NU BIOL 5541 - The Horomones of Pregnancy, Parturition and Lactation

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The Horomones of Pregnancy, Parturition and LactationIntroduction• In human the time it takes for the initial diploid cell to develop into a fully grown fetus ready to be delivered from the mother’s uterus at parturition is normallyapproximately 260-270 days• Generally divided into 3 trimesters• Formation of a placenta which will act as a vital ‘intermediary’ between the mother and growing fetus• Provide hormones which are essential for the maintenance of normal growth and development of the fetus itselfFertilization• In order to successfully fertilize an ovum, the spermatozoa need to have reached a certain stage of development, which includes the ability to swim effectivelyin their containment fluid• A contraceptive method for males is tying off the vasa deferentia, preventing the passage of spermatozoa into the urethra• Stored spermatozoa are propelled via the ejaculatory duct into the urethra, along with the fluid released from the seminal vesicles which usually representstwo-thirds of the total ejaculate volume• More fluid and useful molecules such as nutrients is provided by other accessory sex glands including the prostate which provides most of the remainder• Semen is released into the female vagina at copulation by the process of ejaculation• Contains fibrinogen and fibrinogens as well as fibrinolytic enzymes, so that when it is deposited within the vagina it rapidly clots, and then subsequentlyreturns to the fluid stage as spermatozoa are released through the cervix into the uterus itself• While in the vas deferens, the spermatozoa develop a limited capability to move by means of whiplash-like activity of their tails (activation), but they areunlikely to be able to fertilize an ovum• Full capability to move effectively and to fertilize an ovum are properties which are attained only within the female reproductive tract in the presence ofestrogens (capacitation)• Of the many spermatozoa released in the ejaculate, very few actually enter the uterus and survive the journey up to the Fallopian tube where the ovum isusually to be found after ovulation• In the presence of the ovum, the first spermatozoon to reach it binds to a glycoprotein called ZP3, on the zona pellucida membrane around the ovum• In the presence of progesterone, calcium ions enter the spermatozoon head and the inner surface of the membrane and the large enzyme-containingvesicle called the acrosome become exposed to the exterior• Another binding size on the inner membrane of the spermatozoon head binds to ZP2 on the zona pellucida surface and the spermatozoon penetratesthrough the membrane by the simultaneous release of hyaluronase and other proteolytic enzymes from the ruptured acrosome which digest their waythrough the zone, allowing it to reach the ovum surface• Ovum immediately undergoes a zonal reaction during which the second polar body is expelled• The genetic material from the spermatozoon now enters the ovum and a new diploid cell is producedImplantation and creation of the placenta• Fertilization usually takes place in a Fallopian tube• Initially the cells divide, however when the number of cells has reached approximately 16, they compact to form a spherical morula• Begin to specialize into an inner cell mass and an outer layer of trophoblast cells surrounding a fluid-filled blastocoel• From initial formation to the formation of the blastocyst, the group of developing cells is called the conceptus and it remains surrounded by the zona pellucida• As the morula becomes a blastocyst, it moves from the Fallopian tube into the uterus• The inner cell mass develops into the embryo• The trophoblast cells become extra-embryonic tissue ultimately forming part of the placenta• In humans implantation is invasive, meaning that it will penetrate into the endometrium where subsequent development takes place• Attachment phase when the trophoblast cells attach to the endometrial surface • Zona pellucida is removed by digestive enzymes secreted by the trophoblast cells and/or the endometrial glands• Attachment requires a particular endocrine environment of estrogens superimposed upon the dominant progestogen background• One key molecule involved in bringing about the apposition of the outer trophoblast cells with the epithelial cells lining the endometrium is the cytokineglycoprotein Leukemia Inhibitory Factor (LIF)• Promotes general receptivity of the endometrial lining to the approaching blastocyst, and without it implantation does not occur• More localized attachment process is brought about by various molecules including the estrogen-stimulated release of heparin-bound epidermal growthfactor (HB-EGF), the cytokine IL-11 and leptin• Within hours of the outer trophoblast cells touching the endometrial lining, they begin to infiltrate the epithelial cells and penetrate the stroma• Invading trophoblast cells lose their membranes and interconnect, forming a syncytiotrophoblast• The decidua becomes a source of nutrients for the now implanting blastocyst, in a process called decidualization• The epithelial cell layer gradually re-forms over the implanting blastocyst as it invades the endometriumHormones of pregnancy• Human chorionic gonadotrophin (hCG)• Produced by the implanting syncytiotrophoblast cells• Can be detected by the 10th day of pregnancy• Binds to the LH receptors on the luteal cells in the corpus luteum and thereby stimulates these cells to continue synthesizing estradiol and progesterone,despite the now diminished maternal LH• Concentration in the maternal blood increases to reach maximum levels around the 10th to 12th week of pregnancy after which levels decline• Estrogens• From the sixth week of pregnancy, the placenta is the source of most of the estrogens being produced, but both mother and fetus provide the necessaryprecursor molecules• The largest quantity of estrogen produced is the less-potent estriol• Measurement of urinary estrogen excretion levels can be a useful indicator of fetal well-being• Estriol precursors are provided by the fetus• Vital for the normal growth and development of the fetus throughout the pregnancy, and necessary for preparing the mammary glands by stimulating theirgrowth and development and the smooth muscle of the myometrial lining of the uterus• Stimulate the synthesis of oxytocin receptors, prostaglandins, prolactin• Effects do not actually occur noticeably until the

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NU BIOL 5541 - The Horomones of Pregnancy, Parturition and Lactation

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