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Veterans Affairs Medical Center (H.F.S.H., W.G., J.E.O., L.M.P.), East Orange, New Jersey 07019; and Department of Surgery, Section of Urology (H.F.S.H., M.-T.L.) and Neuroscience (J.E.O.) University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey 07103
Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats.
Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 2530%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.
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