12) Sex Differentiation Flashcards
(174 cards)
1
Q
What is the common primordium for external genitalia?
A
Urogenital sinus
2
Q
What does the Mullerian duct become? Which sex possesses the Mullerian duct?
A
- Females
- Oviduct, uterus, upper vagina
3
Q
What does the urogenital sinus become in females?
A
Clitoris, vulva
4
Q
What does the urogenital sinus become in males?
A
Penis, scrotum
5
Q
What does the Wolffian duct become? Which sex possesses the Wolffian duct?
A
- Males
- Epididymis, vas deferens, seminal vesicle
6
Q
The removal of undifferentiated testes from male rabbit embryos produced what type of reproductive tract and genitalia?
A
- Female reproductive tract
- Female genitalia
7
Q
What type of reproductive tract and genitalia is produced from gonadectomised female embryos?
A
Female features
8
Q
The testes are (necessary/not necessary) for male sexual differentiation.
A
necessary
9
Q
The ovaries are (necessary/not necessary) for female sexual differentiation.
A
not necessary
10
Q
The development of male features is hormone (dependent/independent).
A
dependent
11
Q
The development of female features is hormone (dependent/independent).
A
independent
12
Q
Is the development into a male or female the default pathway?
A
Female
13
Q
What are the three pre-requisites for normal sex differentiation?
A
1) Normal intact chromosome complement
2) Fully functioning sex determination genes
3) Intact steroidogenic pathway and receptors
14
Q
Why is sexual differentiation required in males?
A
Provision of sperm
15
Q
Why is sexual differentiation required in females?
A
- Provision of eggs
- Internal fertilization
- Pregnancy
- Lactation
16
Q
How are males and females different in terms of their chromosomes?
A
- Males: XY
- Females: XX
17
Q
True or False: the presence of the Y chromosome always produces a male phenotype.
A
True
18
Q
What is Klinefelter syndrome? What are symptoms?
A
- Two or more X chromosomes in males
- Sterility and small testicles
19
Q
What is Turner syndrome? What are symptoms?
A
- A female is partly or completely missing an X chromosome (XO)
- Short stature, loss of ovarian function
20
Q
Normally, chromosomes pair and cross-over at which sections?
A
They cross-over along ALL their length
21
Q
How do X and Y chromosomes pair?
A
Y pairs with X only at one end (pairing region)
22
Q
How do X and Y chromosomes cross-over?
A
There are RARELY crossing-over events between X and Y
23
Q
What does the sry gene stand for?
A
Sex-determining region of the Y chromosome
24
Q
Is the SRY gene retained in the pairing or non-pairing region?
A
In the non-pairing region of the Y chromosome
25
What occurs when the SRY gene is mis-paired, and transferred to the X chromosome?
- Sperm produces an X chromosome with the SRY gene
| - Fertilization by the sperm would produce an XX male
26
What occurs if the SRY gene is deleted or mutated in the Y chromosome?
Produces an XY female
27
23/24 of the mutations causing an XY female lie in which region?
DNA-binding domain (HMG box) of the SRY gene
28
An amino acid region of the SRY gene shows homology to a motif within the _______ proteins, which possesses DNA-binding activity.
high mobility group (HMG)
29
Is DAX1 contained on the X or Y chromosome? What is its function?
- X chromosome
| - Inhibits testicular development
30
What genes does the SRY gene inhibit?
- WNT4
| - DAX1
31
The expression of SRY leads to the expression of other genes, leading to ____.
AMH
32
What is AMH? What produces AMH?
- Anti-mullerian hormone (Mullerian-inhibiting substance)
| - Produced by Sertoli cells
33
The differentiation of the gonad by what genes results in Sertoli cells producing AMH, and Leydig cells producing testosterone?
- SRY
- SOX9
- SOX3
34
How does testosterone affect the Wolffian duct?
Positive effect on the development of the Wolffian duct
35
Which component allows for the development of male external genitalia?
Dihydroxytestosterone (DHT) produced from testosterone
36
Which component allows for the development of female external genitalia?
The lack of DHT from the lack of testosterone
37
What is responsible for testicular descent?
Testicular hormones
38
What guides testicular descent?
Gubernaculum
39
What hormone allows for trans-abdominal descent of the testes?
AMH
40
What allows for inguino-scrotal descent of the testes to the scrotal position?
Testosterone
41
How does the gubernaculum guide testicular descent?
- The gubernaculum swells, providing traction to the testes to pull them through the inguinal canal
- The testes are pulled to the outside of the body
- The gubernaculum shrinks and the inguinal canal seals
42
What are the effects of defects in testosterone synthesis or actions? (3)
1) Phenotypic female (XY)
2) No ovaries (testes, but infertile)
3) Blind-ending vagina
43
What is the cause of androgen-insensitivity syndrome? What are symptoms?
- A lack of androgen receptors
| - Lack of epididymis, vas deferences, presence of female external genitalia
44
What are possible causes for defects in testosterone synthesis or action?
- StAR protein deficiency
- Leydig cell hypoplasia
- Deficiency in 17-hydroxylase, 17-lyase
45
Do individuals with androgen-insensitivity syndrome possess testes?
- Yes, but they are contained within the abnominal cavity (cryptorchidism)
- The gubernaculum cannot shrink, and the testes can't be pulled through the inguinal canal
46
What is the treatment for androgen-insensitivity syndrome?
- Surgery to correct the ambiguous genitalia
| - Gonadectomy post-puberty
47
How does the quantity of aromatase differ in individuals with androgen-insensitivity syndrome?
High levels of aromatase
48
What is the effect of congenital adrenal hyperplasia?
- Hyperplasia of the adrenal glands before birth, causing excessive androgen production
- Masculinization of the external genitalia at birth
49
What is the most common defect in CAH?
21-hydroxylase deficiency
50
What are the effects of a deficiency in 21-hydroxylase? (3)
1) Low cortisol and aldosterone production
2) Reduced negative feedback onto the hypothalamic/pituitary axis
3) Increased androgen production
51
What allows for the sexual differentiation of the brain?
- Testosterone is converted to estrogen by aromatase
| - Estrogen binding to its receptor in the brain causes sexual differentiation
52
When does sexual differentiation of the brain occur? How does it vary among species?
- Occurs during a "critical time period" during development
| - The timing is variable by species
53
When does sexual differentiation of the brain occur in primates?
3 to 6 months pre-natally
54
What is the effect of gonadal steroids on the "indifferent" brain?
Masculinization
55
How may sexual differentiation of the brain affect structure and function?
- Affects the propensity of psychiatric diseases
| - Differences in brain activity patterns (apparent over wide range of cultures)
56
What is the effect of CAH on child play patterns? Why?
- Tendency towards male play patterns
| - Exposure to androgens in utero
57
Which center controls LH and FSH in males post-puberty?
Tonic center
58
Do males possess a surge center?
No, the surge center is defeminized and does not develop
59
Does testosterone freely enter the brain? Does estrogen?
- Testosterone: yes (converted to estradiol)
| - Estradiol: no
60
What occurs to estradiol produced by the fetal ovary?
Binds to alpha-fetoprotein
61
Which center controls LH and FSH in females post-puberty?
Surge center AND tonic center
62
What are the two functions of the gonads?
1) Gametogenesis
| 2) Hormonogenesis
63
What are the three functional outcomes of hormonogenesis?
1) Electrolyte homeostasis
2) Fuel and protein metabolism
3) Adiposity and muscle mass
64
The sex determination of the fetus requires the hypothalamic-pituitary-gonadal axis in which sex?
- Required in males
| - Not required in females
65
Sexual changes in puberty requires the hypothalamic-pituitary-gonadal axis in which sex?
Important in BOTH sexes
66
What is required for reproduction in females?
Sex hormones during pregnancy and parturition
67
Does menopause or andropause require the hypothalamic-pituitary-gonadal axis?
Important in BOTH sexes
68
How does testosterone vary during the fetal period? What is the function?
- Rise in testosterone
| - Associated with sexual differentiation
69
How does testosterone vary during the neonatal period? What is the function?
- Rise in testosterone
| - Function is unknown
70
How does testosterone vary during the pre-pubertal period?
Gonads are dormant in both sexes
71
How does adrenal androgen expression vary in the life cycle?
- On average, androgen expression increases until age 20, and decreases afterwards
- Transient increase in androgens during puberty
72
How do male plasma hormones vary through puberty?
Increase in FSH and LH, associated with an increase in testosterone
73
How do female plasma hormones vary through puberty?
Increase in FSH and LH, associated with an increase in estradiol
74
Define puberty.
- The physiological, morphological, and behavioural changes that occur in the growing animal
- Development of gonads/brain/phenotype as they change from adolescent to adult
75
What characterizes the onset of puberty in females?
First menstrual cycle (menarche)
76
What characterizes the onset of puberty in males?
First ejaculation (semarche)
77
How are menarche and semarche associated with fertility in females and males?
Both of these events do NOT signify fertility
78
What is the pulsatile pattern of GnRH release in adulthood? What is it during puberty?
- Adult: 90 minutes
| - Puberty: diurnal
79
The ________ release of GnRH regulates sexual development.
pulsatile
80
What evidence suggests that the pulsatile release of GnRH regulates sexual development?
1) FSH and LH are present in the pituitary, and GnRH in the hypothalamus, before the onset of puberty (but they are not released)
2) Gonads of children can be stimulated by pulsatile administration of GnRH
81
Describe the release of GnRH prior to puberty.
GnRH neurons in both the tonic and surge centers of the hypothalamus release low amplitude and frequency pulses of GnRH
82
Describe the release of GnRH after puberty in the female. What do the tonic and surge centers control?
- Tonic center controls basal levels of GnRH
| - Surge center controls the pre-ovulatory surge of GnRH
83
Which sex possesses a surge center?
Only the female
84
How does GnRH secretion vary at the onset of puberty?
Rise in GnRH (both in amplitude and frequency of the pulses)
85
What causes the increase in pulses of GnRH secreted from the hypothalamus?
Decreased sensitivity of the TONIC CENTER to negative feedback from gonadal steroids
86
How does the sensitivity of the tonic center vary during puberty?
Decreased sensitivity to negative feedback from gonadal steroids
87
How does the sensitivity of the surge center vary during puberty?
There is no alteration in surge sensitivity
88
If there is no alteration in the surge center's sensitivity, how is surge release stimulated after puberty?
Before puberty, estrogen levels are not high enough to stimulate surge release
89
What occurs as a result of an increase in GnRH during puberty?
- Increase in pulses of LH and FSH
| - Increase in steroid levels to support spermatogenesis and folliculogenesis
90
What substance regulates the pulsatile secretion of GnRH from GnRH neurons?
Kisspeptin (KISS1)
91
Kisspeptin is secreted from neurons whose cell bodies are located in which nuclei of the hypothalamus? (2)
- Anteroventral periventricular (AVPV) nuclei
| - Arcuate (ARC) nuclei
92
Kisspeptin contributes to a positive feedback circuit alongside which substances?
- Estradiol
| - GnRH
93
Describe the estradiol-kisspeptin-GnRH positive feedback circuit.
- Rising levels of estradiol act to increase kisspeptin
| - Kisspeptin amplifies GnRH neuron activity
94
How do the levels of kisspeptin vary after the onset of puberty in females?
- Fluctuate with the cyclical levels of estradiol
| - To drive the generation of the pre-ovulatory GnRH/LH surge
95
The (age/body weight) of puberty in girls has been changing, but the (age/body weight) has not.
age
| body weight
96
What is the critical body weight to allow for the activation of the hypothalamic-pituitary-gonadal axis?
47 kilograms
97
How has the onset of puberty varied in the past century? Why?
- The onset of puberty is becoming earlier
| - Better nutrition and health allow girls to reach 47 kg faster
98
What is the size of GnRH?
Decapeptide (10 amino acids)
99
What is co-synthesized with GnRH in pre-pro GnRH?
GnRH-associated peptide (GAP)
100
Which signal transduction mechanism allows for the stimulation of gonadotrophs by GnRH?
- GPCR (PLC)
| - Increase in calcium and PKC increases FSH/LH secretion
101
How does a long-acting GnRH analog affect the pituitary secretion of LH?
Desensitization of the pituitary, due to the lack of pulsatility
102
How does exogenous GnRH (when GnRH is absent) affect the pituitary secretion of LH?
Little or no gonadotrophin response
103
GnRH is released alongside ___.
GAP
104
Where do axons of GnRH terminate?
Hypophyseal portal capillaries
105
What other tissues synthesize GnRH, apart from the hypothalamus? What is its function?
- Placenta
- Gonads
- Breast
- Lymphocytes
- Pituitary
- The function is unknown
106
What is the common subunit of FSH and LH? The subunit is also shared with which hormones?
- alpha subunit
| - TSH and hCG
107
What differentiates LH and FSH?
The B-subunit
108
What creates different isoforms of LH and FSH with slightly different biological properties?
- Changes in glycosylation that may occur in circulation
| - LH and FSH are glycoproteins
109
Which signal transduction mechanism does FSH utilize?
- GPCR
| - Adenylate cyclase
110
Which signal transduction mechanisms does LH utilize?
- GPCR
| - Adenylate cyclase and PLC
111
What are the target tissues of LH in the male and female?
- Male: Leydig cells
| - Female: Thecal cells
112
What are the target tissues of FSH in the male and female?
- Male: Sertoli cells
| - Female: Granulosa cells
113
The actions of LH and FSH are the same as which hormone? What is its target organ?
ACTH on the adrenal cortex
114
What are the events of LH and FSH that are the same as ACTH on adrenal cortex cells?
1) Increase in intracellular cholesterol
2) Transport of cholesterol by StAR
3) Conversion to pregnenolone
115
Which hormone(s) is/are steroidogenic in the testes? Which cells does it act upon?
- LH
| - Leydig cells
116
Which hormone(s) is/are steroidogenic in the ovaries? Which cells does it act upon?
- LH and FSH
| - Several cell types (thecal cells and granulosa cells)
117
What are the three important cell types in spermatogenesis?
- Spermatogonia
- Sertoli cells
- Leydig cells
118
Where are Sertoli cells located with respect to the seminiferous tubules? Where are Leydig cells located?
- Sertoli cells are inside the seminiferous tubules
| - Leydig cells are outside the seminiferous tubules
119
What is the significance of the location of Sertoli cells?
- Located inside the seminiferous tubules
- Isolated from the immune system
- Responsible for maintaining the environment of spermatogonia to produce sperm cells
120
What are the most important androgens secreted by the testes?
- DHEA
| - Testosterone
121
The contribution from the adrenal gland to the synthesis of androgens is less than _%.
5
122
What are androgens synthesized from the testes bound to in circulation? Why must they be bound?
- Albumin
- Sex-hormone-binding globulin (SHBG)
- Lipophiles must be bound in circulation
123
Cells that do not contain active testosterone must convert testosterone to what?
Dihydroxytestosterone (DHT)
124
Which type of testosterone may be converted to estradiol by target tissues? Which type cannot?
- Testosterone can be converted
| - DHT cannot be converted
125
Which cells synthesize testosterone?
Leydig cells
126
What is the intermediate compound between DHEA and testosterone?
Androstenedione
127
What enzyme converts testosterone to estradiol?
Aromatase
128
What enzyme converts testosterone to DHT?
5a-reductase
129
When do occasional pulses of LH and FSH occur in young children?
Mainly nocturnal pulses
130
If children produce occasional pulses of LH and FSH, why aren't they able to produce secondary sex characteristics at puberty?
The production of steroid hormones is not high enough
131
What occurs to spermatogonia during puberty?
- Mitotic proliferation
| - They begin to divide, and continue to do so throughout the adult life
132
Describe the developmental steps to the production of spermatids.
1) Spermatogonia differentiates into a primary spermatocyte
2) Primary spermatocyte undergoes meiosis I to become a secondary spermatocyte
3) Secondary spermatocyte undergoes meiosis II to become a spermatid
133
What is the function of Sertoli cells in spermatogenesis?
- Secretion of steroidal mitotic factor and androgen binding protein
- Concentration of testosterone in the seminiferous tubules
134
Where does sperm further mature?
In the seminiferous tubules and epididymis
135
What is the most frequent cancer in men in industrialized countries?
Prostate cancer
136
What metabolite is elevated in prostate cancer?
PSA
137
What is the function of the prostate in terms of sperm development?
- Prostate excretes a serine protease (prostate specific antigen)
- PSA inactivates the sperm motility inhibitor
138
What occurs to the prostate in later life in dogs and humans?
- Prostate encircles the urethra and enlarges during later life
- Eventually, restricts urine flow
139
What is the surgical treatment for issues with the prostate in old age?
Enlarge the urethra and remove part of the prostate
140
What is the medical treatment for issues with the prostate in old age?
- Treat with anti-androgens
| - Suppression of testosterone suppresses the enlargement of the prostate
141
Why is the treatment of anti-androgens effective in older men with an enlarged prostate?
- Prostate is more responsive to testosterone in old age
| - Due to an increased number of receptors
142
What allows for the detection of prostate cancer?
Rectal palpation and/or PSA
143
Which hormones act directly to control testicular function? Which hormone acts indirectly?
- FSH and testosterone act directly
| - LH acts indirectly by stimulating the Leydig cells to produce testosterone
144
What is the function of androgen binding protein?
- Bioconcentrates testosterone in the seminiferous tubules and epididymis
- Promotes spermatogenesis and maturation
145
___ facilitates the last stages of spermatid maturation.
FSH
146
____ and _________ are required for the maturation of spermatids to spermatozoa.
LH and testosterone
147
__ is not required for the gametogenesis in the male. _____________ may be used instead.
LH
| exogenous testosterone
148
What are current methods for male contraceptives?
- Vasectomy
| - Condoms
149
What are characteristics of an ideal male contraceptive?
- Rapidly effective and fully reversible
- Does not interfere with other testosterone-dependent processes
- Has no short or long-term side effects
- Has no impact on eventual offspring
- Be acceptable for both partners
150
Where does spermatogenesis occur?
Seminiferous tubules in the testes
151
What is the overall mechanism of spermatogenesis?
Diploid spermatogonia undergo a series of divisions and differentiation to form haploid spermatozoa
152
Where are haploid spermatozoa mainly stored?
Epididymis
153
How long is the spermatogenesis process?
60 to 70 days
154
Which androgen is involved in spermatogenesis? Where is it produced and what does it act on?
- Testosterone from Leydig cells
| - Acts on Sertoli cells
155
What is the function of FSH in spermatogenesis?
- Acts on Sertoli cells to increase ABP in testes
| - Allows a high concentration of testosterone in the seminiferous tubule
156
What are most male hormonal contraceptions based on?
The usage of exogenous androgen and progestogen to suppress LH and FSH by increasing negative feedback
157
What occurs with the depletion of LH and FSH in males?
- Depletion of intra-testicular testosterone and ABP
- Decreased testosterone in the seminiferous tubules
- Spermatogenesis is inhibited
158
What must male contraceptives provide to maintain libido and secondary sex characteristics?
Peripheral testosterone
159
What occurs after stopping male hormonal contraception?
Gradual recovery of spermatogenesis over months
160
What are side effects of male hormonal contraception?
- Acne
| - Higher levels of testosterone
161
Male hormonal contraception have similar side effects to what?
Drug abuse of anabolic steroids by athletes
162
What are other male hormonal treatments that may be used?
- GnRH antagonists and testosterone
- FSH antagonists
- Inhibin agonists
163
How often is GnRH released?
Pulses occur every 90 minutes
164
What is the regulator of negative feedback of GnRH, LH, and FSH?
- GnRH: testosterone
- LH: testosterone
- FSH: inhibin
165
What is inhibin produced by?
Sertoli cells in response to FSH
166
What is the function of inhibin?
Selective reduction of the amount of FSH produced
167
How does the function of activins differ from inhibins?
- Activins stimulate FSH release
| - Inhibins inhibit FSH release
168
What chains produce inhibins? What chains produce activins?
- Inhibin: alpha + beta
- Activin: beta + beta
- Alpha and beta chains are encoded by different genes
169
Which sex utilizes both inhibin A and inhibin B? Which sex utilizes only inhibin B?
- Women: inhibin A and inhibin B
| - Men: inhibin B
170
Are estrogen and progesterone responsible for a stimulatory or inhibitory effect in the female?
They are responsible for both, depending on the stage of the cycle
171
A defect in spermatogenesis is the cause in about __% of cases of lack of conception.
30
172
What are causes of male infertility?
- Lack of LH or FSH secretion
- Overproduction of prolactin
- Primary failure of testes (cryptorchordisn)
- Reduced sperm motility
- Autoimmune response to sperm
- Chromosomal abnormality
173
What is the result of an overproduction of prolactin in males?
Testicular involution
174
Which chromosomal abnormality may result in male infertility? What is the karyotype?
- Klinefelter syndrome
| - 47XXY
