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Epididymal compounds and their influence on the metabolism and survival of spermatozoa.

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American Journal of Primatology 1:143 - 155 (1981)
Epididymal Compounds and Their Influence on the
Metabolism and Survival of Spermatozoa
I.G. WHITE
Department of Veterinary Physiology,Uniuersity of Sydney, N.S.W., 2006,Australia
Epididymal fluid, which is derived from testicular fluid, contains several unusual compounds. Little information is available on the composition of the
testicular fluid of primates, but the fluid of the ram, bull, boar, and rat contains
high concentrations of inositol and certain amino acids.
Analyses have been made of epididymal fluid collected from the cauda
epididymis of the Rhesus monkey and several nonprimate species (e.g., ram,
bull, dog, stallion, rabbit, guinea pig, rat, and hamster), but similar information
on the human is lacking. Cauda epididymal fluid appears to be similar in
composition from one mammalian species to another. However, the epididymal
plasma differs considerably from blood, lymph, and other extracellular fluids.
The environment of spermatozoa in the epididymis is, therefore, highly specialized, and presumably in some way contributes to the prolonged survival of
spermatozoa in this organ, and provides substrates for the metabolism of the
spermatozoa.
The chief characteristics of the cauda epididymal plasma are the low concentration of inorganic ions and the high levels of several unusual organic constituents namely, glycerylphosphorylcholine, carnitine, sialic acid, amino acids,
glycosidases, and phosphatases.
At least one antifertility compound, namely, orally administered achlorohydrin, appears to be concentrated in the epididymis. Studies on laboratory animals, domestic species, and man, suggest that it inhibits enzymes of the
glycyolytic pathway in spermatozoa, and this may be the basis for its antifertility activity.
Key words: testis, epididymis, spermatozoa, monkey, ram, bull,
glycerylphosphorylcholine,carnitine, a-chlorohydrin
INTRODUCTION
The primary function of the epididymis is to bring about the ripening or maturation of
the spermatozoa and to provide a receptacle for their storage. In the epididymis, spermatozoa are bathed in the fluid or epididymal plasma that fills the lumen of the duct.
Epididymal fluid contains several unusual compounds and is derived from the rete testis
fluid, which is modified by the absorptive and secretory activity of the epididymal
epithelium.
Received December 11, 1980; accepted December 12, 1980
Address reprint requests to I.G. White, Department of Veterinary Physiology, University of Sydney, N.S.W., 2006,
Australia.
0275-2565/81/0102-0143$04.00 0 1981 Alan R. Liss. Inc.
144
White
In this paper, the chemical composition of the testicular and epididymal fluid of mammalian species is briefly reviewed. Where possible, information on primates has been
included, but the great gaps in knowledge for such species points to the need for increased
research in this area.
TESTICULAR FLUID
Spermatozoa are swept out ofthe seminiferous tubules, through the rete testis, and into
the epididymis in fluid that is believed to be actively secreted by the Sertoli cells. Studies
on a number of species, but only to a very limited extent on nonhuman primates and not
yet on man, show that the composition is different from that of blood and lymph draining
the testis due to a blood-testis barrier. The selectively permeable barrier restricts the
passage of some substances from the blood into the testicular fluid, even though they pass
into the lymph. Although some work has been done in this area using the rat and ram as
models Isetchell & Waites, 1975;Waites, 19761,amore exhaustive study ofthe passage of
pharmacologically active substances from the blood into the testicular fluid is clearly
desirable. Such a study, especially if conducted in primates, could suggest new approaches to arresting the development of human spermatozoa in the epididymis.
Information on the composition of the testicular fluid first came from analyses of
material obtained from slaughtered bulls and rams by severing the junction of the testis
and epididymis. Since then, a more elegant technique has been evolved which enables the
rete testis to be cannulated and fluid to be obtained from living animals, eg, ram, bull,
rabbit, rat, and even monkey. [White, 1973; Setchell, 1974; Setchell & Waites, 1975;
Voglmayr, 1975; Waites, 19761.
Testicular fluid has a low spermatozoa1concentration and the composition is shown in
Table I. Although the data available for primates is very limited, there is a considerable
amount of work on other mammalian species. Perhaps the most striking feature of the
testicular fluid is the low glucose and high inositol content.
TABLE I. Chemical Composition of Testicular Fluid
Constituent
Sodium
Potassium
Calcium
Magnesium
Chloride
Bicarbonate
Protein
Urea
Alanine (mM)
Glycine (mM)
Glutamic acid (mM)
Aspartic acid (mM)
Serine (mM)
Glucose
Inositol
Lactic acid
Ascorbic acid
Glycerylphosphorylcholine
Testosterone
(p.g/100 ml)
Monkey
313
29
Ham
27 1
48
4.1
0.8
454
49
280
28
0.33
1.87
2.03
0.33
0.36
<2
131
5.9
3.0
80
0.3-3.0
2.8-8.0
Bull
Boar
Rat
308
35
1.9
1.0
433
42
540-1300
34
1.04
1.09
2.19
0.43
0.73
<2
347
21
4.8
329
54
476
497
128
510
165
0.48
1.19
1.96
0.29
<2
126
6.6
2.8
9-19
2.3
Values are mgilO0 ml unless otherwise stated. Data are from White, 1979.
52
0.90
1.87
0.08
0.17
(2
32-88
2.6
Epididymal Compounds and Effect on Sperm
145
Glucose is not, therefore, available as a n energy source to spermatozoa during the whole
of the 2 or 3 hr that it takes them to pass from the seminiferous tubules to the head of the
epididymis. Inositol does not stimulate the respiration of washed sperm [Voglmayr &
White, 19711and is not utilized to any extent as a substrate [Voglmayr & Amman, 19731.
Lactic acid, however, would be available to spermatozoa from the testicular fluid, if the
oxygen tension were sufficiently high for its oxidation, as it is readily oxidized by
testicular spermatozoa in vitro.
As might be expected from the existence of a blood-testis barrier, the total protein
content of the testicular fluid is less than that of the blood plasma and their nature is
different [Waites, 19761. Three interesting proteins have been described in ram testicular fluid. The androgen-binding protein (ABP)of ram testicular fluid is produced by the
Sertoli cells, and may be concerned with the transport of androgens to the caput
epididymis [Hansson et al, 19761. “Inhibin” if absorbed from the caput epididymidis,
might regulate spermatogenesis via suppression of FSH production by the anterior
pituitary. Testicular fluid of the ram also contains a peptide inhibitor of sperm acrosin
which may inactivate any proteases that leak out of the acrosome.
A number of amino acids, eg, glutamic acid, glycine, alanine, aspartic acid, and lysine,
occur in a higher concentration in testicular fluid than in the blood plasma of the bull,
ram, and rat due presumably to synthesis within the seminiferous tubules. The slow rate
of oxidation indicates that amino acids are unlikely to form a significant metabolic fuel
for spermatozoa in the epididymis.
Testosterone, dehydroepiandrosterone, and also estrogens have been found in the rete
testis fluid of the monkey, bull, ram, boar, rat, and rabbit in concentrations a t least as
high as in the peripheral blood plasma [Waites, 19761.Transfer studies indicate that the
steroids arise from the interstitial cells; the seminiferous tubules are exposed to a high
concentration of testosterone, which plays a part in the maintenance of spermatogenesis
and perhaps also directly influences spermatozoa in the epididymis.
EPIDIDYMAL FLUID
The fluid in the lumen of the epididymis constitutes the environment not only for the
maturation but also for the storage of spermatozoa, and it is not unreasonable to suppose
that the composition of the fluid may play some part in both processes [Bedford, 1975;
Glover, 1976; Orgebin-Crist et al, 19761. Better understanding of the mechanisms involved in maintaining the epididymal environment may provide means of manipulating
it to the disadvantage of the sperm. Information on the secretory function of the
epididymis would seem particularly relevant to the possibility of introducing systematically or locally administered spermicides into the lumen. One such antifertility agent,
u-chlorohydrin, is concentrated in the cauda epididymis and will there attack the stored
sperm [Waites, 19761.
Fluid has been obtained from the epididymis of animals after slaughter and fluid
collected from fistula or cannula in the vas deferens of live animals. The volume of fluid
flowing through the epididymis of the ram is less than 1mliday, which contrasts sharply
with a volume of40 mliday produced from a cannula inserted into the rete testis. Clearly,
much of the fluid produced by the testis is absorbed in the efferent ducts and caput
epididymis and leads to a much greater concentration of spermatozoa in the tail. It must
be remembered, of course, that the cells ofthe epididymis also secrete substances into the
lumen so that the composition of the fluid a t any point along the duct will represent a
balance between absorption ofwater and sodium chloride and secretion of more complex
organic components.
Analyses have been made of epididymal fluid collected from the cauda epididymis of the
Rhesus monkey and several nonprimate species (eg, ram, bull, dog, stallion, rabbit,
guinea pig, rat, and hamster), but similar extensive published information on the human
is lacking (Table 11). The data ofJones [1978] would indicate that cauda epididymal fluid
10.5 t 0.2
-
-
18.2 ? 1.5
49.2 2 5.2
4.0 i 0.8
Monkey
Nonenzymatic (mg%1
7366 i 1321
Total protein
Glycerylphosphoryl2396 ? 187
choline
1290 ? 134
Carnitine
349 ? 27.8
Total sialic acid
Urea nitrogen
Ammonia
238 t 46
Total phosphorus
Inorganic
5.2 ? 0.9
phosphorus
Ionic (MEQ)
Na+
KMg+
Ca2Zn2+
C1-
Constituent
13.2 i- 2.5
459
9.5
46.3
2.4
1.1
18.1
3168 ? 634
27.9 t 3.2
221
1274 2
175 t
213 T
17.2 ?
4.8 ?
368 t
i
41.3 f 1.3
32.1 ? 1.6
2.4 2 0.8
1.1 i 0.2
0.1 t 0.2
12.0 ? 0.1
Stallion
2677 i 344
313 ? 30.5
179 t 55.6
17.3 i 0.9
4.5 ? 0.6
339 ? 31
2743
22.1 i 3.8
23.7 ? 3.0
0.6 ? 0.2
0.8 t 0.2
0.05 -+ 0.1
9.4 ? 0.3
Ram
6.7
2
0.5
1320 ? 310
98 t 4.2
105 t 9.2
16.2 k 1.5
3.5 ? 0.4
393 2 12.9
2483 t 152
30.1 i 2.5
36.3 T 1.1
1.5 2 0.1
1.8 t 0.2
0.2 t 0.0
7.8 ? 0.3
Boar
22.4 -+ 1.8
924 t 239
320 t 73.3
265 2 12.3
9.3 2 0.2
2.5 ? 0.2
590 ? 43
3016 i 335
22.0 i 2.8
37.6 ? 0.4
2.2 t 0.2
1.7 i 0.1
0.1 2 0.0
15.5 ? 1.6
Dog
?
1.8
0.1
t 0.1
t 0.8
2
t 2.1
-c 0.8
12.2 -e 1.1
1609 I 266
671 t 93.1
157 2 24.7
23.4 t 2.9
2.1 ? 0.4
231 L 6.8
4440 t- 38
20.2
23.1
14.4
0.94
0.21
9.8
Rabbit
1.5
t 1.2
i 0.1
i 0.1
i 0.1
t 1.3
i
16.8 ?1.3
1406 2 176
1085 t 108
234 i 37.1
26.4 i 0.7
1.4 i 0.1
333 2 7.2
4200 i 154
17.0
18.2
4.4
0.2
0.05
10.0
Guinea-pig
29.5
976
1318
142
14.0
1.7
190
4093
20.0
-
24.3
43.1
2.6
0.22
Rat
TABLE 11. The Concentration of Some Ionic, Enzymatic, and Nonenzymatic Constituents of Epididymal Plasma From the Cauda
Epididymis (Jones, 1978)
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Epididymal Compounds and Effect on Sperm
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148
White
is essentially similar in composition from one mammalian species to another, although
there may be differences in the concentrations of some constituents. However, the
epididymal plasma differs considerably from blood, lymph, and other extracellular
fluids. The environment of spermatozoa in the epididymis is, therefore, highly specialized, and presumably in some way contributes to the prolonged survival of spermatozoa
in this organ, and provides substrates for the metabolism of the spermatozoa.
The chief characteristics of the cauda epididymal plasma are the low concentration of
inorganic ions and the high levels of several unusual organic constituents, namely,
glycerylphosphylcholine,carnitine, sialic acid, hypotaurine, glycosidases, and phosphatases. The concentrations of Na' ions are about 20.0 mEqiliter which is much less
than in blood plasma [Jones, 19781.The levels ofK+ions generally equal or exceed that of
Na+; in the monkey, in particular, K ' levels are twice those of Na' .
It is generally agreed that pH values vary along the length of the epididymis, but are
usually within the range of 6.5 to 7.0 [Levine & Marsh, 1971; Jones & Glover, 1973;
Wales et al, 1966; Levine & Kelly, 19783, although occasionally higher values have been
obtained [White & Wales, 19611.
Glycerylphosphorylcholine(GPC), Glycerol, and a-Chlorohydrin
One of the quantitatively most important constitutents of epididymal fluid is the
andogen-dependent glycerylphosphorylcholine.GPC is a specific secretory product of the
epididymis. It is found principally in the caput [Wallace et al, 19661, and very high
concentrations accumulate in cauda epididymal plasma. That it is, in fact, the epididymis
and not the testis that is responsible for the production of GPC is shown by the progressive increase in its concentration in fluids taken from the rete testis, the head and tail of
the epididymis, and the vas deferens of the ram and bull [White, 19731. Concurrent
analyses indicate that the concentration of sodium and chloride ions decreases, while the
potassium concentration remains about the same. It would appear, therefore, that at
least some sodium chloride may be replaced by GPC as fluid passes from the rete testis
through to the vas deferens, and the osmotic pressure of the lumen fluid tends to be
maintained, in the face of loss of sodium chloride, by the secretion of GPC from the
epithelial cells lining the lumen.
When labeled 32Pis injected into guinea pigs, rats, and rabbits, it is incorporated into the
GPC of the epididymis within several hours. Phospholipid has been suggested as a
possible precursor of GPC; the specific activity of phospholipid was always less than GPC
in experiments on the rabbit, however, and this suggests a pathway of GPC synthesis in
the epididymis that may not proceed via lecithin [White, 19723.
The epididymal epithelium oxidizes lipids and some GPC may also accummulate in the
epididymal lumen as a result of this activity and perhaps to a lesser extent as the result of
oxidation of phospholipids by sperm. Clearly, as fluid passes through the epididymis,
tremendous quantities of GPC are added to it and this raises the question of the function,
if any, of GPC in that organ, and a possible interrelation with the orally active male
antifertility agent, a-chlorohydrin, which is concentrated in the epididymis and bears a
striking structural resemblance to GPC.
It is possible that GPC might be in part responsible for the fact that spermatozoa
can survive for long periods in the epididymis; GPC might even play some part in
the maturation process that occurs as spermatozoa pass through the epididymis. GPC,
as such, is not metabolized by spermatozoa, but the female tract secretions of
many species possess a diesterase capable of splitting off the choline leaving phosphorylglycerol, which spermatozoa can metabolize [White & Wallace, 19611. The
physiological significance of this reaction is uncertain, but it is at least theoretically
possible that GPC can act as a substrate for sperm metabolism in the female genital tract
although not in the epididymis. Spermatozoa can metabolize glycerol [Mann & Whate,
Epididymal Compounds and Effect on Sperm
149
1957; White, 19571, and Brooks 119791 has suggested that it might serve as an energy
substrate for spermatozoa in the epididymis, although reliable estimates of glycerol in
the epididymis are not yet available.
Glycerol could pass to the epididymal lumen, either as a result of lipid metabolism in the
epididymal epithelium, or by transport from the blood stream in a manner analagous to
the accumulation of radioactivity by the epididymis following the administration of
radioactive a-chlorohydrin [Crabo & Appelgren, 1972; Edwards et al, 19751. Glycerol
enters the glycolytic pathway of the spermatozoon through a phosphorylation step
followed by oxidization to dihydroxyacetone phosphate catalyzed by mitochondrial
glycerol phosphate dehydrogenase.
Studies on ram spermatozoa indicate that the glycerol analogue, a-chlorohydrin exerts
its detrimental effect on spermatozoa by blocking the glycolytic pathway a t the glyceraldhyde phosphate stage.
However, a-chlorohydrin does not itself appear to be the actual active compound
causing disruption of sperm metabolism. Preincubation of sperm with a-chlorohydrin is
required before inhibition of the metabolism of glycerol or glucose occurs [Edwards et al,
19761 and a-chlorohydrin does not itself inhibit the glycolytic enzymes in ram sperm
[Mohri et al, 1975; Brown-Woodman et al, 19781. It is probably a metabolic product of
a-chlorohydrin that inhibits the enzymes ofthe glycolytic sequence in sperm [Mohri et al,
19751 and, in particular, glyceraldehyde phosphate dehydrogenase.
Carnitine
The rat cauda epididymis has the highest carnitine and acetylcarnitine content of any
tissue [Marquis & Fritz, 19651.Carnitine has been found in epididymal plasma of the bull
[Casillas, 19731, in the epididymal tissue of monkeys and boars [Casillas, 19721, and in
fluid from the epididymis and seminal vesicles of humans [Lewin, 19761. Accumulation
of carnitine by the epididymis is similar to GPC in being dependent on this androgen.
However, carnitine is not synthesized by the epididymis[Casillas & Erickson, 1975al but
is concentrated from the blood, so that in humans, for example, the epididymal carnitine
concentration is 10-50 times higher than blood plasma [Bohner et al, 19741.
The regions involved in carnitine transport from the blood are the distal caput, corpus,
and proximal cauda with the consequence that the concentration of carnitine progressively increases throughout the length of the epididymis [Brooks et al, 19741. Its high
concentration must contribute to the osmotic pressure of the fluid and at least partly
redress the loss of sodium chloride in the proximal region of the duct.
The role of carnitine as a carrier of fatty acids across mitochondrial membranes is well
established in other tissues and acetylcarnitine may serve as an energy reservoir and
buffer against rapid changes in the concentration of acetyl-CoA in spermatozoa. It has
also been suggested that the maturation of sperm in the epididymis may be related to
accumulation of carnitine in the sperm during epididymal transit. Due to membrane
changes during maturation, only caput spermatozoa are permeable to carnitine [Casillas, 19731, although both cauda and caput spermatozoa are apparently permeable to
acetylcarnitine.
It is now clear that the acetylation state of carnitine can be profoundly influenced by the
presence of exogenous substrates [Casillas & Erickson, 1975b; Milkowski et al, 1976;
Van Dop et al, 19771 and that acetylcarnitine can act as a ready source of oxidizable
acetyl units for spermatozoa [Storey & Keyhani, 1974;Hutson et al, 1977a1,in addition to
serving as a buffer to acetylCoA levels.
It is possible that acetylcarnitine represents an important energy store in spermatozoa
particularly as bovine epididymal spermatozoa incubated with substrates, eg, fructose,
glucose, pyruvate, lactate, and acetate, have a higher acetylcarnitine content than
spermatozoa incubated without substrate [Casillas & Erickson, 1975131.
150
White
Inositol
The epididymis contains significant amounts of inositol [Eisenberg & Bolden, 19641,
and although it is carried to the epididymis in the rete testis fluid [Setchell et al, 19683,
inositol may also be accumulated from the blood stream [Lewin et al, 19761.
Lactic Acid
Lactic acid occurs in epididymal plasma as well as testicular fluid [Scott et al, 1963b;
Setchell et al, 1969; Setchell, 1970; White, 19731, and the presence of this lactic acid
probably accounts for the slightly acidic nature of caudal plasma. Values for lactic acid
were substantially higher in epididymal plasma which had been collected from rabbits
postmortem compared with material obtained from anaesthetized animals [Jones, 19781,
presumably due to tissue anoxia.
The production of lactate by the rat epididymis would seem sufficient to meet the needs
of spermatozoa. However, in addition to such lactate resulting from epididymal
glycolysis, it might also be transported from the blood stream to the epididymal lumen.
The oxidation of lactate by spermatozoa requires oxygen and from the measurements of
Cross and Silver [1962],epididymal tissue appearsto be reasonably aerobic; this has been
confirmed by direct intraluminal measurements of oxygen tension by Free et a1 [ 19761.
Amino Acids
A number of amino acids occur in cauda epididymal fluid in concentrations greater than
in rete testis fluid, due presumably to selective resorption of fluid in the head of the
epididymis.
Quantitatively, glutamate (10-30 mM) is the most important amino acid in epididymal
plasma of the ram and bull [Setchell et al, 1967; Sexton et al, 1971;Johnson et al, 1972;
Brown-Woodman & White, 19741. In boar and rabbit epididymal plasma hypotaurine (50
mM) is the principal amino acid.
Some of the 12 or so amino acids present in epididymal plasma [Neumark & Schindler,
19671 are potential metabolites for both the spermatozoa and epididymal epithelium,
although they do not increase the oxygen uptake of the washed spermatozoa and are only
oxidized a t a slow rate.
Lipids
Fatty acids could be made available for sperm metabolism as a result of metabolic
activity of the epididymal epithelium or by the transport of fatty acids from the blood
stream into the epididymal lumen. Free fatty acids could not, however, be detected in
epididymal plasma from the ram, boar, or rabbit [Jones, 19783, but palmitic, stearic, and
oleic acids have been found in cauda epididymal plasma of the rat at about five times the
concentration of the blood plasma [Brooks et al, 19741.
In addition to substrate supplied from the epididymal plasma, it is possible that the
spermatozoa themselves are endowed with intracellular fuel. The traditional view is that
fatty acids derived from the side chains of the phospholipid components of the spermatozoa constitute this substrate during epididymal transit and storage.
Decreases in the total phospholipid content of spermatozoa during epididymal transit
have been reported for the ram [Scott et al, 19671, bull [Poulos et al, 19731, boar [Grogan
et al, 19661, rat [Terner et al, 19751,and monkey [Arora et al, 19751.The total loss of lipid
in bovine sperm during epididymal transit would be sufficient to support sperm respiration for 28 hr. However, as epididymal transit takes about 14 days, it is clear that
endogenous lipid is not sufficient on its own to maintain sperm metabolism. Some
workers have even questioned the ability of a t least ejaculated ram and human spermatozoa to utilize endogenous phospholipids [Poulos & White, 1973; Darin-Bennett,
Poulos 8.z White, 19731.
Epididymal Compounds and Effect on Sperm
151
Steroids
Several steroids occur in epididymal as well as testicular fluid. Ganjam and Amann
[ 1973, 19761 report the presence of high concentrations of testosterone, dihydrotestosterone, 3-P-androstanediol, dehyroepiandiosterone, and progesterone in cauda
epididymal fluid of the bull.
The spermatozoa bind, in a nonsaturable fashion, various steroids with different
affinities [Amann & Hammerstedt, 19761, but there are few, if any, specific, saturable,
high-affinity, steroid-binding sites on bull spermatozoa. Spermatozoa can also interconvert certain steroids to some extent [Hammerstedt & Amann, 19761. However, in vitro,
very high concentrations of steroids are required to change the metabolic parameters of
spermatozoa, and even then the effects are not very spectacular [Hammerstedt &
Amann, 19761.
Enzymes
The presence of a wide variety of hydrolytic enzymes in epididymal plasma of the
Rhesus monkey and all species investigated might at first sight seem paradoxical, since
these enzymes might be expected to have an adverse effect on the survival of spermatoma. It has been suggested that in the normal animal they may help remove dead or
effete spermatozoa from the epididymis, thereby ensuring that only normal fertile
spermatozoa are ejaculated [Mann, 1964; Waldschmidt et al, 1964; Mennela & Jones,
19771.They may also have some role during sperm maturation, such as modification of
membrane-bound surface glycoproteins.
Sialic Acid and Glycoprotein
Another androgen-dependent constituent of the cauda epididymis is the amino-sugar
sialic acid which has been shown to occur in particularly high concentrations bound to
protein in the cauda epididymis of the rat. The degree of polymerization of these
sialomucoproteins influences the phy sico-chemical properties of the epididymal plasma,
particularly its viscosity, and they may serve as lubricants to assist in sperm transport
by reducing the friction between the densely packed sperm in the cauda [Hamilton,
19751.
There have been at least two recent reports of an interaction between the glycoprotein
in epididymal fluid and epididymal sperm suggesting that glycoproteinsmay be involved
in sperm maturation. Thus Brandt et a1 [19781 have shown that motility may be induced
in immotile sperm taken from the caput epididymis of the bull by exposing them to a
mixture of cyclic AMP phosphodiesterase inhibitor, eg, theophylline and a glycoprotein
factor in the seminal plasma. Zimmermann et a1 L19791working with the boar have found
that as sperm mature in the epididymis they become less permeable to Na+ and K+ and
that the factor responsible is probably a glycoprotein in the cauda plasma.
SURVIVAL OF SPERM IN EPIDIDYMIS
Experiments on the ligated epididymis of the rabbit, bull, and ram show that conditions
in the epididymis are peculiarly conducive to the survival of spermatozoa. The ability of
spermatozoa to survive for long periods in the epididymis may be linked with either
physical or chemical conditions in the organ, and it is generally believed that spermatozoa are immotile, or nearly so, in the epididymis and that their metabolism is in a
quiescent state.
Although there is no direct evidence that sperm are, in fact, in an inactive state in the
cauda epididymis, there has been no lack of theories as to why this may be so. These
involve (1)low oxygen tension, (2) lack of substrate, (3) low pH, (4) high carbon dioxide
tension, (5)high potassium, (6) hypertonity, (7) dense packing of the sperm, and (8) the
presence of a metabolic regulator in the sperm.
152
White
The question of what constitutes the substrate for the metabolism of spermatozoa stored
in the epididymis is an intriguing one and might constitute a point of attack for decreasing their viability. Conditions in the tubules are probably aerobic, at least immediately
next to the epithelium and even if, as is generally supposed, spermatozoa are in a
quiescent state, at least some basal metabolism might be expected to maintain the
integrity of the cells, The relatively high concentration of lactic acid and acetyl carnitine
in the epididymal lumen may provide substrate for spermatozoal metabolism. Although
GPC occurs in tremendous quantities in the luminal fluid, it cannot be used directly by
spermatozoa; glutamic acid is only oxidized extremely slowly and there is little fructose,
glucose, or acetate present. If, of course, there were a constant interchange between
epididymal fluid and the blood, a substrate such as glucose could still be of importance in
the economy of the spermatozoa, despite a low level at any one time. Some recent studies
on the ram and rabbit are of interest in this regard, in that they show that intravenously
infused 14C glucose appears in the fluid of the cauda epididymis.
CONCLUSIONS
Detailed knowledge of the nature of testicular fluid, which forms the basis of
epididymal fluid, is available for the ram, bull, boar, and rat but information on
primates is very meager.
More information is available on the composition of epididymal fluid of the rhesus
monkey, but there are still many gaps in knowledge compared to the situation for
domestic species.
The significance of the high concentration of unusual compounds eg, glycerylphosphorylcholine, carnitine, amino acids, and inositol, in epididymal fluid is unknown.
The fact that a-chlorohydrin is concentrated in the epididymis and inhibits the
metabolism of sperm gives hope that a satisfactory orally active male contraceptive
may eventually be found that interferes with sperm in the epididymis.
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