Page%1%of%9%%%Lecture 10: Female Reproduction Sexual determination occurs early in the embryo. If there is SRY protein via the Y chromosome the embryo will develop as a male Lack of SRY causes the embryo to develop as a female • Gonads become ovaries • Mullerian ducts become female accessory structures; fallopian tubes (where fertilization takes place), uterus, upper 1/3 of vagina • Female is the “default” pathway of development BICD 150 Sp’14 Fortes 6 5/6/14 1 of 9Page%2%of%9%%During the fetal stage is when all of the germ cells (oocytes formed from Oogonium) are going to be generated • 7 or 8 million cells become enveloped in a primordial follicle surrounded by granulosa cells • Theca cells are separated from the follicle by a basal lamina • Each follicle contains a single oocyte • A single Oogonium will enter meiosis but be arrested before the first meiotic division • The first meiotic division will occur in oocytes that do not atrophy and are successful in being ovulated ( a very small percentage as we’ll see); it occurs just before or at the moment of ovulation o The cell has been arrested in meiosis since the embryo! It may have been waiting over 40 years to divide • Menopause is when all potential follicles have been ovulated; usually occurs in the early 50s In the embryonic stage there are 7-8 million Oogonium. They will form primordial follicles but a lot of them don’t make it and die off; a process known as atresia At birth a girl may have only 1-2million follicles remaining By the time the girl reaches puberty she has already lost a large fraction of her follicles. She has ~300-400k follicles at this point. Once menstruating, there is a competition between many follicles to develop with every cycle. Only one gets menstruated every month and the rest die off Development of follicle: The oocyte will synthesize a layer of glycoproteins on its surface called the zona pellucida Granulosa cells surround the oocyte and line the inner walls of the folliclePage%3%of%9%%Primordial Follicle-> Primary -> Secondary -> Tertiary Follicle • Involves an increase in size of the oocyte and the number and size of the granulosa cells • 1' - 3' are hormone independent development. Lasts about 300 days Tertiary follicle-> Antral follicle • Antral process requires FSH and LH • The antral period is when the granulosa cells will begin to secrete fluid and produce a fluid filled cavity called the antrum • This blister will continue to grow in the ovary • At ovulation the blister explodes releasing the liquid and the oocyte • Antral period lasts around 40 days The ovulated antral follicle can be fertilized forming a zygote. This is when the 2nd meiotic division occurs There are hundred or more follicles that begin development and perhaps reach the antral phase every month. Usually it is only one or two oocytes that get ovulated. All of the others die off. Selection of the dominant follicle is a race to maturity. Each menstrual cycle lasts ~28 days. The selection of the antral follicles starts at the end of the previous cycle What keeps the oocyte from finishing meiosis? • Meiosis is inhibited by having the granulosa cells secrete a factor called Oocyte Maturation Inhibitor (OMI) • OMI produces an increase in cAMP that can influence the oocyte and prevent the continuation of meiosisPage%4%of%9%%• What triggers ovulation is a very large surge in LH that inhibits the production of cAMP, removing the inhibition of OMI Menstrual Cycle • Day 1 usually is marked by the beginning of the menstrual flow • Menstruation is a release of dead cells from the outer part of the endometrium; the lining of the uterus • Endometrium grows under the influence of hormones. Eventually there will be necrosis of these cells and they are lost if there is no pregnancy • The menstrual cycle can be divided into to two processes happening simultaneously in the ovary and uterus that can affect each other. Uterine cycle • Proliferative phase: Is the first half of the cycle; under influence of estrogen. Growth of the endometrium after the end of menstruation • Secretory: Influenced by progesterone. Endometrium stops growing in thickness but will be stimulated to grow exocrine glands that secrete a variety of glycoproteins and glycogen. Increase in # of blood vessels/ vascularization and they become more permeable. Prepares the endometrium for potential implantation of a zygote Ovarian Cycle: • Maturation of follicle to secrete estrogens and androgens • After ovulation there will be the secretion of progesterone • Follicular phase: follicle is developing and increasing in size • Ovulation • Luteal phase: Granulosa and theca cells that remain in the ruptured follicle form the corpus luteum. Cells lose the basal lamina and secrete additional hormones including progesterone. The corpus luteum will normally die off in 10 days and stop producing hormones due to a decrease in LH. This causes a drop in estrogen and progesterone that induces menstruation. If there is a pregnancy the corpus luteum is rescued by a hormone from the implanted zygote and further menstruation is inhibited Effects of hormonal cycles on women's bodies • Measure your temperature every morning for a month. Temperature rises in the days surrounding ovulation • Properties of cervical mucus are hormone dependent. Mucous is normally viscous and thick. Under the effect of estrogen (during the first part and maximizes in the middle of the cycle) the mucous becomes very fluid allowing for sperm to enter the uterus from the cervix. Menstruation is caused by the drop in hormones estrogen and progesterone which leads to an increase in prostaglandins Decrease in E2 and Progesterone -> Increase PGF2a (vasoconstriction/uterine contraction) and PGE2 (vasodilation)Page%5%of%9%%• Vasoconstriction causes a decrease in local blood flow. This is known as Ischemia. Cells don’t get enough O2 and their metabolism accumulates reducing equivalents • If you allow blood to flow again to ischemic tissue the reperfusion will generate many free radicals and cause a lot of cell damage and cell death • Ischemia reperfusion injury is responsible for the sloughing off of the endometrium • Menstural cramps are caused by the increase in prostaglandin PGF2a. Taking an aspirin or other NSAID will inhibit the enzyme COX so prostaglandins cannot be made. They must be