01- Reproduction Flashcards
What are chromosomes and what is their main function?
Nuclear structures containing a linear thread of DNA
They transmit genetic informaton
What is a karyotype?
A full set of chromosomes in a cell
What are two characteristics of the Y chromosme?
It is small and acrocentric (centromere is located at one end)
What does mitosis result in?
The formation of two identical daughter cells with the same number of chromosomes and DNA content
What are the five phases of mitosis?
Prophase, prometaphase, metaphase, anaphase, and telophase
Where does meiosis occur?
Germ cells such as spermatogonia or oogonia
What does meiosis result in?
Four haploid daughter cells that do not carry the same genetic information
What occurs in cell division 1 of meiosis?
Recombination and the reduction to a haploid number of chromosomes
What occurs in cell division 2 of meiosis?
Chromatids of each chromosome are seperated
What is the product of spermatogenesis?
One spermatogonium yields four spermatids
What is the result of oogenesis?
One oogonium yields one mature oocyte and two polar bodies
What determines the genotypic sex of an offspring?
The sex chromosomes from the parents
What does genotypic sex influence?
The gonadal sex
What does the gonadal sex determine?
The phenotypic sex, which is fully established at puberty
What is an epigenetic modification?
A change in phenotype without a change in genotype
What are the two main epigenetic modifications?
DNA methylation and histone modification
What does epigenomes direct in a fetus?
Development of undifferentiated stem cells at the right time and sequence
What occurs in the undifferentiated gonad during testis development?
The testis develop from the medulla and the cortex regresses
What occurs in the undifferentiated gonad during ovary development?
The ovary develops from the cortex while the medulla regresses
When is the male sex established and how?
When the primary sex cords differentiate into seminiferous tubules under the influence of the testis-determining factor
Where is testis-determining factor located?
On the short arm of the Y chromosome
How is an XX male formed and what are the consequences?
TDF is translocated due to abnormal exchange of genetic material, so is present on the X chromosome.
They will be sterile, have small testes, and display feminine characteristics
What is an example of gonadal dysgenesis due to abnormal gonadal differentiation and what are the characteristics?
Turner Syndrome (XO) Gonads appear as a streak on the pelvic sidewall, short stature, primary amenorrhea, sexual infantilism, and other congenital abnormalities
What can SRY-gene anomaly cause and what are two examples?
Discordance between genotype and gonadal phenotype
Hermaphrodites that have no Y chromosome but have testis and pseudohermaphrodites which have one type of gonadal tissue but morphological characteristics of both sexes
What happens to the indifferent duct system in male development?
The paramesonephric (Mullerian) duct degenerates and the mesonephric (Wolffian) duct develops the vas deferens, seminiferous tubules, and ejaculatory duct
What happens to the indifferent duct system in female development?
The mesonephric (Wolffian) duct degenerates and the paramesonephric (Mullerian) duct develops into the oviducts (fallopian tubes), uterus, and upper third of the vagina
What happens if the testes are removed before differentiation?
Testosterone and anti-mullerian hormone are not present, so the ducts develop in the female pattern (mullerian develops and wolffian degenerates)
What happens if the ovaries are removed before differentiation?
Ducts develop in the regular female pattern
What do AMH and testosterone do during duct development?
AMH is responsible for the regression of the mullerian duct and testosterone is responsible for the development of the wolffian duct
Which enzyme is necessary to convert testosterone into dihydrotestosterone?
5alpha-reductase
What is the critical period for testicular development?
9 weeks of gestation
What is testosterone necessary for in male development?
The wolffian phase of male sexual differentiation and internal male duct development
What is dihydrotestosterone necessary for in male development?
Virilization of the urogenital sinus, the prostate, the penile urethra, and the external genitalia during embryogenesis. Secondary sexual characteristic development during puberty also requires this.
Which cells produce AMH?
Sertoli cells
Which cells begin to produce testosterone after AMH production has begun?
Leydig cells
What occurs if there is lack of androgen production or functioning androgen receptors?
Sexual ambiguity
What do sertoli cells produce?
Androgen binding protein
What occurs to male development if testosterone is absent after male selection has occurred?
The wolffian system remains rudimentary and normal male internal ductal development does not occur
What happens is 5alpha-reductase or DHT are absent?
There is impaired virilization of the external genitalia
Deficiencies in what cause virilization in females and ambiguous genitalia as a result of hypersecretion of adrenal androgens?
21alpha-hydroxylase, 11beta-hydroxylase, and 3beta-hydroxysteroid dehydrogenase
What does a 21alpha-hydroxylase deficiency cause both chemically and phenotypically?
The reduction in the conversion of progesterone to 11-deoxycorticosterone (instead forms aldosterone)
Also reduces the conversion of 17alpha-hydroxyprogesterone to 11-deoxycortisol
This causes the clitoris to be enlarged and labioscrotal folds to be fused
What occurs in feminization syndrome?
The testes of a genetic male fail to descend due to 5alpha-reductase deficiency and complete androgen resistance
What occurs in male pseudohermaphroditism?
There is ambiguous external genitalia or female appearing genitalia due to a defect in the mechanisms by which androgens act on target tissues
What occurs in 5alpha-reductase deficiency?
There is ambiguous genitalia in males due to the lack of DHT
How does the affinity of DHT and testosterone compare?
DHT binds with 100 fold greater affinity
What is AMH?
A homodimer of two monomeric glycoprotein subunits that are linked y disulfide bonds
What is the difference between endocrine, paracrine, and autocrine?
Endocrine acts on distant tissues
Paracrine acts on neighbouring cells of the same tissue
Autocrine acts on the same cell that released the molecule
What are the two primary function of gonads?
Producing gametes and sex hormones
What does the prostate grand secrete and how much of the semen does it make up?
A slightly acidic milky fluid that makes up 50-75% of the semen
What pH range is semen in and why?
It is alkaline to neutralize the acidic vaginal conditions. This allows the prolonged life of spermatozoa
Where does sperm maturation occur?
Epididymis
What are the functions of the hypothalamus?
Secretion of regulatory hormones for the pituitary gland, production of vasopressin and oxytocin, and control of sympathetic output to the adrenal medulla
What does the male hypothalamic-pituitary-gonadal axis control?
Production of male gametes and androgen biosynthesis
Which two gonadotropins are released due to stimulation via gonadotropin-releasing hormone?
Luteinizing hormone and follicle-stimulating hormone
Where is gonadotropin-releasing hormone synthesized?
Small-bodied peptidergic neurons in the arcuate nucleus and preoptic area
Where does LH bind in men and what does it do?
Leydig cells
Stimulates the transcription of proteins involved in the biosynthesis of testosterone
Where does FSH bind in men and what does it do?
Sertoli cells
Stimulates gene transcription for androgen-binding protein, aromatase, growth factors, and inhibin
Where does negative feedback occur in the hypothalamic-pituitary-testicular axis?
Testosterone inhibits the release of GnRH and LH
Inhibin inhibits the release of FSH
What family of hormones are LH, FSH, hCG, and TSH?
Glycoprotein hormones
What is different about the four glycoprotein hormones and what does this allow?
The beta subunits, which confers specific functional and immunological characteristics
Where is hCG secreted?
Mainly by the placenta, and in small amounts in the testes and pituitary gland
What is the pattern of secretion of LH and FSH before and after puberty in men?
As a child FSH secretion is higher than LH
As an adult LH secretion is higher than FSH
What is androgen binding protein?
A protein synthesized by FSH that is secreted into the seminiferous tubule to keep testosterone levels high
What is P-450 aromatase?
An enzyme which converts testosterone into estradiol
What are growth factorsused for in men?
Support sperm cells and spermatogenesis
What are inhibins?
Members of the transforming growth factor beta gene family which are important for feedback
What cross-talk occurs between sertoli cells and leydig cells?
Testosterone from leydig cells acts on sertoli cells
Estradiol and growth factors from sertoli cells act on leydig cells
What are the five elements required for optimal spermatogenesis?
Leydig cells, sertoli cells, LH, FSH, and testosterone
What is the first step in cholesterol synthesis?
Cytochrome P-450 side-chain-cleavage enzyme removes the side chain of cholesterol to form pregnolone
How does LH impact synthesis of testosterone?
It stimulates the reaction by increasing the affinity of the enzyme for cholesterol and simulating synthesis of the enzyme
What is the second step of testosterone synthesis?
17alpha-hydroxylase adds a hydroxyl group to pregnolone, forming 17alpha-hydroxy-pregnolone
What is the third step of testosterone synthesis?
17,20-desmolase removes the side chain from 17alpha-hydroxypregnenolone to form dehydroepiandrosterone
How do androgen receptors function and what family are they from?
Function as homodimers and from the nuclear receptor family
What sites in the DNA do activates steroid hormone receptors bind to?
Hormone response elements
What is most testosterone bound to in circulation?
Sex-hormone binding globulin, serum albumin, and corticosteroid-binding globulin
Interactions between what two elements cause increased transcription, leading to the synthesis of specific proteins involved in growth and development?
Androgen-AR complex and nuclear chromatin
What occurs alongside the drop in testosterone levels associated with aging men?
Decreased bone formation, muscle mass, growth of facial hair, appetite, and libido
Where is testosterone metabolized?
The liver and prostate
What are androgenic and anabolic effects of testosterone?
Androgenic are growth of the reproductive tract and development of secondary sex characteristics
Anabolic are growth-promoting effects on somatic tissue
What can abnormal retention of the testes cause?
Severe damage to the seminiferous tubules and diminished testicular function
What nervous system do the testes, epididymis, male accessory glands, and erectile tissue receive innervation from?
Sympathetic and parasympathetic systems
What additional regions does the penis receive innervation from and how?
Somatic efferent and afferent systems via the pudendal nerve
How do parasympathetic and sympathetic innervation get to the penis?
Via the pelvic nerve, and the right and left hypogastric nerves
What happens to the corpora cavernosa during erection?
The smooth muscle relaxes and there is increased blood flow, which increases the volume and rigidity of the tissue
What does NO do for a penis becoming erect?
Diffuses to the vascular smooth muscle cells and causes vasodilation
What does tonic sympathetic activity do to the penis?
Causes flaccidity
What does contraction of the striated ischiocavernosus muscle do during the final phase of erection?
Increases pressure inside the corpora cavernosa
What does contraction of the striated bulbospongiosus muscle do during erection?
Increases engorgement of the corpus spongiosum
What is erectile dysfunction?
Inability to develop or maintain an erection during sexual act
What medications can be used to treat erectile dysfunction?
Sildenafil, vardenafil, and tadalafil
How do oral treatments of erectile dysfunction work?
They prevent the degradation of cGMP
What is seminal emission?
Movement of the ejaculate into the prostatic or proximal urethra
How does emission occur?
There are peristaltic contraction of the ampullary portion of the vas deferens, seminal vesicles, and prostatic smooth muscle
What is retrograde ejaculation?
The sphincter of the bladder fails to constrict, so there is semen entering the urinary bladder
What can be used to treat ejaculatory dysfunction?
Phentolamine, ephedrine, and imipramine
What is present in the cortex of the ovary?
Developing follicles and corpus luteum, and the stroma
What is present in the medulla?
Large blood vessels and other stromal elements
When are FSH levels higher than LH and when are LH levels higher than FSH?
FSH levels are higher before puberty and during menopause
LH levels are higher during the reproductive years
How do the levels of estrogen required to suppress gonadotropin output change as you age and why?
They increase as you age, because the sensitivity of the hypothalamic-pituitary system to inhibition falls
How is GnRH released?
In a pulsatile fashion once per hour
How much LH is released due to GnRH in the early and late follicular phases?
In the early phases there is a small rise in LH
In the late phase there is a large release of LH
Where is the pulse generator for GnRH located?
The arcuate nucleus of the medial basal hypothalamus
What does continuous release of GnRH cause?
Downregulation of gonadotrophs GnRH receptors, which suppresses gonadotropin release
Where do LH and FSH act?
Theca cells and granulosa cells respectively
At what concentrations do estrogens and progestins exert negative feedback?
Estrogens work at low or high concentrations
Progestins work only at high concentrations
When do estrogen and progesterone cause positive feedback?
At the end of the follicular phase
What do inhibins do in females?
Inhibit FSH secretion by the gonadotrophs of the anterior pituitary and decrease androgen production
What do activins do in females?
Increase FSH release and stimulate estrogen synthesis
What are the goals of treatment using pulsatile GnRH or continuous GnRH?
Pulsatile GnRH increases gonadotropin secretion and continuous GnRH inhibits gonadotropin secretion
What is Kallmann syndrome?
Disordered migration of GnRH cells during embryonic development which leads to hypogonadotropic hypogonadism and anosmia
What is endemetriosis?
Abnormal presence of endometrial tissue outside the uterine cavity
How does continuous secretion of GnRH treat endemetriosis?
It inhibits the replenishment of the receptor for GnRH in the gonadotrophs in the anterior pituitary, which diminishes seretion
How does continuous administration of GnRH treat leiomymas?
Proliferation of lesions is reduced
What is required for estrogen synthesis during the follicular phase?
LH, FSH, theca cells, and granulosa cells
What is required for estrogen synthesis during the luteal phase?
LH, FSH, theca-lutein, and granulosa-lutein cells
What do theca and theca-lutein cells do in estrogen synthesis?
Take up cholesterol and produce adrenal androgens using 17alpha-hydroxylase and 17,20-desmolase
What do granulosa and granulosa-lutein cells do in estrogen synthesis?
Use aromatase to make estrogen
What are granulosa-lutein cells able to do during the luteal phase due to LH binding?
Synthesize large amounts of progesterone
What kind of receptors do theca and granulosa cells have?
Theca cells have only LH receptors
Granulosa cells have LH and FSH receptors
During which phase is estrogen high and which phase is progestin high?
Estrogen is high during the follicular phase and progestin is high during the luteal phase
What does the formation of the corpus luteum do to granulosa-lutein cells?
Increases vascularity which facilitates delivery of LDL cholesterol
What happens to androstenedione produced in the theca-lutein cells?
It moves to the granulosa-lutein cells for aromatization and formation of estradiol
What is the principal function of estrogen?
Stimulate cellular proliferation and growth of sex organs and other tissues related to reproduction
What is most estrogen in the blood bound to?
Sex-hormone binding globulin and albumin
What do progestins stimulate in reproductive tissue?
Glandular secretion
What are the phases of the ovarian cycle?
The follicular phase and the luteal phase
What are the phases of the endometrial cycle?
Menstrual phase, proliferative phase, and the secretory phase
In what state does the endometrium go into after birth, which it stays in until puberty?
Regressed state with glands that are atrophic and lack vascularization
What occurs in the follicular phase and the luteal phase?
In the follicular phase the follicle develops
In the luteal phase the remaining follicular cells develop into the corpus luteum
What occurs in the menstrual phase?
Estrogen and progesterone levels are reduced and the corpus luteum, and the vascular and glandular integrity of the endometrium degenerates.
What is left in the uterus after menses?
A thin layer of non-epithelial stromal cells
Where do epithelial cells remain after mesntuation?
In the lower uterine segments and around the fallopian tubes
What causes the endometrium to be restored in proliferative phase?
Proliferation of the basal stromal cells on the denuded surface of the uterus
What stimulates proliferation and differentiation of the endometrium?
Estrogen
What does estrogen induce the synthesis of?
Growth factors and progestin receptors
What does progesterone do during the proliferative phase?
Opposes estrogen by turning it into inactive substances and inhibits epithelial cell proliferation. It promotes proliferation of the endometrial stroma
What does progesterone stimulate in the early luteal phase?
Increase in secretory activity by glandular cells
What occurs in the late secretory phase to the endometrium?
Vascularization
What is predecidualization?
Stromal cells that surround spiral arteries of the uterus enlarge and develop eosinophilic cytoplasm with prominent golgi and ER
What makes up the zona compacta?
Decidual cells spreading throughout the upper layer of the endometrium
What allows the zona spongiosa to be distinguished?
Edema of the midzone of the endometrium
What makes up the functional layer of the endometrium?
The superficial zona compacta and the mid-level zona spongiosa
What is the functional layer of the endometrium?
It is the layer that proliferates early in the cycle, interacts with the embryo, and is shed after pregnancy or during menstruation.
What is the deepest later of the endometrium?
The zona basalis
What is sometimes referred to as the ischemic phase?
Rhythmic spasms and relaxation of the spiral arteries
Why doesn’t menstrual blood clot?
Due to fibrolysins released from necrotic endometrial tissue
What are the three types of birth control pill?
Monophasic, multiphasic, and progestin-only
How do oral contraceptives work?
They decrease the secretion of gonadotropin releasing hormone
What do low levels of LH and FSH from oral contraceptives cause?
Low FSH causes insufficient stimulation for normal folliculogenesis
Low LH prevents ovulation
What occurs in menopause?
Cyclic reproduction function ceases, menstruation comes to an end, and childbearing is no longer possible
What are the four phases of sexual response?
Excitement, plateau, orgasm, and resolution
What controls most of the excitement in female arousal?
Parasympathetic fibers emanating from the sacral plexus
What coordinates female orgasm?
The spinal cord reflex that results in rhythmic contractions of the perineal muscles
Which nerve is the primary intervention to the perineum and the female external genitalia?
Pudendal nerves
Where does fertilization occur?
The ampulla, which is the upper third of the fallopian tube
What is capacitation?
A physiological process which spermatozoa must undergo to acquire the ability to penetrate the zona pellucida of the ovum
What is the acrosomal reaction?
A process by which the membrane surrounding the acrosome fuses with the plasma membrane of the sperm to liberate the contents of the acrosome due to increased internal calcium levels
What does the sperm-ZP3 interaction cause?
The acrosomal reaction to occur
What does the increase in intracellular calcium from the acrosomal reaction cause in the egg?
The oocyte’s second meiotic division and the cortical reaction
What does the cortical reaction cause?
Hardening of the zona pellucida
What are the nucleus of the mature egg and sperm cells called?
The male and female pronucleus’
What does the fertilized ovum turn into in the fallopian tube?
Morula
What is a blastocyst?
A ball-like structure with a fluid-filled inner cavity
How long after ovulation does implantation occur?
6-7 days
What occurs in predecidualization?
Stromal cells transform into decidual cells
How does the blastocyst avoid rejection?
Releasing immunosuppressive agents
What does hCG do?
Sustains the corpus luteum in the face of rapidly falling LH levels and is immunosuppressive
What is ovarian stimulation?
Obtaining multiple oocytes by giving high doses of gonadotropin to trigger the development of numerous follicles
What is oocyte retrieval?
Oocytes are recovered by aspirating them from individual follicles
What is intracytoplasmic sperm injection?
Micromanipulation techniques are used to inject a sperm cell into the cytoplasm of each egg
What is human placental lactogen (hCS1 and hCS2)?
Polypeptide hormones which facilitate the energy supply to the developing fetus
What can hPL do to the mother?
Reduce insulin sensitivity causing hyperglycemia and gestational diabetes
What is the major source of progesterone and estrogen after 8 weeks of gestation?
The placenta
What portions of hormone synthesis is the placenta not capable of?
Manufacturing adequate cholesterol, and lacks three enzymes needed to synthesize estrone, estradiol, and estriol
What changes in the mother during pregnancy?
Increase in cardiac output, blood volume, alveolar ventilation, and demand for protein, iron, and folic acid.
What are prostaglandins produced from?
Arachidonic acid
What happens in the direct pathway for prostaglandin production?
An agonist binds a receptor which activates phospholipase A, and then phospholipase A releases arachidonic acid from the membrane phospholipids
What is produced from the cyclooxygenase pathway of arachadonic acid?
Thromboxanes, prostacyclins, and prostaglandins
What is produced in the 5-lipoxygenase pathway of arachidonic acid?
Leukotrienes
What is produced in the epoxygenase pathway of arachidonic acid?
HETEs and EETs
What promotes the uterus to be quiescent?
Progesterone and relaxin
What are the characteristics of stage 0 of labour?
Uterine tranquility and refractoriness to contraction
What are characteristics of stage 1 of labour?
Uterine awakening
From the initiation of parturition to complete cervical dilation
What are characteristics of stage 2 of labour?
This is active labour
From cervical dilation to the delivery of the fetus
What are characteristics of stage 3 of labour?
This is the birth
From the delivery of the fetus to the expulsion of the placenta
Which two prostaglandins are highly involved in uterine smooth muscle contraction?
PGF and PGE
What stimulates decidual cells to increase their PGF synthesis?
Oxytocin
What are the three major effects of prostaglandins?
Stimulation of uterine smooth-muscle contraction, promotes the formation of gap junctions between uterine smooth-muscle, and induction of softening, dilation, and thinning out of the cervix
What does aspirin do in regards to labour?
Inhibits cyclooxygenase, which reduces prostaglandin synthesis and activity
Where is oxytocin synthesized?
The supraoptic and paraventricular nuclei of the hypothalamus
What does oxytocin cause in the uterus?
Contraction of the uterine smooth muscle and increased intrauterine pressure
How much and when do oxytocin receptros increase?
20 weeks
36 weeks increases by 80 fold
During labour increases by 200 fold
What is the primary stimulus for oxytocin release during labour?
Distension of the cervix
What does relaxin do?
Softens and helps dilate the cervix
What are the two positive feedback loops in labour?
Uterine contractions stimulate prostaglandins which increase the intensity of uterine contractions
Uterine activity stretches the cervix, which increases oxytocin causing more uterine activity
Which hormones lead to full development of breasts during pregnancy?
Prolactin, human chorionic somatomammotropin, estrogen, and progesterone
What do mammogenic hormones promote?
Proliferation of alveolar and duct cells
What do lactogenic hormones promote?
Initiation of milk profuction by alveolar cells
What do galactokinetic hormones promote?
Contraction of myoepithelial cells and thus milk ejection
What do galactopoietic hormones do?
Maintain milk production
What is cow milk higher in than human milk?
Protein from its high casein concentration and electrolytes
What effects does suckling have?
Inhibition of dopamine to allow for prolactin levels to stay high
Inhibition of GnRH to prevent LH and FSH release causing menstruation
How does dopamine inhibit prolactin?
Inhibition of cAMP production, activation of K channels, and inhibition of Ca channels
