BMS 409 Exam 2

Describe the tissue layers of the scrotum from superficial to deep

"Some damn Englishmen called it the testis" S: skin D: dartos fascia and muscle E: external spermatic fascia C: cremasteric fascia I: internal spermatic fascia T: tunica vaginalis T: tunica albuginea

The gonads develop from what three sources

- Mesothelium: lines the posterior abdominal wall - Mesenchyme - Primordial germ cells

What are the processes known to be regulated by RA?

- spermatogonial differentiation (commitment to meiosis) - spermiation - blood-testis barrier organization - induces the expression of Stra8 which regulates meiotic prophase

At what stages of testicular degeneration are the lesions still producing oligozoospermia/teratoospermia?

0-4

A fully capacitated sperm is distinguished by

1) hyperactive motility 2) change in surface membrane properties (acrosome reaction)

Describe the 3 phases of testicular descent

1. Abdominal translocation: the gubernaculum expands due to the influence of Insl3 secreted by the Leydig cells; testes is now at the internal inguinal ring 2. Transinguinal migration: the gubernacular bulb enlarges and expands the inguinal canal 3. Inguinoscrotal migration: the gubernacular bulb continues to grow towards the bottom of the scrotum; the cephalic lig. responsible for holding the testes up is regressed by the testosterone; calcitonin gene-related peptide moves the testes downward

Describe the thermoregulation of the testis

1. Contraction of the cremaster and tunica dartos muscles 2. Conduction: venous blood is pushed to the scrotal skin 3. Evaporation: from scrotal skin via sweat 4. Heat exchange via the pampiniform plexus

There are three normal sexual differentiation stages, in the order they

1. Establishment of chromosomal sex 2. Development of the undifferentiated gonads 3. Differentiation of the internal ducts and external genitalia

Spermatogenesis occurs in what three main phases

1. Spermatogonia: Self-renewal; mitotic proliferation 2. Spermatocytes: two meiotic divisions 3. Spermatids

List the order of chromatin arrangments in the primary rat spermatocyte through meiosis

1. primary spermatocyte 2. leptotene; filamentous 3. zygotene; bouquets 4. pachytene; crossing over, bulky 5. diplotene; completion of meiosis I (diploid) 6. secondary spermatocytes (yield haploid cells from second meiotic division)

Angiotensin II acts on what enzyme to induce the production of

18-hydroxylase and the production of aldosterone

What is the ratio of men in the United States with a sexual dysfunction?

1:3

Commonly, how many cycles are needed for completion of spermatogenesis?

4.5 cycles

The Wolffian and Mullerian duct develops at what time?

4th week; 6th week

At what stages of testicular degeneration are the lesions still producing azoospermia?

5-9 *basement membrane is the only thing that is left in these stages

What enzyme is responsible for converting testosterone to DHT?

5alpha-reductase

In the rat, how many different intermediate cell shapes occur before becoming sperm?

60

What is AGD and how is it affected in testicular dygenesis?

AGD is known as the anogential distance ands the distance from the anus to the genitalia.It is regulated by dihydrotestosterone, which can be disrupted by phthalates common in plastics. The AGD is determined during the first 12 weeks of gestation.

Name the three Y chromosome microdeletions and the affects

AZFa deletion --> azoospermia, Sertoli cell-only syndrome AZFb--> azoospermia, spermatogenic arrest AzFc--> severe oligozoospermia to non-obstructive azoospermia

What are the functions of the epididymis?

Absorbs most the fluid that leaves the testis, endocytoses and secretes proteins, and phagocytoses defective sperm

Describe how activins are named

Activins are homodimers or heterodimers and members of the TGF-beta superfamily *Beta subunits only Activin A (betaA - betaA), Activin B (betaB - betaB)

What methods have been developed to treat prostate cancer?

Administration of GnRH receptor agonists --> see the development of female secondary sex characteristics This will reduce the concentration of testosterone and DHT which is in excess is known to increase the size of the prostate

What is the impact of AR knockout in Leydig cells?

Affects steroidogenic functions leading to arrest of spermatogenesis at the round spermatid stage

Who performed the classical experiments to delineate the roles of hormones in sexual differentiation

Alfred Jost --> experiments on rabbit embryos

Describe the asynchronous cycle of spermatogenesis in humans

Along the length of the tubules, spermatogonia commit to further differentiation at different spots at different times. This asynchronous cycle is essential for continual sperm production.

Describe the ways in which hormones affect the sexual differentiation of the brain

An experiment completed on rats showed that females injected with testosterone had a significantly larger sexually dimorphic nucleus than the control females. These females then proceeded to exhibit male mounting behaviors. SDN volume is reduced in castrated males compared to that of normal males. These males exhibited female roles during intercourse. Conclusion: Testosterone masculinizes and feminizes rat brains

What is the end product(s) in immature Leydig cells?

Androstanediol

What is the end product(s) in progenitor Leydig cells?

Androsterone

Describe the autocrine axis in the testis that coordinates spermiation and BTB restructuring during spermatogenesis

At spermiation, laminin fragments are released by the disrupted apical ES which prepares the BTB to allow the prepleptotene spermatocyte to enter the adluminal compartment.

At 6 weeks gestation, the fetus is considered

Bipotential; the gonads are undifferentiated at this point in time, but the chromosomal sex of the develping fetus has been determined

What can cause male pseudohermaphroditism?

Broadly speaking, male pseudohermaphroditism can be caused by a deficiency of androgen synthesis, conversion, or action. More specifically, it can be caused by: - Impaired testosterone synthesis caused by a deficiency of 3-beta-hydroxysteroid dehydrogenase - Impaired conversion of testosterone DHT caused by 5-alpha- reductase deficiency - Impaired binding of androgen to its receptor caused by androgen receptor deficiency

Describe the capacitation and the acrosome reaction

Capacitation begins when the coating glycoproteins are removed, increased pH, and Ca2+ entry and cholesterol efflux. It allows spermatozoa to penetrate the zona pellucida and fuse with the oocyte membrane. Spermatozoa unable to undergo the acrosome reaction will not fertilize intact oocytes. The acrosome reaction occurs when there is fusion between the plasma membrane and acrosomal membrane of the sperm.

What are the three distinct regions of the epididymis?

Caput (head), corpus(body), and cauda (tail)

Testicular feminization syndrome

Cause: deficiency of androgen receptor, mutation from Glutamate to Glycine X-linked recessive gene mutation maintains normal testosterone synthesis, no androgen receptor results in no differentiation of Wolffian duct and urogenital sinus, accumulation of testosterone becomes aromatized to estradiol which results in secondary female characteristics, no uterus because the Müllerian duct regresses Symptoms: think like a male but look like a female

Kallmann syndrome

Cause: failure of GnRH neurons to migrate to hypothalamus; KAL protein is absent Symptoms: Olfaction and GnRH neuronal functions is disturbed; no sense of smell; patients remain prepubertal without GnRH

What happens in human if the LHCG receptor is mutated?

Causes pseudohermaphrodite phenotype in genetic males due to the lack of intrauterine masculinization due to defective fetal Leydig cells testosterone production

21- and/or 11-Hydroxylase deficiency

Causes: Impairs the synthesis of cortisol and aldosterone. This resultant decrease in feedback inhibition causes increased secretion of ACTH leading to adrenal hyperplasia and increased testosterone Symptoms: Development of male characteristics; increased loss of salt leading to vomiting, weight loss, and adrenal crisis Males: Normal at birth but over masculinized feature prior to puberty Females: pseudohermaphrodites

Describe the pathology of Klinefelter's syndrome

Classified as a non-disjunction sexual disorder, Klinefelter's disease occurs when the embryo has a sex chromosomal designation of XXY. On of the X chromosomes is inactived. This is the MOST frequent cause of hypogonadism, with an occurrence in every 1 out of 500 people. The symptoms include: micropenis, small firm testis, increased levels of estrogen and FSH, and breast development. NOTE: X-inactivation is random --> can inactive the X supplied from Mom or Dad

Function of the tunica dartos

Comprised of smooth, involuntary muscle Fxn: form the scrotal septum which divides the scrotum into two sacs

Function of the cremasteric fascia

Comprised of voluntary striated muscle Fxn: control proxitiy of the testis to the body

What is the end product(s) in fetal Leydig cells?

Corticosterone Androstenedione

What molecule is responsible for converting the urogenital sinus into the prostate, scrotum, and penis?

DHT

What gene is classified as an anti-testis gene?

Dax1

Describe hyperprolactinemia and its causes

Dopamine inhibits the release of prolactin. Hyperprolactinemia causes the hypersecretion of prolactin which causes the hypersecretion of dopamine. This increase in dopamine concentration, in turn, causes the decreased release of GnRH → LOSS of trophic hormone release. Symptoms include: sterility, decreased libido, impotence

Describe rertograde ejaculation

During ejaculation, the sympathetic activity contracts the internal bladder sphincter, isolating the bladder from the urethra. During retrograde ejaculation, semen enters into the bladder instead of going out through the penile urethra during ejaculation.

Describe the effect of Bisphenol-A on the prostate

During embryo development, BPA can reprogram the prostate progenitor cells to promote self-renewal and increase in vivo carcinogenesis when exposed to estrogen/androgen.

Describe how erectile dysfunction drugs function

ED drugs inhibit the degradation of cGMP by PDE5 --> causes prolonged erection

In what ways can EDCs inhibit the actions of endogenous hromones by binding to hormone receptors as well as sex hormone-binding proteins

EDCs can mimic hormonal function (produces response) or block hormone function by binding to the hormone receptor

What are the two functions of androgen-binding protein?

Elevating androgen levels in the local environment to sustain spermatogenesis and enters the epididymis to drive sperm maturation

Effects of 5alpha-reductase mutation

External female genitalia prior to puberty; elevated T to DHT levels; following puberty and the surge of testosterone, phenotype changes to male but the prostate remain small Genetically males that obtain and autosomal recessive gene that mutates both copies of the SRD5A2 gene

What two molecules act synergistically on Sertoli cells to promote Sertoli cells function and the support of spermatogenesis

FSH and androgens

What is the major factor regulating Sertoli cell maturation in the pre- and post- pubertal testis

FSH plays a role in Sertoli cell proliferation; thyroid stimulating hormone inhibits Sertoli cells proliferation

T/F Germ cells have receptors for androgen binding protein

False

T/F Sperm makes up a large percentage of ejaculate.

False

T/F Sertoli cells are capable of proliferating after they are fully differentiated.

False; the Sertoli cell is terminally differentiated at this point and is unable to proliferate.

T/F Many seminal plasma constituents primarily act as a medium supporting the fertilizing sperm

False; the seminal plasma constituents primarily act on the female tract

What is the current hypotheses on the origins of fetal and adult Leydig cells?

Fetal and adult Leydig cell populations have distinct cell lineages with separate origins

Development of the Leydig cells occurs in the testes in most mammalian species as two distinct phases, these are?

Fetal and pubertal phases *primates have a third phase called the neonatal growth phase

Describe prostatic development

Following the conversion of testosterone to dihydrotestosterone via 5-alpha-reductase, DHT binds to the androgen receptors on the surface of the ductal tips, which activates a signaling cascade that ends in the expression of structures inherent to the prostate

When deleted, what two genes can lead to sex reversal?

Fox12 Dmrt1

In terms of steroidgenesis what parts of the pathway occur in the Leydig cells? Sertoli cells?

From cholesterol to testosterone occurs in the Leydig cells, while from testosterone to estradiol occurs in the Sertoli cells

What are the components of semen in order of highest content to lowest content?

Fructose, electrolytes, mucus, and sperm

What can be said about the approximate volumes of ejaculum between species?

Humans have a low volume of ejaculate; the size of the accesory sex glands positively correlates the volume ejaculate

Describe hypospadiac development of the penis

Hypospadiac development of the penis is caused by the incomplete fusion of the urethra-associated erectile bodies. Absences of the ventral wall of the urethra, corpus spongiosum, or ventral penile skin which causes a urinary opening at a location outside of the head of the penis.

What are the molecules secreted by the Leydig cells

INSL3 oxytocin estradiol testosterone

Function of insulin-like protein 3 and oxytocin

INSL3: promotes sperm meiosis Oxytocin: stimulate myoid cells to contract, moving sperm to excurrent ducts Both products diffuse in the Sertoli cells where they act respectively

Describe the spatial organization of the seminiferous tubules in humans

In most animals, there is a continuous wave of spermatogenesis going on in an orderly fashion along the length of the seminiferous tubule. In the human, however, there is a mosaic arrangement fo the sex stages of spermatogenesis.

Describe the role of retinoic acid in meiosis in males and females

In the female ovary, RA is generated in the mesonephros and drives the expression of Stra8 and the onset development of female characteristics. In the male, RA is still produced in the mesonephros, however, CYP26B1 degrades RA thereby preventing the expression of Stra8.

What happens in mice if pituitary LH is mutated?

In the mouse, the fetal Leydig cells androgen production is possible in the absence of pituitary LH or LHR, because various paracrine factors are capable of inducing the fetal Leydig cell to produce testosterone and cause intrauterine masculinzation

Describe how inhibins are named

Inhibins are heterodimers of alpha and beta subunits Inhibin A (alpha-betaA) Inhibin B (alpha-betaB)

Describe the mutations that can be caused by BPA (Bisphenol A) in the developing fetus

Interferes with spindle formation during meiosis which can increase the risks for errors in chromosome segregation; this can be classified as interfering with recombination.

How are pitch and testis size related in howler monkeys?

Inversely related; the lower the pitch the smaller the testis

Describe the interactions between Sertoli cells and Leydig cells

LHR follows a PKA pathway which activates the conversion of cholesterol to testosterone in the Leydig cells. The testosterone then travels to the Sertoli cells and is converted to estradiol via aromatase. Estradiol then acts on the Leydig cells to promote new protein synthesis.

LH binds to receptors on what cells type

Leydig cells

What cell type is considered the primary source of testosterone in males?

Leydig cells

Function of estradiol in Leydig cells

Leydig cells produce estradiol which binds to estradiol beta receptor to stimulate the proliferation of spermatogonia

Explain the role of testosterone in the context of Leydig cells and Sertoli cells

Leydig cells synthesize and secrete testosterone which diffuses into Sertoli cells and binds to its androgen receptor, which in turn activates the transcription of genes that promote spermatogenesis.

Describe the effects of 5-alpha-reductase inhibition in steroidogenesis

Loss of DHT production

Effects of 17-alpha-Hydroxylase mutation

Loss of sex hormone production; phenotypically female, but UNABLE to mature; shunts precursors in the aldosterone pathway

Effects of mutant 17-beta HSD

Loss of testosterone production, elevated estrogen levels, phenotypically female

What genes are associated with determining whether the indifferent gonad will differentiate as male or female respectively?

Male: Sry; Sox9 Female: Rspo1 via Wnt4, and Dax1

Describe the differentiation of the internal ducts in terms of each gender

Males: differentiation of the Wolffian (mesonephric duct) and regression of the Mullerian (paramesonephric duct) Females: differentiation of the Mullerian (paramesonephric duct)

Species differences in testicular descent

Mammals are the only vertebral group that has species with scrotal testes. The testes may remain in their original internal location, or descend but remain in the body cavity, or descend into scrotal sacs. In order to a scrotal testes to be functional in a mammals it MUST descend into the scrotum. There are many theories as to why mammals have scrotal testes, but all intangible.

Follow the pathway of primordial germs cells throughout the development of the gonadal ridge

Mesoderm --> base of the allantois --> endoderm --> mesentary --> genital ridge On their way to the genital ridge, PGCs will proliferate extensively via mitosis. Stem cell factor (SCF) and c-kit are responsible for the survival of migratory PGCs. c-kit is present on the surface of the PGCs and SCF is found along the migratory route to the genital ridge. This migration is also controlled by TGF-beta1 which acts a chemoattractant but inhbits the proliferation of the PGCs to control numbers in the gonad.

What is the impact of AR knockout in germ cells?

NO affect on fertility or spermatogenesis

What molecule is responsible for stimulation an erection?

NO aka nitrous oxide

Cause of non-disjunction disorders

Occurs when fertilization occurs between gametes with non-disjunction in sex chromosomes XXY - Klinefelters X0 - Turner's Y0 - Lethal

Describe the effects diethylstillbestrol in women

Originally was used in utero to prevent miscarriages and caused clear-cell adenocarcinoma of the vagina. The condition was trans generational and led to premature babies and miscarriages in the DES daughters.

Describe the Mullerian agenesis of animals

Otherwise known as "freemartinism," this defect occurs when a female twin shares a placenta with a male twin. If the fluids of the placentas are mixed between the two fetuses, the development of the reproductive organs of the female will be impaired by the AMH produced by the male. The male is unaffected. It is is important to remember, that the male reproductive organs develop BEFORE the female, which is why AMH has such a profound impact on the female, and not the other way around. The female calf will be rendered infertile.

LH and FSH follow what kind of pathway in their respective cells types

PKA pathway

Describe the reflex pathway for erection

Physiologically, erection is triggered by the parasympathetic division of the autonomic nervous system (ANS), causing nitric oxide (a vasodilator) levels to rise stimulating gunylate cyclase to convert GTP to cGMP. cGMP then activates protein kinase causing Ca2+ to move into the smooth ER. This causes smooth muscle to relax and increase blood flow to the penis.

What is the primary difference in the conversion of androgens to estrogens in prepubertal humans and post-pubertal humans?

Prepubertal: occurs predominantly in the Sertoli cell Post-pubertal: occurs predominantly in the Leydig cells

Describe the role of prolactin in males

Prolactin plays a role in the synthesis of testosterone via the upregulation of LH receptors on Leydig cells. The local activity of androgens is enhanced by prolactin.

Describe the relationship of GnRH, LH, and FSH in the male

Pulsatile release caused by GnRH secretion and the subsequent production of LH/FSH

What is the function of estrogen in the male reproductive tract?

Responsible for concentrating sperm in the efferent duct; without estrogen, the sperm is diluted resulting in infertility. Molecule responsible for the reabsorption of 90% of luminal fluid --> increases sperm concentration

What genes are responsible for forming the sexually indifferent gonad ?

SF1 and WT1

What genes promote the differentiation into male or female structures?

SF1, WT1, and Wnt-4 (female)

Describe the structure and function of sex hormone-binding globulin

SHBG is a mixture of different hormone-binding globulins, each of which has different structures and subsequent affinities for testosterone and estradiol → transport protein Function: binds to testosterone and estradiol - This can be affected by obesity and gender

What kinds of diagnostic procedures that can be used to detect prostate cancer?

Screening for prostate specific antigen (PSA) in the blood

The blood-testis barrier is formed between what two cells

Sertoli cell to Sertoli cell

What cell is responsible for secreting androgen-binding protein

Sertoli cells

Androgens enter what cell type and what subsuequent reaction to occur here

Sertoli cells; conversion of testosterone to dihydrotestosterone

What secretes AMH and what is its function?

Sertoli cells; regress the Mullerian ducts

What is the only sex-related gene expressed solely in the developing gonad?

Sry

When does the secretion of RA peak?

Stage VII of spermatogenesis

Describe the compartments of the Sertoli cell

Starting from the bottom, there is the basal membrane, adluminal compartment, and the lumen. A Sertoli cell is considered from basal membrane to lumen.

What happens in humans if pituitary LH is mutated?

Steroidogenesis is unaffected because if it is eliminated hCG can still act on the LHCGR receptor causing the production of testosterone and male differentiaiton

Symptoms and cause of Rokitansky syndrome

Symptoms: absences/hypoplasia of uterus and vagina Cause: Ovarian granulosa cells produce AMH; if more is made prenatally or a more potent form is produces, or if the receptor is mutated to always be "on," the female can have Mullerian agenesis

What can occur during testicular torsion? Hydrocele?

Testicular torsion: occurs when the spermatic cords are twisted, causing the venous drainage from the testis to be compromised Hydrocele: occurs when there is a collection of fluid between the two layers of tunica vaginalis which can cause testicular degeneration and the loss of germ cells

What is the end products(s) in adult Leydig cells?

Testosterone Androstenediol

What can be the cause of hypogonadism?

Testosterone deficiency, Sertoli cells dysfunction, or direct impact on germ cells

How are testosterone and AMH involved in differentiation of the male phenotype?

The Leydig cells produce testosterone, which promotes development of the Wolffian ducts. The Sertoli cells produce Müllerian inhibiting substance (Anti-Müllerian hormone, AMH), a peptide hormone that causes the Müllerian ducts to regress.

What is the impact of AR knockout in Sertoli cells?

The Sertoli cell function of supporting and nurturing the germs cells in compromised; leading to the spermatogenesis arrest at the primary spermatocyte prior to the first meiotic division

What system (male/female) develops first?

The Wolffian ducts develop prior to the Mullerian ducts

What are the main differences between different LC types?

The androgenic end products and the capacity of fetal Leydig cells to produce glucocorticoids

Describe the blood-testis barrier in terms of its location and function

The blood-testis barrier is a physical barrier between the blood vessels and the seminiferous tubules of the animal testes. The name "blood-testis barrier" is misleading in that it is not a blood-organ barrier in a strict sense, but is formed between Sertoli cells of the seminiferous tubule and as such isolates the further developed stages of germ cells from the blood. It is comprised of myoid cells and tight junctions.

Describe the differentiation of the external genitalia in males

The cloaca membrane divides into the urogenital sinus and rectum. The urogenital sinus will then develop into the urinary and reproductive organs. Signals produced by the cloaca will initiate penis formation. The signals that produce this differentiation comes from the hormone dihydrotestosterone; without it, the penis, scrotum, and prostate would not develop.

How is the structure of the pampiniform plexus related to its function

The coiled structure provides a lot of space for heat exchange and the regulation of the temperature of the testis

What is meant by the statement "gender must actively be maintained"?

The deletion of a single gene is sufficient to induce transdifferentiation of gonads in adult mice. Deletion of Dmrt1 in the testis can lead to the appearance of female characteristics, and the deletion of Fox12 in the ovary can lead to the appearance of male characteristics.

What is the difference between steps and stages?

The differentiating spermatids are defined as numbered steps based on their features and products and the association with other distinct germ cell types. They have been used to divide the cycle of seminiferous epithelium into definite stages. Stages are well-defined associations of arranged developing germ cells. There are steps within stages.

Describe the interesting special feature of the fetal testis in terms of steroidogenis cascades

The distribution of 17beta-HSD that converts androstenedione to testosterone is confined tot he Sertoli cells of the tubular compartment, thus making fetal testosterone production in mice dependent on the interplay of two cellular compartments. In adult cells, it is confined to Leydig cells.

Describe the differentiation of Type A spermatogonia and Type A1 spermatogonia

The expression of Stra8 (regulates meiotic prophase) in spermatogonia is stimulated by RA in the postnatal testis. This causes the undifferentiated type A spermatogonia to convert to differentiated type A1 spermatogonia.

Describe the indifferent gonad

The indifferent gonad consists of a medulla and cortex. In males, the medulla will develop into the testes and the cortex will decline. In females, the ovary will develop from the cortex, and the medulla will decline.

Describe the changes to the sperm during spermiogenesis

The large, round euchromatic head of the spermatid is condensed into heterochromatin. The head is then re-shapes by the manchette and development of the acrosome.

Describe the formation of the genitial ridge and primary sex cords

The mesothelium proliferates to form the genital ridge at around 2-3 weeks gestation; consists of a bulge of tissue. From the same epithelium, the primary sex cords penetrate the mesenchyme.

How do intermediate stages in spermatocytogenesis relate to sperm production efficiency?

The more intermediate stages the more sperm production. Humans do not have as many intermediate stages in comparison to other species, resulting in lower sperm production efficiency percentages.

How do the cells of the ductus defrens changes as you move from proximal to distal?

The muscle activity increases to allow for contraction

What is the correlation between age and replication errors in human spermatogenesis?

The older you get, the higher frequency of replication errors. Every time there is a spontaneous mutation during spermatogenesis, all the progeny are defective.

Seminal plasma

The seminal plasma mediates the chemical function of the ejaculate.The mixing together of the various glandular fractions leads to a coagulation of the fresh ejaculate in the rear vaginal cavity within a minute. Contains ~2000 proteins and prostaglandins.

What is the general significance of type A spermatogonia?

They develop from stem cells and mark the beginning of spermatogenesis

What is meant by the term "pseudohermaphrodite"?

This is a state in which the gonads are of one sex, but there are contradictions in the morphologic criteria of sex. In other words, the chromosomal sex does not match the phenotypic sex.

T/F Prolonged incubation in seminal plasma damages sperm in certain species.

True

T/F The gonadal ridge is bipotential

True

T/F Testosterone secretion is exocrine and endocrine.

True Endocrine--> carried to brain and accessory sex organs Exocrine --> tubule lumen to be bound to androgen binding protein

T/F Leydig cells are capable of proliferating after they are fully differentiated.

True; once established, adult Leydig Cells turn over slowly during adult life.

Importance and cause of cryptochidism

Undescended testes, or cryptochidism, confers an increased risk of testicular cancer and infertility. The process of testicular descent should be completed prior to birth. The cause is currently unknown and regarded as complex and multifactorial. Following birth, the fetus can be injected with a shot of hCG, activated the release of testosterone from the Leydig cells. This surge of testosterone can cause the subsequent descent of the testes.

Match each gland to its secretion (serous or mucous): Vesicular gland Prostate gland Bulbourethral gland

V: serous P: serous B: mucous

Seroli cells are responsible for secreting what products when bound to what hormone

When bound to FSH, Sertoli cells secrete inhibin and activin

When is the blood-testis barrier restructured?

When the mature spermatids prepare for spermiation at stage VIII, the BTB opens to facilitate the transition of the pre-spermatocytes from the basal to the adluminal compartment.

Paraphimosis

acquired penile disorder caused by the foreskin being retracted over the glans and cannot be replaced to its normal position

Priapism

acquired penile disorder that causes painful, persistent erection

Phimosis

acquired penile disorder that is caused by the inability of the uncircumcised foreskin to retract over the glans

What are the three barriers present in the BTB and BEB?

anatomical barrier: restricts passage of molecules in and out of the lumen physiological barrier: comprised of transporters that regulate the movement of substances in or out of the lumen Immunological barrier: limits access of immune cells into contact with germ cells

Gubernaculum

anchors the testes at the distal end

What molecule is responsible for stimulating the upregulation of receptors for FSH on Sertoli cells?

androgens

Leydigs cells synthesize what products

androgens and oxytocin

Vinclozolin

anti-androgenic pesticide Exposure symptoms: decreases the size of the suprachiasmatic nucleus; decrease in the number of immunoreactive GnRH neurons --> impairs sexual behavior

Describe the role of androgen-binding-protein in the Sertoli cell

binds to testosterone and makes it available in the lumen → necessary for spermatogenesis

Radiation and chemotherapeutic drugs target what phase of spermatogenesis

blocks mitosis between the spermtogonium and the primary spermatocyte

BPH, benign prostatic hyperplasia

caused by excessive DHT due to increased activity of 5-alpha reductase; causes an enlarged prostate

Function of the visceral vaginal tunica

covers the testis, epididymus, and components of the spermatic cord

What is the impact of AR knockout in smooth muscle cells and myoid cells?

decreased sperm count, but still fertile

Teratozoospermia

defective sperm

The steroidogenic pathway towards the production of testosterone in Leydig cells follows what pathway type

delta 5 pathway

Function of the albuginea

dense fibrous tissue layer that covers testicular parenchyma

What does the Mullerian duct become?

develop into the fallopian tubes, the uterus and the upper part of the vagina

What does the Wolffian duct become?

differentiate to form the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts

Statins

drugs used to lower cholesterol in the bloodstream which ultimately lowers the concentration of testosterone

Where are estrogen alpha receptors most abundantly located in the male?

efferent ductules

Sympathetic nerve fibers in the penis stimulate

ejaculation with the successive contractions of the ductus defrens

EPPIN

epididymal protease inhibitor; secreted by Sertoli cells and epididymal cells and coats the sperm. It protects the sperm from proteolytic attack thereby preventing premature capacitation.

What are the two extracellular vesicles that contribute cellular components to the developing sperm? Function.

epididymosomes and prostasomes The physiological role of prostasomes and epididymosomes implicates improvement of sperm motility and protection against attacks from the female immune defense during the passage to the egg

The blood-epididymis barrier is formed between what two cells

epithelial cells and the epididymis

Oligospermia

few sperm

Peyroni disease

formation of fibrous plaque on corpora cavernosa

What structure is responsible for the release of calcitonin gene-related peptide under the control of testosterone?

genitofemoral nerve

The formation of condensed chromatin is caused by

histone proteins

Kartagener's syndrome

immotile cilia syndrome; reduced sperm motility; causes situs inversus (wrong location of the internal organs)

Cytoplasmic droplet

in rodents, is a bulge of cytoplasm that remains attached to the neck region of the elongating spermatids at the time of spermiation. It dissociates with the sperm as it reaches the body of the epididymis.

Describe the effects of 17,20-lyase inhibition in steroidogenesis

increase production of cortisol and aldosterone in the Fasciculata and Glomerulosa

Describe the affects of 17-alpha hydrolyaxse inhibition in steroidogenesis

increased production of aldosterone in the Glomerulosa

Describe the effects of 17-beta-HSD inhibition in steroidogenesis

increased production of androstenedione in the Reticularia; loss of testosterone and estradiol production

What can be some of the outcomes that can occur with a distruption in androgen and insulin-like hormone 3 dependent development due to phtalate ester exposure?

infertility testis tumors undescended testes reduced sperm count

What serves as a marker for Sertoli cell function?

inhibin--> low levels reflect a failure to complete spermiogenesis

Sperm granuloma

is a lump of stagnant sperm that appears along the vasa deferentia or epididymides

HSD3B

localized exclusively in Leydig cells and regulates testosterone

Azoospermia

low sperm

Describe the general efficiency of sperm production in humans

lowe sperm production --> low efficiency

What source is responsible for forming the genital ridge?

mesothelium

What are the targets of environmental exposures in the sperm epigenome?

microRNAs in the epididymosome

What is one of the most commonly identifies molecular genetic cause of male infertility?

microdeletions on the Y chromosome in the AZF regions with men with normal karyotypes

What is the function of AURKC?

necessary to ensure the bi-polar attachment of the diads and participate in the meiotic spindle checkpoint and at the telophase are located at the cleavage furrow and contribute to cytokinesis

What is the function of estrogens in males

needed for excurrent duct functions

The intermediate mesoderm gives rise to what structure?

nephrogenic cord, which in turn gives rise to pronephros, and metanepros

The Mullerian duct is a (paramesonephric or mesonephric duct) and the Wolffian duct is a (paramesonephric or mesonephric duct)

paramesonephric; mesonephric

What types of nerves are responsible for erection?

parasympathetic

COUP-TFII

participates in Wolffian duct regression

Dihydrotestosterone is required for the development of what external genitalia structures

penis, scrotum, and prostate

AURKC mutation

presents a large head and several flagella in sperm; caused by abnormal binding of the microtubules to the kinetochores and premature chromosome segregation and no cell division during cytokinesis

DPY19L2 deleted patient

presents a round-shaped head and an absence of mitochondria in the midpiece

Exposure to a heat targets what phase of spermatogenesis

primary and secondary spermatocytes

A lesion in the testes can cause

primary hypergonadotropic hypogonadism

The gonads are colonized by what kinds of cells?

primordial germ cells

In mammals what structures become temporary excretory ducts, and what becomes the permanent kidney?

pronephros and mesonephros; metanephros

What kind of release is RA release?

pulsatile

USP9X

regulate the maintenance of the germ cell lineage crucial for gametogenesis; prevents unnecessary cell death --> if it is knocked out, there is little to no sperm production

Why are rodents not a good model for the HPG axis in humans?

rodents develop prior to the pituitary-dependent phase

Water disinfection by-products target what phase of spermatogenesis

sperm release

What is the function of oxytocin in males

stimulates contractility of seminiferous tubules and the epididymis

What types of innervation can be found in the penis?

sympathetic and parasympathetic

A lesion in the hypothalamus can cause

tertiary/secondary hypogonadotropic hypogonadism

The loss of what androgen can cause the loss of penile spines in cats

testosterone

What molecule is responsible for the masculization of anatomical structures?

testosterone

DNAH1 mutation

various defects of the flagellum

When is the human fetal hypothalamic-pituitary-adrenal axis considered fully functional

when the genitalia differentiate