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From the * Veterans Affairs Medical Center, East
Orange, New Jersey; and the Department of Surgery Division of
Urology,
Neuroscience, and
Obstetrics/Gynecology, UMD-New Jersey Medical
School, Newark, New Jersey.
| Correspondence to: H. F. S. Huang, Department of Surgery Section of Urology, UMD-New Jersey Medical School, 185 S Orange Avenue, Newark, NJ 07103 (e-mail: huanghf{at}umdnj.edu). |
| Received for publication May 15, 2003; accepted for publication August 6, 2003. |
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Abstract |
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Key words: Sertoli cells, CREM, sperm
Testosterone (T) alone, when administered in sufficient amount, is capable of maintaining or restoring qualitatively complete spermatogenesis in hypophysectomized animals (Huang et al, 1987; Santulli et al, 1990) and has been proven effective in preserving spermatogenesis in animals subjected to cytotoxic insults (Delic et al, 1986; Pogach et al, 1988; Meistrich et al, 1999). Our previous studies demonstrated that regression of spermatogenesis after SCI could also be partially prevented by exogenous T (Huang et al, 1999). This result suggested the feasibility of using exogenous T or a related agent to preserve spermatogenesis, and thereby sperm production, in SCI men. To facilitate such application, the current experiment examined whether spermatogenesis in the rat could respond to exogenous T in normal fashions after SCI. Because of the importance of CREM in postmeiotic differentiation (Sassone-Corsi, 1998), we also examined the effects of exogenous T on the expression and cellular distribution of CREM.
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Materials and Methods |
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Immediately after the SCI surgery, the rats were given subcutaneous implants of various lengths (1, 2, 3, 5, 10, and 20 cm) of T-filled Silastic capsules (TCs, inner diameter = 3.35 mm, outer diameter = 4.65 mm, Dow Corning International, Corning, NY) (Huang et al, 1987) in the flank region. Implantation of TCs resulted in stable serum T levels that were correlated with TC lengths (Huang and Boccabella, 1988; Huang et al, 1991). Sham control animals received 5-cm empty capsules. The animals were killed by decapitation 8 weeks later, and trunk blood was collected for measurement of serum hormones. One half of 1 testis from each rat was fixed in Bouin solution and processed for histology. The remaining tissues were frozen immediately in isohexane immersed in a mixture of methanol and dry ice and then stored at -80°C. In a follow-up experiment, sham control and additional SCI rats were given TC implants of 1, 2, 3, 5, or 10 cm immediately after the surgery and were killed 8 weeks later.
Quantification of Sonication-Resistant Sperm Head
Approximately 500 mg of testicular tissue from each rat was sonicated in 2
mL phosphate-buffered saline (PBS). The sonication-resistant sperm heads were
counted with a hemocytometer. Results were expressed as sperm head number per
gram of tissue.
Sperm Motility
One caudal epididymides from each rat was immersed in 2 mL 37°C PBS
containing 1% bovine serum albumin immediately after it was excised.
Subsequently, epididymal sperm were released by puncturing the epididymal duct
at 20-30 locations with a 19-gauge needle. The sperm suspensions were kept at
37°C for 10-15 minutes. A drop of sperm suspension was then placed on a
prewarmed hemocytometer and examined. Sperm in 10-20 microscopic fields were
videotaped, and sperm motility was later determined. A sperm was considered
"motile" when it did not remain at the same location during the
5-10-second taping time of each field.
Hormone Measurement
Serum FSH, LH, and testosterone and testicular testosterone (ITT)
concentrations were determined by radioimmunoassay as previously described
(Huang et al, 1995).
Immunostaining of CREM
Five-micron-thick sections of testicular tissues fixed in Bouin solution
were deparaffinized in xylene, rehydrated through graded ethanol, and boiled
in 0.01 M citrate buffer (pH 6.0) for 10-15 minutes. After washing in PBS (2
x 5 minutes), the sections were incubated with 1.5% hydrogen peroxide
for 10 minutes, washed twice in distilled water followed by 2 changes of PBS
(5 minutes each), and blocked in 4% normal goat serum in PBS containing 0.01%
Tween 20 for 20 minutes. After 2 washes in PBS, the sections were subsequently
incubated with polyclonal anti-CREM antibody (Santa Cruz Biotechnology, Inc.,
Santa Cruz, Calif, 1:300 dilution in blocking solution) at 4°C overnight.
For negative control, CREM antibody was incubated with fivefold excess of
purified antigen at 4°C overnight and diluted to 1:300 in blocking
solution before use. The sections were subsequently washed in 2 changes of
PBS, incubated with Biotin-labeled anti-rabbit IgG (Sigma Chemical, St. Louis,
Mo, 1:2000) for 30 minutes, and washed with PBS. The sections were then
incubated with Vectastain Elite ABC reagent (Vector Laboratories, Burlingame,
Calif) for 30 minutes, washed in 2 changes of PBS, and visualized after adding
stable 3-3'-diaminobenzidine tetrahydrochloride solution (Research
Genetics, Huntsville, Ala). After counterstaining with fast green, the slides
were dehydrated in graded ethanol solution, cleared in xylene, and
covered.
Western Blotting of CREM
For Western blotting of CREM, 300-500 mg of testicular tissue was
solublized in lysis buffer (1% Nonidet P-40, 0.5% sodium deoxycholate, and
0.1% sodium dodecyl sulfate [SDS] in PBS) in the presence of protease
inhibitors (Phenylmethylsulfonyl fluoride and aprotinin). Polyacrylamide gel
electrophoresis and Western blotting were performed according to the
procedures described previously (Molina et
al, 1993). The anti-CREM polyclonal antibody recognizes all CREM
gene products and was used at 1:1000 dilution.
Statistics
All data were evaluated to determine that they were normally distributed,
and they were analyzed with analyses of variance with TC dose as the
independent variable. When the treatment effects were significant (P
< .05), planned a priori comparisons were made using Dunn's tests to
determine the statistical significance of differences among treatment
groups.
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Results |
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The testis weights of untreated SCI rats were reduced by 20%, but the decrease was not statistical significant. Implantation of 1-10-cm TCs resulted in dose-dependent, biphasic changes in testis weights in sham control rats, reaching a nadir in those that received 2-cm TCs (P < .01). Although implantation of 1-cm TCs did not affect the testis weights of SCI rats (P > .1), testis weights of those SCI rats that received 2- or 3-cm TC implants were reduced by >60% compared to untreated SCI rats (P < .01; Figure 2A). Testis weights of SCI rats given 5-cm or longer TC implants rebounded and were greater than those of the 2- or 3-cm groups (P < .05), but the difference remained statistically significant when compared to those of untreated SCI rats (P < .01).
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Spermatogenesis
Of the 8 untreated SCI rats, 5 had persisting spermatogenesis in 50%-90% of
the tubules examined. However, impaired spermatogenesis, ranging from partial
regression of the epithelium to the absence of proliferating spermatogonia,
were seen in all rats (Figure
3B). Of the 7 SCI rats given 1-cm TC implants, 1 had a totally
regressed seminiferous epithelium in more than 95% of the tubular cross
sections. Qualitatively normal spermatogenesis, except for delayed
spermiation, was seen in more than 95% of the tubules in the remaining 6 rats.
On the other hand, regression of the seminiferous epithelium, ranging from
persistence of proliferating spermatogonia to the absence of all spermatogenic
cells, including proliferating spermatogonia, was seen in 80%-100% of the
tubular cross sections in 5 of the 7 SCI rats that received 2-cm TC implants
(Figure 3C). In the other 2
rats, regression of spermatogenesis was also seen in more than 50% of the
tubules, but spermatocytes or young spermatids remained in some tubules.
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Of the 5 SCI rats that received 3-cm TC implants, 1 had a regressed epithelium in all tubules. In the remaining 4, incomplete spermatogenesis, characterized by the presence of spermatogonia, spermatocytes, and young spermatids, but without elongated spermatids, was seen in more than 95% of the tubules (Figure 3D). Complete spermatogenesis, characterized by the presence of mature spermatids at the lumenal edges of stages VII-VIII epithelia, was maintained in 4 of 7, 2 of 4, and 5 of 5 SCI rats that received TC implants of 5, 10, and 20 cm, respectively (Figure 3E and F). Spermatogenesis was partially maintained or regressed in the remaining rats from these groups. Spermatogenesis in sham control rats given various lengths of TC implants in the follow-up experiments (not shown) was comparable to those reported previously (Huang and Boccabella, 1988; Huang et al, 1991).
Sperm Head Number
Figure 2B shows that the
sonication-resistant sperm head in SCI rats was reduced by 20% in those given
1-cm TCs and was undetectable in those given 2-cm TCs (P < .001).
It reappeared in the testes of those rats given 3-cm TCs and rebounded to the
level of untreated rats in rats given 10-cm TCs (P < .01).
Sperm Motility
Percent motility of sperm recovered from the caudal epididymides of SCI
rats was significantly lower than that of sham control rats (P <
.05; Figure 2C). Implantation
of 10- or 20-cm TCs resulted in a slight decrease of sperm motility in sham
control rats (P < .05). Despite the presence of residual sperm in
those SCI rats that received 2- or 3-cm TC implants, and significant number of
sperm in those that received 5-cm TCs, none of these sperm were motile
(Figure 2C). Although a large
number of sperm was present in the caudal epididymides of those SCI rats given
10- or 20-cm TC implants, only less than 20% of these sperm were motile
(P < .05).
Western Blotting of CREM
Western blotting of testicular lysates revealed a general decrease in
levels of CREM
(the activator isoform, see "Discussion") in
the testes of SCI rats (Figure
4A). This decrease was not affected by implantation of 1-cm TCs
but was further suppressed in those SCI rats that received 2-5-cm TC implants.
CREM levels in the SCI rats that received 10- or 20-cm TC implants were
not different from those of untreated SCI rats. Implantation of TCs of
different lengths in sham control rats did not affect CREM significantly
(Figure 4B).
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Cellular Distribution of CREM
In sham control rats, CREM immunostaining was localized primarily in
maturing pachytene spermatocytes and young spermatids; presence of CREM in
spermatogonia and prepachytene spermatocytes was rare
(Figure 5A). In untreated SCI
rats, CREM was also detected in young spermatids, but the intensity of CREM
immunostaining was less pronounced (Figure
5B). Implantation of 1-cm TCs resulted in a further decrease in
CREM staining in spermatids (not shown). Although CREM was also detected in
some young spermatids in those SCI rats receiving 3-cm TC implants, it
appeared primarily in spermatogonia and prepachytene spermatocytes in 3 of 5
of the rats in this dose group (Figure 5C
and D). Of note, in spite of persistence of complete
spermatogenesis, CREM was not detected in young spermatids in those SCI rats
given 5-cm TC implants (Figure
5E). In 5 of the 6 rats in this group, CREM was present in
spermatogonia and primary spermatocytes, including preleptotene spermatocytes,
in most of the tubules (Figure
5F). These results were confirmed 2-3 times with slides from each
animal immunostained at different dates. CREM reappeared in young spermatids
in most of the tubules of SCI rats given 10- or 20-cm TC implants, regardless
of the status of spermatogenesis (Figure
5G). However, young spermatocytes in many of the tubules,
specifically those with partially regressed epithelia, also contained
immunoactive CREM. Immunostaining of CREM in the testes of sham control rats
given different lengths of TC implants in the follow-up experiment revealed
normal cellular distribution of CREM
(Figure 5H), despite variations
in staining intensity. We also retrospectively examined CREM cellular
distribution in archived testicular tissues fixed in Bouin solution of intact
and hypophysectomized rats given various lengths of TC implants from previous
studies (Huang and Boccabella,
1988; Huang et al,
1991). CREM was distributed normally in maturing spermatocytes and
young spermatids in all tissues, regardless of the status of spermatogenesis
and variations in the intensity of immunostaining (not shown). Specificity was
demonstrated by the absence of CREM immunostaining when the sections were
stained with antigen preadsorbed antiserum
(Figure 5I).
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Discussion |
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The effects of increasing doses of exogenous T on serum LH, FSH, and testicular T and biphasic changes in spermatogenesis in SCI rats were consistent with those seen in intact rats (Zirkin et al, 1989; Santulli et al, 1990; Huang et al, 1991). However, dose effects of T on spermatogenesis seen in SCI rats were different from those seen in intact rats. Specifically, although implantation of 1-cm TCs resulted in a 40% reduction of testis weight and incomplete spermatogenesis in non-SCI intact rats (Huang and Boccabella, 1988), identical treatment maintained testis weight and qualitatively complete spermatogenesis in SCI rats. Total regression of the seminiferous epithelium in SCI rats that received 2-cm TC implants, characterized by the absence of proliferating spermatogonia in many tubular cross sections, also differed from their sham control counterpart. These changes resembled those that occurred in chronic SCI rats (Huang et al, 1995) and after testicular denervation (Chow et al, 2000) and were far more severe than that occurred in chronic hypophysectomized rats (Huang et al, 1987) and in SCI rats that received 3-cm TC implants and had nearly identical testicular T levels. The putative neurogenic mechanisms contributing to the loss of proliferating spermatogonia after SCI and testicular denervation must have been exaggerated specifically by the 2-cm TC regimen. Although such an effect was overcome by higher doses of exogenous T (3-20-cm TC implants), failure to maintain complete spermatogenesis in SCI rats given 3-cm TC implants also differed from their sham control rat counterparts. Such differences cannot be ascribed to hormone status, suggesting that local factors might be involved in neural-endocrine interactions in the control of spermatogenesis. Maintenance of qualitatively complete spermatogenesis and relatively normal sperm motility in SCI rats that received 1 cm-TC implants nevertheless suggests potential applicability of specific low doses of exogenous T in preservation of spermatogenesis and sperm function in SCI men.
A decrease in sperm motility in untreated SCI rats was consistent with that in SCI men. Such effects could be attributed to abnormal sperm transport, maturation in the epididymis, or both (Linsenmeyer et al, 1999) as a result of impaired epididymal function after denervation (Billups et al, 1990). Although sperm motility in SCI rats was not affected by the 1-cm TC implant, it was totally eliminated in those rats that received 5-cm TC implants but rebounded slightly in those that received 10- or 20-cm TC implants. Because epididymal function of these SCI rats would have been better stimulated than in those that received 1-cm TC implants because of the elevated serum T level, the loss and rebound of sperm motility in SCI rats that received 5-20-cm TC implants might reflect functional status of the sperm motile apparatus. In addition, because sperm motility also was decreased in the sham control rats that received 5- or 10-cm TC implants, a difference in the metabolic states of sperm secondary to changes in epididymal function under different serum T conditions might also contribute to differences in sperm motility.
Testosterone modulates spermatogenesis through its effects on Sertoli cells. These effects were initiated by the binding of T to, and activation of, androgen receptors (AR) that transactivate androgen-dependent genes to induce changes in Sertoli cell functions (Zhou et al, 1994). Such effects thus mediate the effects of androgen on spermatogenesis. However, presence of AR and androgen-binding protein (ABP) in spermatogenic cells (Vornberger et al, 1994; Joseph et al, 1997), stimulation of protein synthesis in spermatocytes by the T/ABP complex (Gerard, 1995), and presence of a hormone-responsive element (HRE) in the promoter of genes that encode germ cell-specific proteins (Bonny et al, 1998; Ha et al, 1997) suggest that T might also affect spermatogenic cells directly. In addition, recent studies have demonstrated that cAMP signaling might also mediate some effect of androgen, especially in those cells lacking functional AR (Heinline and Chang, 2002).
CREM is a nuclear transcription factor that modulates the function of
cAMP-responsive genes (Foulkes et al,
1991; Habener et al,
1996). Alternative gene splicing results in different CREM
isoforms that either activate or repress the function of cAMP
(Foulkes et al, 1991). In
prepubertal animals, CREM repressor isoforms (CREM 
and ß) were
detected in spermatogonia, early meiotic cells, or both
(Foulkes et al, 1992). In adult
testes, the activator isoform (CREM) was detected mainly in maturing
spermatocytes and young spermatid and was a functional switch for postmeiotic
germ cell differentiation (Foulkes et al,
1992; Sassone-Corsi,
1998). Modulation of the expression of CREM by FSH and T
(Foulkes et al, 1993;
West et al, 1994) suggests its
role in mediating the effects of hormones on spermatogenesis. Recently, we
reported changes in the short-term effects of FSH and T on testicular CREM
transcripts and transcripts for Sertoli and germ cell-specific proteins
encoded by cAMP-responsive genes in SCI rats
(Huang et al, 2003a). Current
observation of abnormal cellular localization of CREM in SCI rats that
received 3- and 5-cm TC implants further illustrated changes in the timing of
CREM translation during spermatogenic differentiation. Decreased localization
of CREM in spermatids in these SCI rats was consistent with a reduction of
CREM protein in their testicular tissues. Because such effects were only seen
in SCI rats that received 3- or 5-cm TC implants, and not in their sham
control counterparts, they were most likely related to changes in cellular
function attributable to a specific neural-endocrine interaction. These
findings were consistent with changes in hormonal regulations of cAMP
signaling in testicular cells after SCI. Precocious expression of CREM in
spermatogonia and young spermatocytes has also been observed in acute SCI rats
following cord contusion (Huang et al,
2003b). Such changes could disturb cAMP signaling in spermatogenic
cells; impede normal spermatogenesis; and result in reduced sperm count or
production of sperm with abnormal functions or both. Persistence of CREM in
spermatids in SCI rats given 1-cm TCs and its reappearance in spermatids in
those rats that were given 10- and 20-cm TC implants and had qualitatively
complete spermatogenesis support our postulate. Further studies with reverse
transcription PCR techniques (Peri et al,
1998) to characterize properties of CREM in isolated spermatogenic
cells of SCI rats could provide new insights into the functional roles of
different CREM isoforms in mediating the neural-endocrine interaction in the
control of spermatogenesis. In this regard, premature expression of Pm-1 has
been linked to spermatogenic arrest (Lee
et al, 1995), and reduced CREM expression has been found in human
testes with spermatid maturation arrest
(Peri et al, 1998; Steger et al, 1999).
The results of this study demonstrate changes in the effects of exogenous T on spermatogenesis in the rat after SCI. Preservation of spermatogenesis and sperm motility in SCI rats that received 1-cm TC implants suggests potential efficacy of low doses of exogenous T in the maintenance of sperm production and function in SCI men. These effects were associated with changes in the expression of testicular CREM and its distribution in spermatogenic cells. These results support the notion that altered cAMP signaling and its regulation in testicular cells might be mediating the effects of SCI on spermatogenesis. Such changes might affect timely and sequential progression of spermatogenesis and might contribute to the production of sperm with abnormal morphology and function after SCI.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Bonny C, Cooker LA, Goldberg E. Deoxyribonucleic acid-protein
interactions and expression of the human testis-specific lactate dehydrogenase
promoter: transcription factor Sp1 plays a major role. Biol
Reprod. 1998;58:754-759.
Brackett NL, Lynne CM, Weizman MS, Bloch WE, Abae M. Endocrine profiles and semen quality of spinal cord injured men. J Urol. 1994;151:114-119.[Medline]
Chow S-H, Giglio W, Anesetti R, Ottenseller JE, Pogach LM, Huang HFS. The effects of testicular denervation on spermatogenesis in the Sprague Dawley rat. Neuroendocrinology. 2000; 72:37-45.[Medline]
Delic JI, Bush C, Peckham MJ. Protection from procarbazine-induced damage of spermatogenesis in rat by androgen. Cancer Res. 1986;46:1909-1914.
Foulkes NS, Borrelli E, Sassone-Corsi P. CREM gene: use of alternative DNA binding domains generates multiple antagonists of cAMP-induced transcription. Cell. 1991; 64:739-749.[Medline]
Foulkes NS, Mellstrom B, Benusiglio E, Sassone-Corsi P. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature. 1992; 355:80-84.[Medline]
Foulkes NS, Scholtter F, Pevet P, Sassone-Corsi P. Pituitary hormone FSH directs the CREM functional switch during spermatogenesis. Nature. 1993;362:264-267.[Medline]
Gerard A. Endocytosis of androgen binding protein (ABP) by spermatogenic cells. J Steroid Biochem Mol Biol. 1995; 53:533-542.[Medline]
Ha H, van Wijne AJ, Hecht NB. Tissue-specific protein-DNA interactions of the mouse protamine 2 gene promoter. J Cell Biochem. 1997;64:94-105.[Medline]
Habener JF, Miller CP, Vallejo M. cAMP-dependent regulation of gene transcription by cAMP response element-binding protein and cAMP response element modulator. Vitam Horm. 1996; 51:1-57.
Heinline UI, Chang C. The role of androgen receptors and androgen
binding proteins in nongenomic androgen actions. Mol
Endocrinol. 2002;16:2181-2187.
Hirsch IH, McCue P, Allen J, Lee J, Staas WE. Quantitative testicular biopsy in spinal cord injured men: comparison to fertile controls. J Urol. 1991;146:337-341.[Medline]
Huang HFS, Boccabella AV. Dissociation of the quantitative and qualitative effects of the suppression of testicular testosterone upon spermatogenesis. Acta Endocrinol. 1988; 118:209-217.
Huang HFS, Li M-T, Giglio W, Anesetti R, Ottenweller JE, Pogach P.
The detrimental effects of spinal cord injury on spermatogenesis in the rat is
partially reversed by testosterone, but enhanced by follicle-stimulating
hormone. Endocrinology. 1999; 140:1349-1355.
Huang HFS, Li MT, Giglio, Anesetti R, Pogach LM, Ottenweller JE. Alteration of cAMP signaling in rat testicular cells after spinal cord injury. J Spinal Cord Med. 2003a; 26:69-78.[Medline]
Huang HFS, Li MT, Wang S, Wang G, Ottenweller JE. Spinal cord
contusion impairs sperm motility in the rat without disrupting
spermatogenesis. J Androl. 2003b; 24:371-380.
Huang HFS, Linsenmeyer TA, Li MT, Giglio W, Anesetti R, von Hagen
J, Ottenweller JE, Pogach L. Acute effects of spinal cord injury on the
pituitary-testicular hormone axis and Sertoli cell functions: a time course
study. J Androl. 1995; 16:148-157.
Huang HFS, Marshall GR, Rosenberg R, Nieschlag E. Restoration of spermatogenesis by high levels of testosterone in hypophysectomized rats after long term regression. Acta Endocrinol. 1987; 116:433-444.
Huang HFS, Pogach L, Nathan, Giglio W, Seebode JJ. Synergistic effects of FSH and testosterone upon the maintenance of spermiogenesis in hypophysectomized rats. Relationship with the androgen binding protein status. Endocrinology. 1991; 128:3152-3161.[Abstract]
Joseph DR, O'Brien DA, Sullivan PM, Becchis M, Tsuruta JK, Petrusz P. Over expression of androgen-binding protein/sex hormone binding globulin in male transgenic mice: tissue distribution and phenotypic disorders. Biol Reprod. 1997; 56:21-32.[Abstract]
Lee K, Haugen HS, Clegg CH, Braun RE. Premature translation of
protamin-1 mRNA cause precocious nuclear condensation and arrests spermatid
differentiation in mice. Proc Natl Acad Sci USA. 1995; 92:12451-12455.
Linsenmeyer TA, Ottenweller JE, D'Imperio JS, Pogach LM, Huang HFS. Epididymal sperm transport in normal and recent spinal cord injured Sprague Dawley rats. J Spinal Cord Med. 1999; 22:102-106.[Medline]
Linsenmeyer TA, Perkash I. Infertility in men with spinal cord injury. Arch Phys Med Rehab. 1991; 72:747-754.[Medline]
Linsenmeyer TA, Pogach LM, Ottenweller JE, Huang HFS. Spermatogenesis and the pituitary testicular hormone axis in rats during the acute phase of spinal cord injury. J Urol. 1994; 152:1302-1307.[Medline]
Means AR, Fakunding JL, Huckins C, Tindall DJ, Vitale R. Follicle stimulating hormone, the Sertoli cells and spermatogenesis. Recent Prog Horm Res. 1976;32:477-572.
Meistrich ML, Wilson G, Huhtaniemi I. Hormonal treatment after
cytotoxic therapy stimulates recovery of spermatogenesis. Cancer
Res. 1999;59:3557-3560.
Molina CA, Foulkes NS, Lalli E, Sassone-Corsi P. Inducibility and negative auto-regulation of CREM: an alternative promoter directs the expression of ICER, an early responsive repressor. Cell. 1993;75:875-886.[Medline]
Peri A, Krausz C, Cioppi F, Granchi S, Forti G, Francavilla S,
Serio M. Cyclic adenosine 3',5'-monophosphate-responsive element
modulator gene expression in germ cells of normo- and oligoazospermic men.
J Clin Endocrinol Metab. 1998; 83:3722-3726.
Pogach L, Lee Y, Gould S, Giglio W, Huang HFS. Partial prevention
of procarbazine induced germinal cell aplasia in rats by sequential GnRH
antagonist and testosterone administration. Cancer
Res. 1988;48:4354-4360.
Santulli R, Sprando RL, Awoniyi CA, Ewing LL, Zirkin BR. To what extent can spermatogenesis be maintained in the hypophysectomized adult rat testis with exogenous testosterone? Endocrinology. 1990; 126:95-102.[Abstract]
Sassone-Corsi P. CREM: a master-switch governing male germ cell differentiation and apoptosis. Cell Dev Biol. 1998; 9:475-482.
Steger K, Klonisch T, Gavenis K, et al. Round spermatids show
normal testis-specific H1t but reduced cAMP-responsive element modulator and
transition protein expression in men with round spermatid maturation arrest.
J Androl. 1999;20:747-754.
Vornberger W, Prins G, Musto NA, Suarez-Quian CA. Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis. Endocrinology. 1994; 134:2307-2316.[Abstract]
West AP, Sharpe RM, Saunders PTK. Differential regulation of cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein and cAMP response element modulator messenger ribonucleic acid transcripts by follicle-stimulating hormone and androgen in the adult rat testis. Biol Reprod. 1994; 50:869-881.[Abstract]
Zhou ZX, Wong C-I, Sar M, Wilson EM. The androgen receptor: an overview. Recent Prog Horm Res. 1994; 49:249-274.
Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989; 124:3043-3049.[Abstract]
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