Module 9: Reproductive System Flashcards
1
Q
• process of genetic inheritance that sets the gender of an individual at the moment of fertilization
A
SEX DETERMINATION
2
Q
• development of differences between males and females from an undifferentiated zygote
A
SEX DIFFERENTIATION
3
Q
• sequential processes of establishment of sex and sexual difference • includes the processes that determine: o CHROMOSOMAL or GENETIC SEX o GONADAL SEX o PHENOTYPIC or GENITAL SEX o PSYCHOLOGICAL SEX
A
Sex Determination and Differentiation
4
Q
• established by genetic inheritance at the moment of fertilization
A
Chromosomal Sex
5
Q
- development of primary sex organs (gonads) in response to genetic sex
- If you are a male/female, you should have an organ that tells you that your a male/female (testis/ovary)
A
Gonadal Sex
6
Q
• a chromosome that determines the maleness
A
Y chromosome
7
Q
Gonadal Sex (Male)
A
Sex-determining region of Y chromosome (SRY) codes for production of testis-determining factor (TDF)»_space; TDF directs differentiation of gonads into TESTES
8
Q
Gonadal Sex (Female)
A
No Y chromosome»_space; No, Sex-determining region of Y chromosome (SRY) and testis-determining factor (TDF)»_space; undifferentiated gonads develop into OVARIES
9
Q
- regulation by gonadal sex of the differentiation of the genital apparatus
- influenced mainly by genetics and hormonal factors
- determines by the presence or absence of a masculinizing hormone (testosterone)
A
Phenotypic or Genital Sex
10
Q
- secretes testosterone and Mullerian-inhibiting factor (anti-mullerian hormone)
- transforms Wolffian ducts into internal male reproductive system
- can be converted to dihydrotestosterone that promotes the development of undifferentiated external genitalia among male lines (penis, scrotum)
A
Testosterone
11
Q
• where the development of the internal female reproductive tract came from (eg Oviducts, Uterus)
A
Mullerian duct
12
Q
• causes the degeneration of the Wolffian ducts and development of undifferentiated external genitalia along female lines (eg Clitoris, labia)
A
Absence of Testosterone
13
Q
- establishment of gender role, gender identity or sexual orientation
- influenced by behavioral and cultural factors
A
Psychological Sex
14
Q
• determined at time of fertilization when ovum and sperm unite
- genetic male (heterogametic ) = XY pattern
- genetic female (homogametic) = XX pattern
• mutation of genes on an X chromosome results in transmission of X-linked traits
*EXAMPLES: hemophilia, color blindness
A
Genetic Sex
15
Q
• presence of the Y chromosome is the single most consistent determinant of maleness
- contains SRY gene responsible for sex determination
- necessary for testes and masculine genital pattern development
A
Genetic Sex
16
Q
• presence of additional X chromosome does not alter fundamental maleness dictated by the Y chromosome
*EXAMPLE: Klinefelter Syndrome (XXY)
A
Genetic Sex
17
Q
• discovered by Barr and Bertram in 1949
• one of the two copies of the X chromosome present in females is inactivated (Lyon hypothesis)
*nucleus of somatic cells of females contain a plano-convex mass adherent to inner side of nuclear membrane (sex chromatin mass or Barr body)
A
Sex Chromatin Test
18
Q
(Sex Chromatin Test)
• presence of 1 Barr body means that an individual has 1 X chromosome in excess (2 X chromosomes total)
A
Normal Female
19
Q
(Sex Chromatin Test)
• presence of 2 Barr bodies means that an individual has 2 X chromosomes in excess (3 X chromosomes total)
A
Superfemale
20
Q
Specimens for Sex Chromatin Test
A
• NERVE CELLS • BUCCAL SMEAR (inner cheek scrapings) - if 20% positive, genetic female - if 0-4% positive, genetic male (4% error margin) • BLOOD SMEAR - presence of drumstick appendage in nucleus of neutrophils in genetic females - low positiveness (6/500 neutrophils) • VAGINAL SMEAR
21
Q
• form of genetic imprinting where one of the two chromosome is inactivated so that the only one is active
A
Lyonization
22
Q
• pluck 3-4 strands of normal scalp hair
- tease the root of hair
- stain with fluorescent stain
- look for fluorescent body (Y body)
- part of the Y chromosome present only in males (15/100 cells) and invariably absent in females
A
Hair Root Test
23
Q
• noninvasive screening for large populations in sports competitions (eg, Olympics)
- assurance that individual joining female division sports competition is a normal genetic female
A
Hair Root Test
24
Q
- patient has a testes and produce testosterone but despite the presence of it, it lacks of receptor for testosterone
- due to high testosterone, pt is masculine
- pt is genetically male but due to the absence of penis, pt can be mistaken as a female
A
Androgen Insensitivity Syndrome
25
* requires use of tissue culture (may take 10 days for complete processing)
* most accurate method (gold standart)
* done by geneticists
* required for patients who will undergo gender reassignment surgery (genetic sex must be determine for those who want gender reassignment or those with ambiguous genitalia)
Karyotyping
26
What are the 3 tests for genetic sex?
* Sex Chromatin Test
* Hair Root Test
* Karyotyping
27
• development of primitive gonad into either testes or ovary
- outer cortex composed of COELOMIC EPITHELIAL CELLS
- inner medulla composed of STROMAL MESENCHYME which surrounds cords of epithelial cells
• at 4th to 6th week of gestation, all embryos have bipotential gonads (potential to differentiate along either male or female lines)
Gonadal Sex
28
Testis-determining SRY protein initiates the production of multiple gonad medulla to differentiate into a testis which has __.
*In males, only medulla will develop and the cortex will regress.
Leydig Cells and Sertoli Cells
29
• secrete testosterone which controls the development of Wolffian duct into accessory structures and development of external genitalia via DHT
Leydig Cells
30
• secrete Anti-mullerian hormone that causes regression of Mullerian duct; responsible for the nutrition of the spermatogonia
Sertoli Cells
31
(Male Gonadal Development )
| • embryonic __ enlarges to become the testis and embryonic cortex regresses
medulla
32
(Male Gonadal Development )
* formation of seminiferous tubules and Sertoli cells at 6 to 7 weeks
* formation of Leydig cells at 8 to 9 weeks
- secrete testosterone in response to HCG
- at 9 weeks, a definitive testes is present and secretion of testosterone established
• at 7 to 9 months gestation
- testes normally descend through inguinal ring
33
Female Gonadal Development (1)
• embryonic cortex proliferates to become the ovaries
- at weeks 11 and 12, primordial follicles are discernible
- reaches maximal development by weeks 20 to 25
34
Female Gonadal Development (2)
* embryonic medulla regresses and becomes the hilum of mature ovaries
* embryonic ovary does not secrete hormones
* development starts during 9th week gestation in the absence of a signal for testis formation
35
Phenotypic Sex development requires:
- differentiation of genital ducts (internal genitalia)
- differentiation of external genitalia
- hypothalamic differentiation
36
• differentiation of the internal and external genitalia requires presence of hormones or chemical messengers
Phenotypic Sex
37
(Control Mechanisms in Development of Phenotypic Sex)
* cells in distant endocrine gland secrete hormones into bloodstream to regulate or induce differentiation in distant target tissues
* EXAMPLE: testosterone, secreted by fetal Leydig cells, induces differentiation of anlagen of external genitalia
CLASSIC ENDOCRINE MECHANISM
38
(Control Mechanisms in Development of Phenotypic Sex)
* dissemination of hormone by local diffusion through the nearby target tissue
* EXAMPLES: action of MIF on Mullerian duct, action of Testosterone on Wollfian duct
LOCAL PARACRINE REGULATORY MECHANISM
39
(Differentiation of Internal Genitalia)
| • at 7 weeks, fetus contains both male and female primordial genital ducts:
1. Wolffian ducts (mesonephric duct)
| 2. Mullerian ducts (paramesonephric ducts)
40
- have the potential of differentiating into:
• epididymis
• vas deferens
• seminal vesicles
Wolffian ducts (mesonephric duct)
41
```
- serves as the anlagen of the:
• uterus
• fallopian tube
• cervix
• upper vagina
```
Mullerian ducts (paramesonephric ducts)
42
* it doesn't mean that because you are a female you will have a uterus; you might have a congential absence of the uterus
* you did not have a mullerian duct
* 2nd/3rd common cause of the absence of menses in a teenage girl
Mayer-Rokitansky-Küster-Hauser syndrome
43
(Hormones Involved in Sex Differentiation)
• responsible for differentiation of Wolffian ducts to male internal genitalia at 9 to 10 weeks
• secreted by fetal Leydig cells
• does NOT have to be converted to its active product (dihydrotestosterone) to act on the Wolffian ducts
*5- reductase activity is required for conversion of testosterone to dihydrotestosterone
*cells do not develop 5- reductase activity until they have fully differentiated
TESTOSTERONE
44
(Hormones Involved in Sex Differentiation)
• other names: Anti-Mullerian Hormone (AMH), Mullerian Regressing Factor (MRF)
• glycoprotein hormone produced by Sertoli cells
• induces dissolution of Mullerian ducts, therefore inhibiting differentiation of female internal genitalia
MULLERIAN INHIBITING FACTOR (MIF)
45
Differentiation of External Genitalia
* in contrast to internal genitalia, external genitalia in both sexes develop from common anlagen
* growth and development of the male external genitalia require dihydrotestosterone
46
(Anlagen of External Genitalia)
* in males: becomes glans penis, corpus cavernosum and corpus spongiosum
* in females: becomes clitoris and vestibular bulb
GENITAL TUBERCLE
47
(Anlagen of External Genitalia)
* in males: fuse around the urethral groove to form the penis (ventral shaft)
* in females: genital folds do not fuse and develop into labia minora
GENITAL FOLDS or URETHRAL FOLDS
48
(Anlagen of External Genitalia)
* in males: fuse to form scrotum and prepuce
* in females: do not fuse but develop into labia majora
GENITAL SWELLING or LABIO SCROTAL SWELLING
49
(Anlagen of External Genitalia)
* in males: develops into male urethra, Cowper’s glands and prostate gland
* in females: develops into female urethra, lower vagina, Bartholin’s glands and Skene’s glands
UROGENITAL SINUS
50
Special Considerations
* in normal females, hormones may not be essential for differentiation
* growth of labia to normal size requires estrogen
51
Special Considerations (2)
• exposure of normal female fetus to excess testosterone during differentiation causes virilization
* if exposed early, male pattern can result
* if exposed after differentiation is completed, enlargement of clitoris may occur
• for newborn with ambiguity of external genitalia
* postpone signing of birth certificate
* do screening test
52
(Hypothalamic Differentiation)
| • control of gonadal function is mediated by 2 gonadotropins:
o follicle-stimulating hormone (FSH)
| o luteinizing hormone (LH)
53
(Hypothalamic Differentiation)
| • gonadotropins differ in pattern of secretion:
o in males: pulsatile but relatively constant, sustained manner (tonic release)
o in females: pulsatile but cyclic (cyclic release)
54
(Hypothalamic-Pituitary-Gonadotropin Unit)
| • includes the following:
o pulsatile secretion of (Luteinizing Hormone Releasing Hormone) LHRH by hypothalamus
o pulsatile secretion of Follicle stimulating hormone (FSH) and Luteinizing Hormone (LH) by pituitary
55
(Hypothalamic-Pituitary-Gonadotropin Unit)
| • characteristics:
o matures in the fetus
o suppressed during childhood
o reactivated at onset of puberty
56
Gonad (Cortex)
Male: Regresses
Female: Ovaries
57
Gonad (Medulla)
Male: Testis
Female: Regresses
58
Wolffian Duct (mesonephric duct)
Male: Epididymis, Vas Deferens, Seminal Vesicle
Female: Regresses
59
Mullerian Duct (paramesonephric duct)
Male: Regresses
Female: Fallopian tubes, uterus, cervix, vagina (upper 1/3)
60
Genital Tubercle
Male: Glans penis, corpus cavernosum/ spongiosum
Female: clitoris, vestibular bulb
61
Genital Folds
Male: Penis (ventral shaft)
Female: Labia minora
62
Genital Swelling
Male: Scrotum, prepuce
Female: Labia majora
63
Urogenital Sinus
Male: Male urethra, cowper's gland, prostate gland
Female: Female urethra, lower vagina, Bartholin's gland, Skene's gland
64
Defect in the fusion of the genital fold will result to an orifice in the ventral portion of the penis which is called __
Hypospadia
65
If the baby is genetically female but exposed to high levels of testosterone in utero, what will be the result?
Labia minora will fuse (Labial fusion)
66
* identification of self as either male or female
* applicable only to humans
* formed in early childhood
* independent of hormonal regulation and even of the phenotype of the individual
* depend on rearing cues and cultures
* considered as socially, culturally, historically and psychologically determined
Psychological Sex or Gender Identity
67
* exact biologic basis has not been discovered
| * region Xq28 of the X chromosome has been controversially dubbed as the “gay gene”
Homosexuality
68
(Homosexuality)
| • brain studies reveal:
o 1.7x larger superchiasmatic nucleus in homosexual males
| o anterior commissure is 18% larger in heterosexual females and 34% larger in heterosexual males
69
* established defect in gametogenesis
| * chromosomes fail to separate therefore both go to one of the daughter cells during meiosis, the other has none
Nondisjunction
70
• complete absence of one sex chromosome (Barr body)
*leads to monosomy X (XO genotype)
• short stature (
Turner Syndrome (Monosomy X)
71
* meiotic nondisjunction leads to a 47, XXY genotype
* testicular atrophy
* eunuchoid body shape
* tall, long extremities
* gynecomastia
* female hair distribution
Klinefelter Syndrome
72
* only one X chromosome is active (two Barr bodies are present)
* usually no distinguishable difference between triple X and normal females (some studies show increased risk for menstrual irregularities and learning disorders)
Superfemale (Triple X Syndrome)
73
* disorder of sexual differentiation
| * born with both ovarian and testicular tissues
Hermaphroditism
74
Hermaphroditism: two types
* true hermaphrodites - functional gonads
| * pseudohermaphrodites - phenotype and genotype do NOT match (nonfunctional gonads)
75
* genetic males whose target cells lack receptors for testosterone are feminized
* male pseudohermaphrodites (male genotype, female phenotype)
Testicular Feminization (Androgen Insensitivity)
76
• adrenal androgen overproduction in the fetus
• female pseudohermaphrodites
*female genotype, male phenotype
*virilization of an XX fetus
*ambiguous genitalia
• lack of testosterone (cortisol pathway is not favored but only the androgen pathway is favored)
Congenital Adrenal Hyperplasia (Adrenogenital Syndrome)
77
* only hormone that can produce a negative feedback in the hypothalamus-pituitary
* because of lack of this hormone, there is a continuous production of ACTH causing virilization
Cortisol
78
The two most basic components of the reproductive system are __.
the gonads and the reproductive tract
79
The gonads (testes and ovaries) perform an endocrine function, which is regulated within a __. The gonads are distinct from other endocrine glands in that they also perform an exocrine function (gametogenesis).
hypothalamic-pituitary-gonadal axis
80
Most common problem in lack of estrogen is __.
nondevelopment of the breast bud
81
The __ is involved in several aspects of gamete development, function, and transport and, in women, allows fertilization, implantation, and gestation.
reproductive tract
82
Male Reproductive System: 3 FUNCTIONS
* Spermatogenesis
* Performance of the male sexual act
* Regulation of male reproductive function through hormones (Hormones also affect cellular metabolism and growth)
83
(Male Reproductive Tract)
- Contains Seminiferous tubules
TESTIS
84
(Male Reproductive Tract)
- Coiled tube of 6 meters long
- Enables motility of sperm (for 18-24 hours
EPIDIDYMIS
85
(Male Reproductive Tract)
- Ampulla of the vas deferens
- Stores sperm
VAS DEFERENS
86
(Male Reproductive Tract)
- Walnut-shaped
PROSTATE GLAND
87
(Male Reproductive Tract)
- Forms the EJACULATORY DUCT with the ampulla of the vas deferens
SEMINAL VESICLES
88
(Male Reproductive Tract)
- External connection of testis to the external environment
- Supplied with mucus derived urethral glands and bulbourethral glands
URETHRA
89
* Formation of sperm
* Occurs in the seminiferous tubules
* Starts at puberty at around 13 years and occurs throughout life
SPERMATOGENESIS
90
Tract of Sperm
Testis (seminiferous tubules) >> epididymis >> vas deferens >> ejaculatory duct >> urethra >> out to the penis
```
SEVENUP
Seminiferous tubules
Epididymis
Ejaculatory Ducts
(Nothing)
Urethra
Penis
```
91
MEIOSIS
* Primordial germ cell originates from the primary ectoderm and migrates to the yolk sac; eventually, it finds its way into the testis
* Spermatogonia undergoes mitotic divisions, upon crossing the barrier to the Sertoli layer, enlarges and becomes primary spermatocytes.
* Primary spermatocytes undergo Meiosis I to become secondary spermatocytes
* Secondary spermatocytes undergo Meiosis II to become spermatids
* Formation of mature sperm cell from spermatids
92
• final product of meiosis
Spermatid (4 Spermatid)
93
MEIOSIS (2): Male
1. Meiosis I is the separation of homologous chromosomes
2. Meiosis II is the separation of sister chromatids
3. Duration of entire process: 74 days
94
(HORMONES AFFECTING SPERMATOGENESIS)
- Growth and division of spermatogonia
Testosterone
95
(HORMONES AFFECTING SPERMATOGENESIS)
- stimulates secretion of testosterone
Luteinizing Hormone (LH)
96
(HORMONES AFFECTING SPERMATOGENESIS)
- Conversion of spermatids to sperm (spermiogenesis)
Follicle-Stimulating Hormone (FSH)
97
(HORMONES AFFECTING SPERMATOGENESIS)
- formed from testosterone by the Sertoli Cells; probably essential for spermatogenesis
Estrogens
98
(HORMONES AFFECTING SPERMATOGENESIS)
- Background metabolism of the testis
Growth Hormone (GH)
99
What cells respond to the luteinizing hormone?
Leydig Cells
100
SEMEN: Composition
10%: Sperm from vas deferens
60%: fluid from seminal vesicles
- Contains fructose, citric acid, prostaglandins and fibrinogen
- Reacts with female cervical mucous
- Causes reverse peristalsis in female genital tract
30%: fluid from prostate gland
- Calcium, citrate, phosphate, clotting enzyme and profibrinolysin
- Alkalinizes the semen
Trace amounts from mucous glands and bulbourethral glands
101
CAPACITATION
1. Uterine and fallopian tube fluids wash away inhibitory factors of sperm
2. Sperm loses cholesterol cap
3. Sperm membrane becomes more permeable to calcium
102
- Enables the sperm to penetrate the ovarian granulosa cells
| - Mediated by hyaluronidase and proteolytic enzymes
ACROSOME REACTION
103
FACTORS AFFECTING MALE FERTILITY
1. Temperature (i.e. cryptorchidism) - increase longevity in a cooler environment
2. Sperm Count
Normal: 35M-200M/mL
Abnormal:
104
Normal semen analysis value
```
Volume: 2-5 ml
Concentration: >20 million/ml
Motility: >50%
Normal forms: >30%
pH: 7.2-7.8
```
105
(MALE SEXUAL ACT)
* Male sexual act results from inherent reflex mechanisms integrated in the sacral and lumbar spinal cord
* Sexual Sensation signaling: Glans Penis >> Pudendal Nerve >> Sacral Plexus in Spinal Cord >> Undefined areas in the brain
* May also be caused by internal structures such as bladder, prostate
* Psychic stimuli can also enhance ability to engage in sexual act
NEURONAL STIMULUS
106
STAGES OF MALE SEXUAL ACT
1. Penile Erection
2. Lubrication
3. Emission and Ejaculation
4. Resolution
107
- Due to the parasympathetic nervous system
- Release of nitric oxide which activates guanylyl cyclase
- cGMP relaxes the arteries of the penis
Penile Erection
108
- Due to parasympathetic nervous system
| - Causes the bulbourethral glands to secrete mucus
Lubrication
109
- Due to sympathetic nervous system (T12-L2), hypogastric and pelvic sympathetic nerve plexus
- Emission: contraction of the vas deferens and ampulla to cause expulsion of sperm into urethra
- Ejaculation: wave-like and rhythmical contraction of urethra to expel semen to the external environment
Emission and Ejaculation
110
- Erection ceases
Resolution
111
* Any hormone that has masculinizing effects
| * Testosterone, dihydrotestosterone and androstenedione
ANDROGENS
112
EFFECTS OF TESTOSTERONE (1-6)
1. Causes development of male external genitalia
2. Causes descent of testis
3. Development of adult primary and secondary sexual characteristics
4. Growth of hair
5. Baldness
6. Hypertrophy of larynx
113
EFFECTS OF TESTOSTERONE (7-12)
7. Increases thickness of the skin and development of acne
8. Increases protein formation and muscle development
9. Increases bone matrix and cause calcium retention
10. Increases basal metabolic rate
11. Increases red blood cell
12. Effect on electrolyte and water balance
114
REGULATION OF HORMONAL CONTROL (MALE)
1. Gonadotrophin-releasing hormone
2. Luteinizing hormone (LH) and Follicular stimulating hormone (FSH)
3. Inhibin
4. Human Chorionic Gonadotrophin
115
* Decrease in male sexual function
| * Hot flushes, suffocation and psychic disorder
MALE CLIMACTERIC
116
* Impotence
* Inability to develop or maintain an erection of sufficient rigidity for satisfactory sexual intercourse
* Trauma to the parasympathetic nerves from prostate surgery, deficient levels of testosterone and some drugs (nicotine, alcohol, antidepressants)
ERECTILE DYSFUNCTION
117
FUNCTIONAL ANATOMY OF FEMALE REPRODUCTIVE TRACT
• Female reproductive system = GONADS (ovaries) + female reproductive TRACT (oviducts, uterus, cervix, vagina, and external genitalia)
118
* Acts via the IP3 mechanism
* Arcuate nuclei of the hypothalamus secrete GnRH into the hypothalamic– hypophysial portal blood.
* stimulates the anterior pituitary to secrete FSH and LH.
GnRH
119
• is initiated by the onset of pulsatile GnRH release from the hypothalamus >> FSH and LH are in turn secreted in pulsatile fashion >> GnRH up regulates its own receptor in the anterior pituitary.
PUBERTY
120
(GnRH and Lactation)
| Ovulation is suppressed as long as lactation continues because PROLACTIN has the following effects:
– Inhibits hypothalamic GnRH secretion
– Inhibits the action of GnRH on the anterior pituitary >> inhibits LH and FSH secretion.
– Antagonizes the actions of LH and FSH on the ovaries.
121
* cAMP mechanism
| * Secreted by the anterior pituitary
FSH AND LH
122
FSH AND LH: Actions
– Steroidogenesis in the ovarian follicle and corpus luteum
– Follicular development beyond the antralstage
– Ovulation
– Luteinization
123
* Stimulates ovulation, formation of corpus luteum, and synthesis of estrogen and progesterone (ovary)
* produce progesterone to maintain the endometrium (from proliferative to secretory phase)
LH (Luteinizing Hormone)
124
* Belong to the same glycoprotein family.
* Each has an α subunit and a β subunit.
* α subunits = identical
* β subunits = Unique
FSH, LH and TSH
125
Phases of Testosterone
* can become Estradiol via CYP 19 (aromatase) - AROMATIZATION
* can become Dihydrotestosterone (DHT) via 5-alpha reductase - REDUCTION
126
Estrogen: Actions (1)
– Has both negative and positive feedback effects on FSH and LH secretion.
– Causes maturation and maintenance of the fallopian tubes, uterus, cervix, and vagina.
– Causes the development of female secondary sex characteristics at puberty.
– Causes the development of the breasts.
– Up-regulates estrogen, LH, and progesterone receptors.
127
Estrogen: Actions (2)
– Causes proliferation and development of ovarian granulosa cells.
– Maintains pregnancy.
– Lowers the uterine threshold to contractile stimuli during pregnancy.
– Stimulates prolactin secretion (but then blocks its action on the breast).
128
Estrogen: Source
– Ovary: estradiol (during reproductive stage)
– Placenta: estriol (during pregnancy)
– Adipose tissue: estrone (via aromatization) (when the ovaries are not functioning/menopause/ovaries are taken out)
129
Estrogen: Potency
estradiol > estriol > estrone
130
Progesterone: Actions
– Has negative feedback effects on FSH and LH secretion during luteal phase.
– Maintains secretory activity of the uterus during the luteal phase.
– Maintains pregnancy.
– Raises the uterine threshold to contractile stimuli during pregnancy.
– Participates in development of the breasts.
131
Facts about Females’ Egg
- 2 million Primary oocytes at birth
- 400,000 follicles at onset of puberty
- Remaining follicles are depleted at a rate of 1000 follicles per month until age 35
- After 35 yo, the rate becomes FASTER
- 400 follicles are normally released during female reproductive life = 400 opportunities for pregnancy (assuming no contraception)
- 99.9% of follicles undergo atresia via apoptosis
132
OOGENESIS:
Fetus >> Puberty >> Fertilization
133
(Oogenesis)
Primary oocytes begin Meiosis I during fetal life and complete meiosis I just before ovulation Meiosis begins but
levels of proteins required for completion of meiosis are too low – oocyte arrests at prophase I. This happens for years, until __
OVULATION
134
(Oogenesis)
What is the event that happens in Prophase I?
- formation of chiasmata
| - crossing over of the genetic material between homologous chromosome
135
(Oogenesis)
As the oocyte grows, it synthesizes enough proteins (CDK 1, cyclin) to complete meiosis but HIGH cAMP levels actively maintain arrest. Therefore: Primary oocyte is __
MEIOTICALLY COMPETENT but ARRESTED
136
(Oogenesis)
A few hours after OVULATION, oocyte completes meiosis I, and Meiosis II is arrested at metaphase II until FERTILIZATION. If fertilization does not occur within 1 day >> secondary oocyte __
DEGENERATES
137
(Oogenesis)
What happens in Metaphase II?
- alignment of the chromosomes at the center
138
• dominant hormone during preovulatory phase
Estrogen
139
• dominant hormone during the post ovulatory phase
Progesterone
140
• the ovary in the follicular phase it produces estrogen. in response to estrogen, what happens in the endometrium?
- it proliferates
| - during the follicular phase of the ovarian phase, it coincides with the proliferative phase of the endometrial cycle
141
Ovarian Cycle and Endometrial Cycle
1. Follicular (Ovary) or Proliferative (Uterus) - increase in estrogen (ovary) will cause the uterus to proliferate
2. Ovulation - triggered by the LH surge; estradiol declines and progesterone increase because of the corpus luteum
3. Luteal (Ovary) or Secretory (Uterus) - increase progesterone will cause the endometrium to increase its nutrition and secretion (glands and vessel)
4. Menstruation
142
• produced by the syncitiotropoblast; hormone that will rescue the corpus luteum from dying
HcG (Human chorionic gonadotrophin)
143
The __ (also called the uterine tubes and the fallopian tubes) are muscular tubes with the distal ends close to the surface of each ovary and the proximal ends traversing the wall of the uterus.
oviducts
144
Oviducts: 4 sections (distal to proximal)
1. Infundibulum + fimbriae
2. ampulla
3. Isthmus
4. intramural or uterine segment - junction where it meets the uterus
145
- where fertilization occurs; most common site for ectopic pregnancy
- Site for sperm storage
- Secrete fluids that provide nutritional support to preimplantation embryo
Ampullary-‐isthmus junction
146
The __ is a single organ that sits in the midline of the pelvic cavity between the bladder and the rectum
uterus
147
Layers of the Uterus:
– Innermost: endometrium (mucosa); reactive to ovarian changes
– Middle: myometrium (three-‐layered, thick muscularis layer)
– Outermost: perimetrium (outer connective tissue and serosa)
148
Parts of the Uterus:
1. FUNDUS, which is the portion that rises superiorly from the entrance of the oviducts
2. the BODY OF THE UTERUS, which makes up most of the uterus
3. the ISTHMUS, a short narrowed part of the body at its inferior end
149
(Uterine Endometrium)
About two thirds of the luminal side of the endometrium is lost during menstruation and is called the __ (also called the stratum functionalis)
functional zone
150
(Uterine Endometrium)
| The basal third of the endometrium that remains after menstruation is called the __ (also called the stratum basale).
basal zone
151
(Uterine Endometrium)
The basal zone is fed by straight arteries that are separate from the __, and it contains all the cell types of the endometrium (i.e., epithelial cells from the remaining tips of glands, stromal cells, and endothelial cells)
spiral arteries
152
The __ is lined by a simple columnar epithelium that secretes cervical mucus in a hormonally responsive manner.
*During the normal menstrual cycle, the conditions of the cervical mucus are ideal for sperm penetration and viability at the time of ovulation.
endocervical canal
153
Cervis: Estrogen and Progesterone
* Estrogen >> stimulates the production of a copious quantity of thin, watery, slightly alkaline mucus that is an ideal environment for sperm.
* Progesterone >> stimulates the production of a scant, viscous, slightly acidic mucus that is hostile to sperm.
154
• The superficial cells of the vaginal epithelium are continually desquamating, and the nature of these cells is influenced by the hormonal environment.
VAGINA
155
Vagina: Estrogen and Progesterone
• Estrogen >> stimulates proliferation of the vaginal epithelium and increases its glycogen content
– The glycogen is metabolized to lactic acid by commensal lactobacilli, thereby maintaining an acidic environment. This inhibits infection by noncommensal bacteria and fungi.
• Progesterone >> increases the desquamation of epithelial cells.
156
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: Bone
– Estrogen is required for closure of the epiphysial plates of long bones in both sexes.
– bone anabolic effect: Estrogen promotes the survival of osteoblasts and apoptosis of osteoclasts, thereby favoring bone formation over resorption)
– calciotropic effect: stimulates intestinal Ca++ absorption.
157
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: Liver
– The overall effect of estradiol-‐17β on the liver is to improve circulating lipoprotein profiles.
– Increases expression of the LDL receptor, thereby increasing clearance of cholesterol-‐rich LDL particles by the liver.
– increases circulating levels of HDL.
158
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: Cardiovascular organs
– Premenopausal women have significantly less cardiovascular disease than men or postmenopausal women do.
– Estrogen promotes vasodilation through increased production of nitric oxide >> relaxes vascular smooth muscle and inhibits platelet activation
159
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: Integument
– Estrogen and progesterone maintain a healthy, smooth skin with normal epidermal and dermal thickness.
– stimulates proliferation and inhibits apoptosis of keratinocytes.
– increase collagen synthesis and inhibit (along with progesterone) the breakdown of collagen by suppressing matrix metalloproteinases.
– increases glycosaminoglycan production and deposition in the dermis and promotes wound healing.
160
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: CNS
– Estrogen is neuroprotective: inhibits neuronal cell death in response to hypoxia or other insults.
– Could be explained by positive effect on angiogenesis
– Progesterone: increase the set point for thermoregulation, thereby elevating body temperature approximately 0.5°F.>> basis for using body temperature measurements to determine whether ovulation has occurred.
– Progesterone is a CNS depressant.
161
EFFECTS OF ESTROGEN AND PROGESTERONE ON NON REPRODUCTIVE TISSUE: Adipose tissue
– Estrogen decreases adipose tissue by decreasing lipoprotein lipase activity and increasing hormone-‐ sensitive lipase (i.e., it has a lipolytic effect).
– Loss of estrogen results in the accumulation of adipose tissue, especially in the abdomen.
162
Loss of progesterone on demise of the corpus luteum of menstruation is the basis for __.
premenstrual dysphoria (premenstrual syndrome [PMS])
163
- A group of symptoms, both physical and behavioral, that occur in the second half of the menstrual cycle and that often interfere with work and personal relationships.
Pre-Menstrual syndrome
164
Pre-Menstrual syndrome (Etiology)
– Hormonal imbalance
| – Alterations in serotonergic neuronal mechanism
165
Pre-Menstrual syndrome: Common Profile of Pts with PMS
– History of maternal PMS
– Low levels of exercise
– Younger age
– Higher parity (more pregnancies)
166
Pre-Menstrual syndrome: Diagnosis
• Symptom diary
– Most useful diagnostic tool
– Symptoms in the last 2 weeks of menstrual cycles (3 months)
• No laboratory tests are available
– Thyroid hypofunction
• Elimination of other diagnoses
167
Pre-Menstrual syndrome: Symptom Diary
* Symptoms MUST be present in at least 3 consecutive cycles
* They MUST be absent in the pre ovulatory phase of menses
* They MUST resolve with onset of menses
* They MUST interfere with normal daily functioning
168
• More severe type of PMS with disabling emotional symptoms
PREMENSTRUAL DYSPHORIC DISORDER
169
Pre-Menstrual syndrome: Treatment
• Diet and Exercise
• Spirinolactone – Fluid retention
• Bromocriptine – Breast tenderness
• SSRI – For those with severe emotional symptoms and PMDD
• TAHBSO (Total Abdominal Hysterectomy with Bilateral Salphingoopherectomy) >> “surgical menopause”
– For severe case of PMS in older women who have completed their families
170
– Permanent cessation of menstruation
– Mean age is 51 years (Filipino 47-‐48 years)
– 12 months of amenorrhea after the final menstrual period
– 3 months of amenorrhea with elevation of gonadotropins (FSH and LH)
Menopause
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– Variable time beginning a few years before and continuing after the event of menopause
– Also known as climacteric
– Median age of onset is 47.5 years
– Median length is about 4 years
Perimenopause
172
Facts (Menopause)
• AGE of menopause is GENETICALLY DETERMINED (unlike the onset of menarche)
• Age of menopause is earlier by 2 years in smokers
• The menopausal age is also NOT RELATED to:
– Number of prior ovulations
– Race
– Socioeconomic status
173
* Depletion of ovarian follicles with degeneration of the granulosa and theca cells while the stromal cells continue to produce androgens, androstenedione, and testosterone
* There is only a slight decrease in circulating levels of the above hormones
Menopause
174
Initial change signaling the onset of menopause
• Decreased in ovarian inhibin production accompanied by increase in pituitary FSH
175
FAT AND MENOPAUSE (Juana Change/Increase Body Fat)
* Less hot flushes and symptoms of estrogen deficiency
* Less likely to develop osteoporosis
* More likely to develop endometrial hyperplasia and adenocarcinoma of endometrium due to increase estrogen level
176
FAT AND MENOPAUSE (Wilma Doesnt/Decrease Body Fat)
* More likely to develop hot flushes and symptoms of estrogen deficiency
* More likely to develop osteoporosis
* Less likely to develop endometrial hyperplasia and adenocarcinoma of endometrium due to increase estrogen level
177
Physiologic effects of Menopause: FAT AND WEIGHT
* Increase in total body weight and total body fat
* Increased waist-‐to-‐hip ratio
* Shift of fat distribution from a gynecoid to android type
* These changes are prevented by ERT
178
Physiologic effects of Menopause: SKIN AND TEETH
* collagen content and skin thickness decrease resulting in generalized thinning, loss of elasticity and wrinkling
* Teeth loss in both the upper jaw
* ERT maintains premenopausal skin thickness and loss of teeth
179
* Pathognomonic Sign of Menopause
* Decrease in circulating level of estrogen alters the hypothalamic thermoregulation
* Most effective treatment: estrogen
HOT FLUSHES/FLASHES
180
Physiologic effects of Menopause: OTHERS
• DECREASED LIBIDO – Improved by IM testosterone
OTHERS:
• Anxiety, depression, irritability, and fatigue
• Headache
• Decreased cognitive functions
181
Physiologic effects of Menopause: Loss of Estrogen and Clinical Significance
* Atrophy of vaginal epithelium —> Senile vaginitis or atrophic vaginitis
* Decreased collagen content of the structures that support the uterus (ligaments), pelvic relaxation —> Uterine descensus or prolapse
182
Physiologic effects of Menopause: Loss of Estrogen and Clinical Significance (2)
* Decreased collagen in the endopelvic fascial tissue in the vaginal wall —> Cystocele, rectocele
* Atrophic changes in the urinary tract lining and loss of ureteral tone —> Urinary urge incontinence, urinary frequency, dysuria, and nocturia
183
LONG TERM EFFECTS OF MENOPAUSE: Cardiovascular Effects
– Risk of cardiovascular disease is increased after menopause
– Estrogen therapy DOES NOT decrease the risk of CV disease
184
Prevention of Bone loss in Postmenopausal Women
* Dietary calcium supplementation (1500mg/day)
* Vitamin D supplementation (1500mg/day)
* Weight-‐bearing exercise should be performed regularly
* Cigarette smoking and alcohol intake should be eliminated
185
Hormone Replacement Therapy: Benefits
– Decreases the vasomotor symptoms (hot flushes, sweating)
– Loss of bone density can be halted with stabilization of trabecular bone formation
– Produces acidic pH of the vagina – decreased incidence of atrophic vaginitis
– Decreases dyspareunia – thickens and cornifies vaginal epithelium
186
- most important source of sensory nerve signals for initiating the male sexual act
– Sensitive sensory end-organ system that transmits into the CNS that special modality of sensation >> sexual sensation
– Slippery massaging action on the glans >> pudendal nerve >> sacral plexus >> the sacral portion of the SC >> undefined areas of the brain
– Impulses may also enter the SC from areas adjacent to the penis (anal epithelium, scrotum, perineal structures)
Glans penis
187
(FEMALE SEXUAL RESPONSE)
| • As is true in the male sexual act, successful performance of the female sexual act depends on __
both psychic stimulation and local sexual stimulation
188
(FEMALE SEXUAL RESPONSE)
| • The glans of the __ is especially sensitive for initiating sexual sensations
clitoris
189
STAGES OF FEMALE SEXUAL ACT
1. Erection - clitoris
2. Lubrication
3. Female orgasm or female climax
4. Resolution
190
* bilateral Bartholin glands, vaginal epithelium, also from male urethra
* Necessary during intercourse to establish a satisfactory massaging sensation rather than an irritative sensation, which may be provoked by a dry vagina
* A massaging sensation constitutes the optimal stimulus for evoking the appropriate reflexes that culminate in both the male and female climaxes
Lubrication
191
When local sexual stimulation reaches maximum intensity, and especially when the local sensations are supported by appropriate psychic conditioning signals from the cerebrum, reflexes are initiated that cause the __
female orgasm, or female climax
192
Physiologic significance of orgasm (Female)
* Reflexes increase uterine and fallopian tube motility during the orgasm
* In many lower animals, copulation causes oxytocin secretion
193
FEMALE REPRODUCTIVE UNIT
• Single ovarian follicle
– One germ cell (oocyte)
– Surrounded by endocrine cells
• About every 28 days, gonadotropic hormones from the anterior pituitary cause about 8 to 12 new follicles to begin to grow in the ovaries
• One of these follicles finally becomes "mature" and ovulates on the 14th day of the cycle
194
* Normally takes place in the ampulla of one of the fallopian tubes soon after both the sperm and the ovum enter the ampulla
* Before a sperm can enter the ovum, it must first penetrate the multiple layers of granulosa cells attached to the outside of the ovum (the corona radiata) and then bind to and penetrate the zona pellucida surrounding the ovum
FERTILIZATION OF THE OVUM
195
Transport of fertilized ovum in the fallopian tube
* Before implantation, the blastocyst obtains its nutrition from the uterine endometrial secretions >> uterine milk
* Implantation of the blastocyst, invasion of cyto-and syncitio-tropho- Blasts >> formation of the placental hypothalamic-pitutiary axis
196
Blastocyst
- reaches the uterus (day 4-5)
| - implants (days 5-7)
197
Early nutrition of the embryo
* When conceptusimplants in the endometrium, (+) continued secretion of progesterone >> endometrial cell swelling and storage of more nutrients
* These cells are now called decidual cells,and the total mass of cells is called the decidua
* Trophoblast cells invade the decidua–only means of nutrition during 1st week
* Embryo continues to obtain at least some of its nutrition in this way for up to 8 weeks, although the placenta also begins to provide nutrition after about the 16th day beyond fertilization (a little more than 1 week after implantation)
198
What happen to the spiral artery during pregnancy?
* modify the spiral artery in such a way that it will become high-low-low resistant to increase blood supply
* replacement of smooth muscle (lumen will become more dilated)
* invasion of uterine cell
199
FUNCTIONS OF THE PLACENTA
1. Fetal gut in supplying nutrients
2. Fetal lung in exchanging O2 and CO2
3. The fetal kidney in regulating fluid volumes and disposing of waste metabolites
4. Endocrine gland synthesizing many steroids and protein hormones that affect both maternal and fetal metabolism
200
(HORMONAL FACTORS IN PREGNANCY)
| In pregnancy, the placenta forms especially large quantities of the ff:
– Human chorionic gonadotropin
– Estrogens
– Progesterone
– Human chorionic somatomammotropin also known as human placental lactogen in lower forms of mammals
201
* Secreted by the syncytial trophoblast cells into the fluids of the mother
* First appears in maternal blood 7-9 days post- fertilization
* Peaks at 8-10 weeks (100,000 mIU/ml)
* Gradually falls to plateau at 18-22 weeks
* also known as the pregnancy hormone
* responsible for morning sickness
HUMAN CHORIONIC GONADOTROPIC (hcG)
202
• Prevents involution of the corpus luteum at the end of the monthly female sexual cycle
– If the CL is removed before approximately the 7th week, spontaneous abortion almost always occurs, sometimes even up to the 12th week
– Placenta secretes sufficient quantities of progesterone and estrogens to maintain pregnancy for the remainder of the gestation period
– CL involutes slowly after the 13th to 17th week of gestation
• Production of testicular estrogen in male fetuses
HUMAN CHORIONIC GONADOTROPIC (hcG)
203
* Enlargement of the mother's uterus
* Enlargement of the mother's breasts and growth of the breast ductal structure
* Enlargement of the mother's female external genitalia
* Relax the pelvic ligaments of the mother, so the sacroiliac joints become relatively limber and the symphysis pubis becomes elastic
ESTROGENS
204
* Causes decidual cells to develop in the uterine endometrium >> nutrition of the early embryo
* Decreases the contractility of the pregnant uterus
* Increases the secretions of the mother's fallopian tubes and uterus to provide appropriate nutritive matter for the developing morula
* Helps the estrogen prepare the mother's breasts for lactation
PROGESTERONE
205
* Secreted by the placenta at about 5th week
* Secretion increases progressively throughout the remainder of pregnancy in direct proportion to the weight of the placenta
* In lower animals, partial development of the animal's breasts and in some instances causes lactation >> formerly known as human placental lactogen
* Weak actions similar to those of growth hormone
* Causes decreased insulin sensitivity and decreased utilization of glucose in the mother >> making larger quantities of glucose available to the fetus.
HUMAN CHORIONIC SOMATOMAMMOTROPIN
206
Maternal adaptations to pregnancy
* Increased basal metabolic rate by about 15% during the latter half of pregnancy
* Increased cardiac output –increased Blood Flow to placenta;
* Increased minute ventilation –progestrone increased respiratory center’s sensitivity to CO2
* Increased Renal Blood Flow and GFR
207
PHYSIOLOGIC WEIGHT GAIN
1st trimester – 2 lbs
2nd trimester – 11 lbs
3rd trimester – 11 lbs
208
4 PERIODS OF INCREASE CARDIAC OUTPUT
* On 28th week – highest peak of cardiac load
* During labor – increased flow to heart from uterine squeezing, increased HR due to labor pains
* Immediately after labor – due to increased venous return
* During 1st week of puerperium – mobilization of interstitium
209
Maternal adaptations to pregnancy (No Change)
No Change in:
- Systolic Blood Pressure
- Lung Compliance
210
Maternal adaptations to pregnancy (Increase)
Increase in:
- Pulse Pressure
- Tidal volume
- Gastric Emptying Time
- Creatine clearance
- Renal Blood flow
- Blood coagulation factors
- Cortisol and aldosterone
211
Maternal adaptations to pregnancy (Decrease)
Decrease in:
- Total Peripheral Resistance
- Total Pulmonary Resistance
- Serum creatine
- Hematocrit
- Platelet count
- Intraocular Pressure (IOP)
- Potassium and Sodium
212
• Birth of the baby
• Toward the end of pregnancy, uterus becomes progressively more excitable strong rhythmical contractions that the baby is expelled
• Intense contractions responsible for parturition due to:
– Progressive hormonal changes that cause increased excitability of the uterine musculature
– Progressive mechanical changes
PARTURITION
213
Phases or Parturition
Phase O (Quiescence) - Progesterone; prelude to parturation; from implantation to few weeks before delivery
Phase 1 (Activation) - Estrogen; Preparation for labor; occurs in the last 6-8 weeks of pregnanct
Phase 2 (Stimulation) - Oxytocin; Process of Labor
Phase 3 (Involution) - Oxytocin; Parturient recovery
214
OXYTOCIN AND UTERINE CONTRACTIONS
- Uterine muscle increases oxytocin receptors >> increased responsiveness
- Increased rate of secretion at the time of labor
- Labor is prolonged in hypophysectomized animals
- Irritation or stretching of the uterine cervix, as occurs during labor, can cause a neurogenic reflex through the paraventricular and supraoptic nuclei of the hypothalamus signals neurohypophysis to increase secretion
215
“Positive feedback” theory of parturition
- squeezing of the uterus on the baby's breech >> push the uterus downward >> stretch out the cervix >> stimulation of more vigorous contraction
- oxytocin from the uterus and mother's pituitary >> stimulate the uterus to contract and also stimulate placenta to make Progesterone >> stimulation of vigorous contraction
216
“Positive feedback” theory of parturition (2)
1. Baby's head stretches the cervix
2. Cervical stretch excites fundic contraction
3. Fundic contraction pushes the baby down and stretches the cervix more
4. Cycle repeats over and over again
217
- characterized by regular uterine contraction that lead to cervical effacement and dilatation
Labor
218
Stages of Labor
```
Stage 1: Latent Phase (Effacement)
Active Phase (Activation)
```
Stage 2: Descent
Stage 3: Expulsion
219
(Lactation)
- begins at puberty due to estrogen stimulation >> increased during pregnancy due to estrogen, progesterone and prolactin
Breast development
220
(Lactation)
| - secreted by anterior pituitary, starting from 5th wk of pregnancy until birth, then cycles
Prolactin
221
(Lactation)
| - 1st milk , contains same proteins and lactose as milk, but no fat
Colostrum
222
• Initiated by precipitous drop in estrogen and progesterone after delivery
• Prolactin surges each time mother nurses baby due to nerve impulses from nipples to hypothalamus
–without nursing stimulation, no prolactinsurge, and loss of milk production
• inhibits FSH, LH and thus lactation interferes with reproductive function
Lactation
223
When not nursing, hypothalamus produces __
prolactin-inhibitory hormone
224
• ACTION
–Milk EJECTION
–Uterine Contraction (basis for Nipple Stimulation)
• Used to induced labor and reduce postpartum bleeding
• STIMULI
–Sucking
–Orgasm
–Dilation of cervix
• In males: for contraction of vas deferens during ejaculation
Oxytocin
