Spermatogenesis

Hormonal Regulation of Spermatogenesis

hormones within the pituitary, luteinizing hor-

Spermatogenesis is highly sensitive to fluctua-

mone (LH) and follicle stimulating hormone

(FSH). While high pulse rate of GnRH release (1

tions in hormones. Testosterone is required in

impulse per 1 h) results in the production of

high local concentrations to maintain sper-

LH, low pulse rate of GnRH release (1 impulse

matogenesis. This is achieved via binding of

per 2 h) results in the production of FSH.Within

testosterone by androgen-binding protein (ABP)

the testis, LH causes synthesis of testosterone

present in seminiferous tubules. Hormonal reg-

by intertubular Leydig cells, which negatively

ulation of spermatogenesis is organized as con-

influences hormone release in hypothalamus

trol circuit with a negative feedback mechanism

and pituitary. By contrast, FSH acts on intratu-

involving hypothalamus, pituitary, and testis

bular Sertoli cells. It induces the production of

(Fig. 4.8). Specific neurons of the hypothalamus

ABP by means of which testosterone can pass

synthesize gonadotropin releasing hormone

the Sertoli–Sertoli junctional complexes, as well

(GnRH), which induces the production of two

as the production of activin and inhibin by

Hypothalamus

GnRH

Pituitary

Testosterone

LH

FSH Inhibin Activin

Testosterone

Leydig cell

Sertoli cell

Testosterone + ABP

Figure 4.8. hormonal regulation of

Germ cell

spermatogenesis.

62

Practical Urology: EssEntial PrinciPlEs and PracticE

Sertoli cells, which influences hormone release

Blood Vessels, Lymphatic Drainage, and

both in hypothalamus and pituitary.

Nerves

The testicular artery originates from the abdom-

Genetic Regulation of Spermatogenesis

inal aorta. Due to the descensus testis, the

testicular artery is located within the retroperi-

The differentiation of spermatogonial stem cells

toneum. It crosses the psoas muscle and the ure-

ter, passes the canalis inguinalis and enters the

into fertile sperm requires stringent temporal

spermatic cord where it makes anastomoses

and stage-specific gene expression.This becomes

with the arteria ductus deferentis and the arte-

evident when studying the sequential nucleo-

ria cremasterica. The arteria testicularis passes

protein expression in developing germ cells

the testis dorsal and enters the tunica albuginea

resulting in histone to protamine exchange in

from ventral basal to ventral apical branching

haploid spermatids.4 Although, in man, replace-

into the septula testis. From the rete testis, arte-

ment of histones is only about 85% complete,5

riae recurrentes supply the tubuli seminiferi

protamines represent the predominant nucleo-

(Fig. 4.9). This special schedule of arterial sup-

proteins of elongated spermatids and mature

ply is the rationale for the operation approach to

spermatozoa.

retrieve testicular material coming always rom

Protamines bind lengthwise within the minor

the free rim of the testicle.

groove of the DNA double helix with their cen-

The testicular artery is surrounded by the

tral polyarginine

segment cross-linking and

plexus pampiniformis. Veins merge to the vena

neutralizing the

phosphodiester backbone of

testicularis dextra which opens into the vena

the DNA. These DNA-protamine complexes of

cava inferior and the vena testicularis sinistra

one DNA strand fit exactly into the major

which opens into the vena renalis sinistra.

grooves of a parallel DNA strand and are packed

side by side in a linear array within the sperm

A. testicularis

nucleus.6 In addition to DNA binding,protamine

molecules interact with other protamine mole-

A.ductus deferentis

cules by forming disulfide bonds between

cysteine residues, thereby facilitating DNA com-

A.cremasterica

paction. Ward7 performed a model for the pack-

ing of the entire haploid genome into the sperm

nucleus in which DNA loop domains are packed

as doughnuts attached to the sperm nuclear

matrix. Protamine bound DNA is coiled into

large concentric circles that collapse into a

doughnut in which the DNA-protamine com-

plexes are tightly packed together by van der

Waal’s forces.

Protamine-DNA interactions result in chro-

matin condensation causing cessation of tran-

scription in elongating spermatids. This occurs

at a time when many proteins need to be synthe-

sized and assembled for the complete condensa-

tion of the chromatin, the development of the

acrosome, and the formation of the flagellum.

Therefore, it is evident that precise temporal reg-

ulation of gene expression via transcriptional

and translational control mechanisms is of fun-

damental importance to ensure complete differ-

entiation of round spermatids into mature

spermatozoa.4

Figure 4.9. Blood supply of testicle.