Effect of Vasectomy on P34H Messenger Ribonucleic Acid Expression along the Human Excurrent Duct: A Reflection on the Function of the Human Epididymis

Abstract

Sperm surface proteins involved in fertilization can be added or modified during epididymal transit. P34H, a human epididymal-sperm protein, appears on the sperm acrosomal cap in the distal caput-proximal corpus epididymis. In previous studies, it was shown that P34H is present on spermatozoa in men of proven fertility, is absent in 50% of men presenting with idiopathic infertility, and that a high proportion of men with normospermic vasovasectomy produce spermatozoa deficient in this sperm surface protein. P34H mRNA was expressed in the principal cells of the epididymis of normal men, predominantly in the corpus region. Recently, results coming from the assisted reproductive technologies have questioned the importance of the human epididymis in sperm maturation. In order to understand the effect of obstruction on the physiological state of the human epididymis and its function in sperm maturation, we have analyzed the expression of P34H mRNA at the level of the vas deferens and along the epididymis of normal and vasectomized men. In situ hybridization experiments showed that obstruction of the vas deferens alters the pattern of P34H mRNA expression compared with the tract of normal tissues. The P34H transcript was detected in the proximal caput epididymis of vasectomized men at a much higher intensity than that observed in the same region of normal tissues, being restricted to the principal cells of the epididymal epithelium. Compared with the normal duct, the lumen of vasectomized men was distended throughout the duct and the height of the epithelium was maximal in the caput. P34H mRNA was detectable in vas deferens, was not affected by vasectomy, and a 912-base pair P34H transcript was restricted to the epithelial cells of the vas deferens. Thus, using P34H as a marker, these results show that vasectomy alters the pattern of gene expression along the human epididymis, and suggest that the vas deferens can be a major contributor to sperm maturation in certain situations.

Effects of Vasectomy on Gene Expression Profiling along the Human Epididymis1

“…In adults, the height of the epididymal epithelium is proportional to protein synthesis [63]. In humans, the height of the epididymal epithelium is maximal in the distal caputproximal corpus, while the thickness of the epithelium is more uniform along the excurrent duct after vasectomy [18]. This may influence the segment specificity of gene expression following vasectomy.…”

“…Three other donors of 26-50 yr of age, with no medical pathologies that could affect reproductive function, were used as normal controls [24]. Tissues were obtained and processed as previously described [17,18]. Briefly, epididymides were collected under optimum conditions while artificial circulation was maintained to preserve organs assigned for transplantation and processed within 3 h following surgical retrieval.…”

“…DCXR is thus a marker of epididymal sperm maturation in men, and can be used to identify epididymal dysfunction involved in male fertility [13,15,16]. Under vasectomy, the gene encoding DCXR is not expressed by the corpus epididymidis as in normal men [17], but in the proximal caput [18]. We reported that a high proportion of normospermic vasovasostomized men produces spermatozoa deficient in DCXR protein [19].…”

Epididymal P34H protein deficiency in men evaluated for infertility

“…The anatomical sequelae of a shift of the expression of P34H from the corpus to the proximal caput epididymis, leading to compromised epididymal sperm maturation, may play an essential role in this phenomenon (24). The same mechanism, possibly triggered by traumatic or inflammatory epididymal injury and resulting in (7) Note: All data are n (%).…”

Proteomic Profiling of Regionalized Proteins in Rat Epididymis Indicates Consistency between Specialized Distribution and Protein Functions

“…12 In many cases epididymal dysfunction has been shown to be related to abnormal protein expression. 13,14 Thus, when identified, such proteins may be targets for diagnosis and treatment of human infertility. On the other hand, they may also be potential targets in the design of specific contraceptive medicines.…”