2The female pathway is the default setting In the absence of SRY, the primitive gonad automatically differentiates as female.In the absence of testosterone (or other androgen), the Wolffian system deteriorates.In the absence of Mullerian inhibiting factor, the Mullerian structures automatically form the Fallopian tubes, uterus and inner 2/3 of the vagina.
3In the absence of androgen, the external genitalia differentiate as female
4The X chromosome and disorders of chromosomal sex XO: Turner’s syndrome – female gonadal sex and female body plan – ovaries do not differentiate beyond the primitive streak stage – no growth spurt, no fertility, feminizing puberty and sustained feminine characteristics must be sustained by exogenous estrogen.XXX “superfemale” – essentially normal female sexual differentiation but reduced fertility.
5The adrenogenital syndrome in XX genotype Excess DHEA is present during fetal life – various causes including 21 hydroxylase deficiency in fetus or mother, maternal adrenal tumor, maternal hyperadrenalismGenerally, the extra androgen comes too late to preserve the Wolffian system, but can result in partial or total masculinization of the external genitaliaA somewhat masculinized body style is typical – some investigators have associated this with a “tomboy” set of behaviors.
6Female pubertyIncrease in secretion of Gnrh leads to increase in LH and FSH secretion – menarche – menstrual cycles begin.At puberty, ovaries contain about 400,000 primary follicles, each containing a primary oocyte arrested at 1st meiotic metaphase.Each cycle leads to initiation of maturation of about 1,000 primary follicles. Of these, only one or two (in humans – more in animals that typically have multiple births) reach the stage of ovulation – the others are eliminated by a process called atresia.
7The mean age of menarche in N The mean age of menarche in N. European populations has fallen steadily over the past two centuries
8Maturing Follicles are the sources of ovarian steroid During the period of follicle maturation (follicular phase) in each cycle, theca cells (outer layer; homologues of Leydig cells, so controlled mainly by LH) of each follicle produce androgen (androstenedione).Androgen is exported to the granulosa cells (inner layer; homologues of Sertoli cells, so controlled mainly by FSH) for conversion to estradiol, the major form of estrogen secreted by the ovary.After ovulation, the remnants of the follicle form a corpus luteum that secretes both estradiol and progesterone during the luteal phase of the cycle.
9Ovarian sterol biosynthesis involves collaboration between theca cells and granulosa cells LHFSHGranulosa cellTheca cellcholesterolcholesterolprogesteroneandrostenedioneandrostenedioneestradiol
10Effects of estrogen at puberty Establishes female pattern of body fat deposition, bone growth and body hairStimulates growth of external and internal genitaliaStimulates breast maturation, particularly the ductal systemStimulates growth of uterine endometrium, particularly during the follicular phase of the menstrual cycle
11The female cycle takes place on multiple anatomic levels Ovarian: follicular – lutealPlasma: levels of FSH, LH, estradiol, progesterone and inhibinUterine endometrium – proliferative – secretory - menstrualCervical/Vaginal: impenetrable mucus/acid pH – watery mucus, alkaline pHBehavioral: humans: subtle sexual interest variations over the cycle. Other mammals: estrogen leads to estrus behavior.
14The control relationship between hypothalamus, ant The control relationship between hypothalamus, ant. pituitary and ovary changes over the cycleA complete cycle can occur if the hypothalamus just releases Gnrh in regular pulses – therefore the hypothalamus does not organize the cycle.The pituitary can organize the cycle but to do so it must have a dialogue with the ovary.As estrogen levels rise, the pituitary switches from decreasing LH and FSH release in response to estrogen (negative feedback) – to increasing FSH and LH release in response to estrogen – a positive feedback that leads to a spike of gonadotropins as the follicle matures.
15Control of ovarian function HypothalamusGnrhinhibinAnt.pituitaryestradiolFSHLHOvariesFollicularization Estrogen secretionOvum maturation
16OvulationIn the human pattern,ovulation is triggered around day 14 of the cycle by a sharp rise in plasma gonadotropinsThe oocyte is surrounded by a corona radiata of follicular cells
18The Uterine cycleThe endometrium consists of a functional layer that contains stem cells, and a differentiated decidual layer that can be shed periodicallyDuring the follicular phase of the ovary, estradiol causes the uterine lining to proliferate and thicken.During the luteal phase, the addition of progesterone causes the endometrium to develop additional vascular elements, and spiral glands that secrete nutrients (uterine milk) into the uterine lumen – during this phase, the endometrial conditions are ideal for implantation of a zygote. A state of pseudopregnancy exists in this period.Shedding of the decidual layer – menstruation - results from the sudden drop in plasma levels of estradiol and progesterone as the corpus luteum becomes a corpus albicans.
19MenopauseIn humans, menopause occurs in the age range of years. Menopause is not a common phenomenon in non-human mammals.At menopause, it appears that the initial stock of primary follicles has been exhausted – a dominant hypothesis argues that follicle exhaustion determines the timing of menopause.However, reduction of cycle number by use of hormonal birth control does not delay menopause, so follicle atresia must steadily eliminate follicles whether cycling is occurring or not.The onset of menopause is accompanied by a large rise in the plasma levels of gonadotropins, arguing that the hypothalamus and pituitary do not initiate menopause by shutting down ovarian function
20Hormonal contraception Site and mechanism of action of hormonal contraceptive depends on the hormonal constituents and their dosages (i.e. estrogen. estrogen+progesterone, progesterone only)Potentially, exogenous steroids could interfere with:Gnrh secretionGonadotropin secretionEgg/sperm transport in Fallopian tubeVaginal/cervical environmentImplantation of zygote