Male Repro and Embryogenesis/Repro System Development - Lectures 4/5

Testis function

Site of gamete/hormone production

Testis structure

Tunica albuginea

Seminiferous tubules/testis parenchyma

Interstitium

Tunica Albuginea

Testicular capsule

Testis parenchyma

Tissue made up of seminiferous tubules that house developing gametes

Sertoli and germ cells

Interstitium

Space between seminiferous tubules

Location of leydig cells

Order of structures in tubules (interstitial side to lumen side)

Peritubular myoid cells

Mitotic germ cells

Meiotic germ cells

Post meiotic germ cells

Sertoli cells surround everything

What are the 3 things a mammalian gamete needs?

Immune privilege

Correct hormone signaling

Temperature homeostasis

Lack of immune privilege effects

Loss of meiotic and post-meiotic germ cells

Mitotic cells are unaffected - the body still considers them "you" as they are diploid

Fertility is recoverable - mitotic cells still there

Blood Testis Barrier (BTB) parts

Basal compartment

Adluminal compartment (primary part)

Basal compartment of BTB

First barrier against immune system

Peritubular myoid cells

Partially protected - also location of mitotic germ cells

Adluminal compartment of BTB

Created by sertoli cells closing

Covers everything after the mitotic germ cells

Fully protected

How can the BTB be tested?

If the BTB is intact, dye will only be on the outside of tubules

If not, you can see the dye permeate the tubules

Sertoli cells

"nurse cells"

Somatic cells that surround the germ cells

Secrete AMH

Effect of loss of hormone signaling in gamete production

Loss of post-meiotic germ cells

Fertility is recoverable - mitotic cells intact

Lack of androgens (testosterone)

Leydig cells

Produce testosterone

Most stays in testicles, but some is spread by capillaries

Induced by LH

Structures in interstitium (outer to inner)

Peritubular myoid cells

Macrophages blocked by BTB

Leydig cells

Capillary (spreads T through body)

Temperature homeostasis effects of fertility

Loss of all germ cells

Causes complete infertility - unrecoverable

How do testis stay cool

Temperature needs to be steady and cool relative to body

Scrotal sack is covered in sweat glands

Pampiniform plexus

Spermatic cord function

Connects testis to body

Cremaster muscle

In spermatic cord

Ligament that connects testis to body

Spermatic cord structures

Cremaster muscle

Testicular artery

Ductus deferens

Pampiniform plexus

Pampiniform plexus

Series of veins/arteries to/from scrotal sack

Veins/arteries are intertwined for heat transfer - hot blood from arteries cools itself by heating blood from veins

Allows for temperature homeostasis

Also helps distribute T through body

Primary functions of testis/testis support tissues

Gamete production

Hormone production

Excurrent ducts structures

Efferent ducts

Epididymis

Ductus deferens

Efferent ducts function

Deliver sperm to epididymis

Kinds of cells in efferent ducts

Mixed epithelium -

Smooth muscle & ciliated cells move spermatozoa

Short cells concentrate spermatozoa through water reabsorption

Epididymis function

Moving, modifying, and storing mature gametes

Epididymis structure

Single long tubule that goes back and forth

Multiple segments with different cell types to generate different environments

Surrounded by smooth muscle to help move sperm

Segments of epididymis (from efferent duct to ductus deferens)

Caput

Corpus

Cauda

Caput

Beginning of epididymis

Removal of abnormal spermatozoa

Membrane modification

Corpus

Middle section of epididymis

Sperm gain motility (ability to move on their own) as mitochondria form near tail

Cauda

End of the epididymis

Sperm gain fertilization (capacitation) ability

Long term storage

Primary site for sperm reserves

Ductus deferens function

Moving gametes

(from caudal epididymis to accessory sex glands)

Gamete maturation/delivery, seminal fluid production/delivery

Ductus deferens structure

Narrow epithelium surrounded by smooth muscle

Accessory sex glands function

Generate seminal plasma

Accessory sex glands parts

Ampulla

Vesicular gland

Prostate gland

Bulbourethral gland

Male repro - Ampulla

Widening of vas deferens

Continuation

Male repro - Ampulla cell types

Smooth muscle (moves sperm/fluid from vas to urethra)

Mucosa lining (secretes seminal fluid)

Male repro - Vesicular glands (seminal vesicles)

Similar morphology to ampulla but not contiguous (continuous/connected) to vas deferens

Vesicular glands function

Generate/store seminal fluid (majority of ejaculate)

Vesicular glands cell types

Smooth muscle

Mucosa - high surface area to produce seminal fluid

Prostate

Species specific morphology

Generates prostate fluid

Protects sperm after ejaculation

Prostate specific antigen (PSA)

Very hormone sensitive - imbalance can cause it to grow

Prostate specific antigen (PSA)

Reduces semen viscosity

Bulbourethral gland

Species specific morphology

Accessory sex gland functions

Seminal fluid production and delivery

Excretory tissues function

Gamete delivery

Seminal fluid production and delivery

Excretory tissues structure

Penis and urethra

Male repro - urethra

Contractile muscle around a duct designed for delivery

Penis

Highly evolved system with lots of variation

What part of the male reproductive tract is responsible for gamete and hormone production?

Testis

What part of the male reproductive tract is responsible for gamete maturation?

Excurrent ducts (efferent ducts, epididymis, vas deferens)

What part of the male reproductive tract is responsible for gamete delivery?

Excurrent ducts (efferent ducts, epididymis, vas deferens)

Excretory tissues (penis/urethra)

What part of the male reproductive tract is responsible for seminal fluid production and delivery?

Everything but testis -

Excurrent ducts (efferent ducts, epididymis, vas deferens)

Accessory sex glands

Excretory tissues (penis/urethra)

Target tissue for sterilization in men

Ductus deferens

2.4% worldwide

Cause of sterility in men with cystic fibrosis

Ductus deferens

Mammalian fertilization

Combines chromosomes of egg and sperm

Inherited sex chromosomes typically determine gonadal/genetic sex

Parents are diploid XX or diploid XY

Egg = haploid X

Sperm = haploid X or Y

Why is sex considered a mosaic of traits?

It is dependent on a number of factors and is not binary

Factors include:

Hormones

Genotypes

Phenotypes

Secondary sex characteristics

Internal/external genitalia

Difference between the X and Y chromosomes

X is ~3x larger

Y has the SRY gene

SRY gene

Sex determining region of the Y chromosome

Directs development of male phenotypes

Methods of sex determination

Genotypic sex determination

Temperature-dependent sex determination

Behavioral sex determination

Embryogenesis

Post fertilization process

Stages of an ovulated egg

Oocyte

Ootid (after fertilization, 2 separate nuclei)

Zygote (pro nuclei join together)

Two celled stage

Four celled stage

Eight celled stage

Morula

Early blastocyst (occurs once embryo leaves fallopian tubes)

Hatching blastocyst

Hatched blastocyst

Blastocyst

Fertilized egg divides until it is a blastocyst with 2 parts

Inner cell mass and trophoblast

Inner cell mass (ICM)

Part of the blastocyst that becomes the embryo

Trophoblast

Part of the blastocyst that becomes the placenta

ICM differentiation

During early embryogenesis the ICM differentiates to form the layers of the embryo

Ectoderm

Mesoderm

Endoderm

Ectoderm

"Outer skin"

Part of the ICM that differentiates into skin, hair, and nervous system.

Part of the reproductive tract - vagina & vestibule, penis & clitoris

Becomes hypothalamus and pituitary

Mesoderm

"Middle skin"

Forms a lot of the reproductive system - gonads, uterus cervix, vagina, epididymis, ductus deferens, accessory sex glands

Basically everything internal

Endoderm

"inside skin"

Part of the ICM

Doesn't differentiate into anything relevant to reproductive system (except endocrine system)

Hypophysis

Another word for pituitary

Produces LH/FSH which stimulates the testis/ovaries to produce testosterone and estrogen/progesterone

Neurohypophysis

Posterior hypophysis//pituitary

From neural tissue of brain floor

Stores/secretes Oxytocin and ADH (BUT DOES NOT SYNTHESIZE THEM! Hypothalamus makes them)

Ectodermal layer

Adenohypophysis

Anterior hypophysis/pituitary Derived from ectoderm in roof of embryonic mouth

Synthesizes and secretes LH, FSH, PRL, GH, TSH, ACTH

Mesodermal layer

Diverticulum

A sac/pouch diverting from a main tube/cavity

Infundibulum

Specific diverticulum from the brain that forms the posterior pituitary

Rathke's pouch

Specific diverticulum from the mouth that forms the anterior pituitary

Process of development of pituitary

Brain infundibulum bulges downward and Rathke's pouch bulges upwards to meet

Stalk of Rathke's pouch regresses, leaving it stranded with infundibulum

Rathke's pouch connects with the posterior lobe, posterior lobe hugs Rathke's pouch

Both lobes become surrounded with growing sphenoid bone (sella turcica)

Sella turcica

"Turkish saddle"

Saddle shaped depression in the sphenoid bone that protects the pituitary

Hypophysectomy

Removal of pituitary

Endoscope inserted through nose or upper lip

Done to treat cancer due to out of control hormones

Primordial Germ Cells (PGC)

Common origins of spermatozoa and oocytes (primordial follicles

PGC migration

PGC migrate from base of hindgut (near yolk sac) by ameboid movement

PGC seek out and colonize the genital/gonadal ridge (area along dorsal body wall)

Arrival of PGC initiates formation of bipotential gonads

What do PGC do once they get to the gonadal ridge?

Divide and make more

Stimulate genital ridge growth, forming primitive sex cords that will become gonads (seminiferous tubules or cortex of ovary)

Close to kidneys

Bipotential gonads

Indeterminate preliminary gonads that have yet to differentiate towards ovaries/testis

How do PGC know where to go?

Chemical signals

Chemoattraction and repulsion create gradients that repel PGC from hindgut and attracts to gonadal ridge

Development of urogenital system

Mesonephros

Primitive kidneys

Metanephros

What eventually becomes the real kidneys

Mesonephric duct

Wolffian duct

Forms the male tract

Connected to metanephros and bipotential gonads

Paramesonephric duct

Mullerian duct

Forms the female tract

Anti mullerian hormone = mullerian duct regresses

Not connected to bipotential gonads - hovers over like infundibulum hover over ovaries

How is SRY created?

Synthesized by sex cords carrying a y chromosome

Starts being created once PGC arrive

Effect of SRY on reproductive development

Testes form in the presence of SRY

Ovaries form in the absence of SRY

How does SRY develop the male tract?

SRY causes testis development

Sertoli cells in the testis make AMH (anti mullerian hormone)

AMH prompts leydig cells to make testosterone

Testosterone and AMH cause the mullerian duct to degenerate, causing the male duct system to develop

What would happen if SRY was deleted?

Female reproductive tract would develop

Female tract with XY chromosomes

What would happen if SRY was added to an X chromosome in an XX individual?

Male reproductive tract would develop

Male tract with XX chromosomes

What would happen if someone was XY but had androgen receptor insensitivity

AMH is still generated causing degeneration of paramesonephric duct

External genitalia would not develop, causing a mismatch of external and internal gonads

Where do the testis develop?

Next to kidneys near ribs

Outside the peritoneal cavity

What are the phases of the descent of the testis

1. Trans-abdominal phase - growth of fetal body pushes testis against peritoneum

2. Inguinal-scrotal phase - rapid growth of gubernaculum

3. Gubernaculum regression - testes pass through inguinal canal

Gubernaculum

Ligamentous cord attached to bottom of testis

Trans abdominal phase of testis descent

Growth of fetal body pushes against testis

Testis are outside peritoneum and become enveloped

Dependent on INSL3

Inguinal-Scrotal Phase of testis descent

Rapid growth of gubernaculum mechanically pulls testis towards the inguinal canal

Gubernaculum Regression Phase of testis descent

The regression of the gubernaculum pulls testes through the inguinal canal

Peritoneum pinches off around testicular artery, basically surrounding it in its own tube of peritoneum