk and take part in the process of fertilization. At the point where the sperm is about to pierce, the yolk is drawn out into a conical elevation, termed the cone of attraction. Having pierced the yolk, the sperm loses its tail, while its head and connecting piece assume the form of a nucleus containing a cluster of chromosomes. This constitutes the male pronucleus, and associates with it there are a centriole and centrosome.

Immediately after the sperm enter the yolk, the peripheral portion of the latter is transformed into a membrane, the vitelline membrane which preventing the passage of additional spermatozoa. The male pronucleus passes more deeply into the yolk, and coincidently with this the granules of the cytoplasm surrounding it become radially arranged. The male and female pronuclei migrate toward each other, and, meeting near the center of the yolk, fuse to form a new nucleus, the segmentation nucleus, which therefore contains both male and female nuclear substance; the former transmits the individualities of the male ancestors, the latter those of the female ancestors, to the future embryo. By the union of the male and female pronuclei the number of chromosomes is restored to that which is present in the nuclei of the somatic cells. Coupling of the ovum, which contributes half the chromosomes, and the sperm, which contributes the other half of the chromosomes, creates a single cell called the zygote, which carries all of the chromosomes. About 30 hours after fertilization, the zygote begin to divided, first into 2 daughter cells called the blastomeres, and then into progressively smaller blastomeres, until at about 3 days after fertilization a 16 blastomere ball called the morula, enters the uterus.

Cell division of zygote

z.p. Zona striata p.g.l Polar bodies a. Two-cell stage b. Four-cell stage c. Eight-cell stage d,e. Morula stage

Development stages from ovum to embryo

Implantation of Blastocyst in Uterus After reaching uterus, development of blastocyst to trophoblast remains in uterus 2-5 days prior to implantation. Implantation ordinarily happens on 7-8 days. Obtain nutrition from endometrial secretions called uterine milk. Once implantation, cells proliferate rapidly along with mothers endometrium to form placenta.

Implantation Location in uterus Fundus or posterior wall usually

Role of the trophoblast Invasion of stratum functionalis Formation of the chorion (fetal placenta) Human chorionic gonadotropin (hCG) secretion

Function of Placenta Supply oxygen and nutrients Remove waste products and CO2. Provide a barrier between mother and fetus who are Genetically and immunologically different Endocrine organ (chg., estrogen and progesterone)

Placenta and Umbilical Cord Fetal placenta Maternal placenta Functions = exchange Umbilical cord 2 umbilical veins 1 umbilical vein Whartons jelly Umbilicus (navel) Mature Placenta

Hormonal Factors in Pregnancy Development of trophoblast cell secret hCG (human chorionic gonadotropin) into uterus. hCG can be measured 8 days after ovulation / beginning of implantation into endometrium. Rate of hCG rapidly rises to max (~ 8 weeks) after ovulation. hCG decreases between 16-20 weeks after ovulation.

Human Chorionic Gonadotropin (hCG) hCG prevents corpus luteum from degenerating thus it continues to secrete PROGESTERONE and ESTROGEN. This maintains integrity of uterine wall and inhibits subsequent ovulation (due to lack of FSH or LH) Birth-control pills mimic the high estrogen/progesterone levels to trick the body into thinking it is pregnant and thus inhibiting ovulation.

Function of hCG Glycoprotein (MW: 39000) = molecular structure LH Prevent normal involution of Corpus Luteum instead, increase larger quantities of estrogen and progesterone Allow endometrium to grow and store large amounts of nutrients Exert interstitial cells in male fetus to produce testosterone

Hormonal Control of Pregnancy Phase 1 Corpus luteum Oestrogen and progesterone Stimulated by luteinizing hormone (LH) from pituitary

Phase 2 Trophoblast and early placenta Produces (hCG) This has LH like effects on corpus corpus luteum

hCG is a peptide hormone Basis of most pregnancy tests (antibody) (appear in urine) Responsible for morning sickness Also a growth hormone/prolactin analogue from trophoblast (human placental lactogen, hPL)

Phase 3 The placenta becomes the dominant source of oestrogen and progesterone

Blood levels of hormones during gestation, 40 weeks

Function of Estrogen in Pregnancy During pregnancy, large amounts of estrogen is secreted i. Enlargement of uterus ii. Enlargement of breast and growth of breast glandular tissue iii. iv. Enlargement of female external genitalia Relax various pelvic ligaments to facilitate easy passage of fetus through the birth canal.

Function of Progesterone by Placenta Secreted by placenta in large amounts (10x) Develop decidual cells (nutrition) in endometrium Prevent uterine contraction Development of ovum prior to implantation Prepare breast for lactation

Function of Prolactin Milk production when oestrogen falls after parturition Inhibits FSH release and ovulation after parturition

Weight Gain during Pregnancy Fetus Placenta, amniotic fluid and membrane Maternal blood, tissue fluids, fat, etc Uterus Mammary glands Total 3kg 1.8kg 4.1kg 0.9kg 0.9kg 11kg

Parturition Process the baby is born Uterus becomes progressively excitable until strong rhythmic contraction force baby to be expelled 2 categories responsible for parturition; i. Hormonal changes increase excitability of uterine musculature ii. Mechanical changes cause by enlargement of baby

Hormonal changes Ratio of estrogen to progesterone Ratio of estrogen progesterone: beginning of pregnancy both hormones increase progressively (progesterone prevents expulsion of fetus and estrogen increase degree of uterine contractility) 7th month onwards, estrogen increase more than progesterone The estrogen to progesterone ratio responsible for the increased contractibility of uterus towards the end of pregnancy

Female hormone during pregnancy

Phases of Parturition Labor : uterine contractions that effect dilatation of cervix and force fetus through birth canal Parturition: bringing forth of young, encompass all physiological processes involved in birthing Phase 0: Prelude of Parturition Phase 1: Preparation for Labor Phase 2: Process of Labor Phase 3: Parturition Recovery

Phases of Parturition and Onset of Labor Divide 4 uterine phase: correspond to major physiological transient of myometrium and cervix during pregnancy

The phases of parturition and the onset of labor

Parturition Uterine contractility False labor ( Braxton Hicks contractions) True labor = parturition

Positive feedback theory of labor Begin 30 minutes apart progress to every 1-3 minutes cervical stretch neuroendocrine reflex oxytocin secretion uterine contraction more stretch repeat

Stages of labor

Dilation

expulsion

placental

Phase 0: Prelude to Parturition Braxton Hicks contraction or false labor: Myometrial contractions that do not cause cervical dilatation Unpredictability in occurrence Lack of intensity Brevity of duration Discomfort confined to low abdomen & groin

i.

Hormonal changes

Effect of Oxytocin on the Uterus Secreted by PP causes uterine contraction Irritation or stretching of the uterine cervix causes neurogenic reflex to PA to increase oxytocin secretion Mechanical factors

ii.

Stretch of uterine musculature Stretching of smooth muscle usually increases contractibility Fetus movement in the uterus (occuring repetitively) also elicit smooth muscle contraction

Stretch or irritation of cervix Directly elicit uterine contraction Effect from action potential of muscle from cervix to body of the uterus

Phase 1: Preparation for Labor Timings highly variable 10hours Fall in progesterone concentration (normally inhibitory) Prostaglandins - appear important in initiating contractions Fetal head pushes against cervix stimulates sensory endings Reflex release of oxytocin from posterior pituitary Begins when uterine contraction of sufficient frequency, intensity & duration o Ends when Cx is fully dilatated (10cm) o Stage of cervical effacement & dilatation Oxytocin stimulates myometrial smooth muscle (now very sensitive to oxytocin due to estrogen) Increasing contractions

1st Stage of Labor: Clinical Onset of Labor Show (bloody show) Sign of initiation of labor Spontaneous discharge of small amount of blood-tinged mucus from vagina Labor already in progress or ensure during next several hours to days Periods of relaxation between contractions Essential to welfare of fetus Unremitting contraction of uterus Compromises uteroplacental blood flow Fetal hypoxia Duration of contraction : in active phase

Duration 30-90 seconds (average 60sec) Cervical Changes Induced during 1st stage of Labor Changes induced in the cervix with labor Effective force of 1st stage of labor is uterine contraction As result of action these take place in the already ripened cervix effacement & dilatation Cx completely (fully) dilated 10 cm

Cervix near end of pregnancy, before labor

Beginning effacement of cervix

Further effacement of cervix

Cervical canal obliterated

Phase 2: Process of Labor More cervical dilatation Vaginal stretch stimulates contraction of abdominal walls Periodic contractions increase in frequency (1 every 1-3 min)

2nd stage of labor Begins when complete dilatation of cervix Ends with delivery of fetus Stage of expulsion of fetus

Phase 3: Parturition Recovery 3rd stage of labor Begins after delivery of fetus Ends with delivery of placenta and fetal membrane Stage of separation & expulsion of placenta

3rd Stage of Labor: Delivery of Placenta & Membrane Immediately after delivery & for 1 hour or so thereafter, myometrium in state of rigid & persistent contraction & retraction effect compression of large Uterus vessels severe (Post-partum Haemorrhage) PHH prevented Involution of uterus & reinstitution of ovulation Complete uterus involution: 4~6 weeks Infertility persist as long as breast feeding is continued (lactation an ovulation & amenorrhea)

Postnatal Care Lactation Milk production initiated by fall in oestrogen Reflex release of prolactin from anterior pituitary gland by stimulation of the nipple Prolactin stimulates secretion of milk Suckling cause milk ejection via oxytocin from posterior pituitary

Lactation Mature milk production not immediate on parturition Colostrum for few days Contains: Lactoferrin (antebacterial) Antibodies (provides passive immunity until neonate immune system matures)

Mature milk Contains: Lactose, fats, protein, vitamin, Ca etc

Preparation of the mammary glands during pregnancy Estrogen and other hormones causes duct growth and branching progesterone causes development of secretory acini steroid prevent milk synthesis

What happen after birth? Colostrum secreted for the 1st 3 days Placental delivery = no estrogens and progesterone secretion milk synthesis now begins

Milk ejection (let-down) reflex Tactile stimulation of nipple areolae initiates neuroendocrine reflex sensory input to hypothalamus secretion of oxytocin and prolactin from anterior gland Oxytocin stimulates contraction of myoepithelial cells around acini causing milk let down Prolactin stimulates renewed milk synthesis by acinar cells

Changes in the Mammary Glands During pregnancy Development of ducts Development of glands

Complication in Pregnancy Morning sickness ( hyper emesis) Feeling nauseous or actual vomiting (nutritional problems) Mainly due to hCG Spontaneous abortion (miscarriage) Gross malformation of fetus Maternal malnourishment Loss of progesterone (antagonist produce abortion) Damage to uterus or placenta Pregnancy induced hypertension May require abortion or premature induction of parturition Normal implantation is at top of uterus Often along sides Rarely in Fallopean tubes (maternally life threatening) Ectopic pregnancy Fallopean tubes Outside of uterus Excessive blood at parturition