On the descent of the epididymo-testicular unit, cryptorchidism, and prevention of infertility

Abstract

This comprehensive review provides in-depth coverage of progress made in understanding the molecular mechanisms underlying cryptorchidism, a frequent pathology first described in about 1786 by John Hunter. The first part focuses on the physiology, embryology, and histology of epididymo-testicular descent. In the last 20 years epididymo-testicular descent has become the victim of schematic drawings with an unjustified rejection of valid histological data. This part also includes discussion on the roles of gonadotropin-releasing hormone, fibroblast growth factors, Müllerian inhibiting substance, androgens, inhibin B, and insulin-like 3 in epididymo-testicular descent. The second part addresses the etiology and histology of cryptorchidism as well as the importance of mini-puberty for normal fertility development. A critical view is presented on current clinical guidelines that recommend early orchidopexy alone as the best possible treatment. Finally, by combining classical physiological information and the output of cutting-edge genomics data into a complete picture the importance of hormonal treatment in preventing cryptorchidism-induced infertility is underscored.

Keywords: Cryptorchidism; Epididymo-testicular descent; GnRHa-treatment; Infertility; Mini-puberty; RNA sequencing.

Fig. 1

10-week-old male fetus with testis (T) located intra-abdominally and intraperitoneally. Testis is connected to Wolffian duct (VD) with the testicular ligament (TL) while the gubernaculum, which is divided into two parts, inserts proximally into the Wolffian duct via an intraabdominal part (AG) and an inguinal part (G). Internal abdominal oblique muscle (IO) and fascia of extra-abdominal oblique muscle (EO and arrow) as well as fascia from transversal abdominal muscle (T and arrow) are labeled

Fig. 2

Four-month-old fetus with intra-abdominal and intra-peritoneal testis (T) with meso-testis at the dorsal abdominal wall below the kidney (K). Processus vaginalis starts to develop (*). The topographical relation of gubernaculum and developing Wolffian duct is identical as in Fig. 1. However, in parallel to the new formation of processus vaginalis the inguinal part of the gubernaculum also enlarges

Fig. 3

Sagittal cut through epididymo-testicular unit of a five-month-old fetus. Testis (T) is surrounded by head (HE), body (BE) and tail (TL) of the epididymis. The testicular ligament, the connection between testis and the tail of the epididymis (TL) becomes narrow. The inguinal parts of gelatinous gubernaculum (G) show cremaster muscle fibers at its periphery. Processus vaginalis (*) and internal oblique muscle (IO) are indicated

Fig. 4

Topography of epididymo-testicular unit presented in serial sagittal sections (from distal to proximal) of 6-month-old fetus. The gubernaculum (G) is a thick cord composed of loose mesenchymal tissue with irregularly arrayed thin cremaster muscle fibers at periphery. At its proximal end, (AG) the gubernaculum is connected to the tail of the epididymis (TE, arrow). Short testicular ligament (TL) is connecting the tail of the epididymis to the testis (T). Notice; gubernaculum is never directly attached to the testis but always to the tail of the epididymis. [Deep inguinal ring and processus vaginalis (asterisk), transversus muscle fascia (T, arrow), internal oblique muscle fascia (IO), external oblique muscle fascia (EO), body of the epididymis (BE), deferent duct (VD)]

Fig. 5

Topography of epididymo-testicular unit presented in serial sagittal sections (from distal to proximal) of 6-month-old fetus. The gubernaculum (G) is a thick cord composed of loose mesenchymal tissue with irregularly arrayed thin cremaster muscle fibers at periphery. At its proximal end, (AG) the gubernaculum is connected to the tail of the epididymis (TE, arrow). Short testicular ligament (TL) is connecting the tail of the epididymis to the testis (T). Notice; gubernaculum is never directly attached to the testis but always to the tail of the epididymis. [Deep inguinal ring and processus vaginalis (asterisk), transversus muscle fascia (T, arrow), internal oblique muscle fascia (IO), external oblique muscle fascia (EO), body of the epididymis (BE), deferent duct (VD)]

Fig. 6

Topography of epididymo-testicular unit presented in serial sagittal sections (from distal to proximal) of 6-month-old fetus. The gubernaculum (G) is a thick cord composed of loose mesenchymal tissue with irregularly arrayed thin cremaster muscle fibers at periphery. At its proximal end, (AG) the gubernaculum is connected to the tail of the epididymis (TE, arrow). Short testicular ligament (TL) is connecting the tail of the epididymis to the testis (T). Notice; gubernaculum is never directly attached to the testis but always to the tail of the epididymis. [Deep inguinal ring and processus vaginalis (asterisk), transversus muscle fascia (T, arrow), internal oblique muscle fascia (IO), external oblique muscle fascia (EO), body of the epididymis (BE), deferent duct (VD)]

Fig. 7

Topography of epididymo-testicular unit presented in serial sagittal sections (from distal to proximal) of 6-month-old fetus. The gubernaculum (G) is a thick cord composed of loose mesenchymal tissue with irregularly arrayed thin cremaster muscle fibers at periphery. At its proximal end, (AG) the gubernaculum is connected to the tail of the epididymis (TE, arrow). Short testicular ligament (TL) is connecting the tail of the epididymis to the testis (T). Notice; gubernaculum is never directly attached to the testis but always to the tail of the epididymis. [Deep inguinal ring and processus vaginalis (asterisk), transversus muscle fascia (T, arrow), internal oblique muscle fascia (IO), external oblique muscle fascia (EO), body of the epididymis (BE), deferent duct (VD)]

Fig. 8

Topography of epididymo-testicular unit presented in serial sagittal sections (from distal to proximal) of 6-month-old fetus. The gubernaculum (G) is a thick cord composed of loose mesenchymal tissue with irregularly arrayed thin cremaster muscle fibers at periphery. At its proximal end, (AG) the gubernaculum is connected to the tail of the epididymis (TE, arrow). Short testicular ligament (TL) is connecting the tail of the epididymis to the testis (T). Notice; gubernaculum is never directly attached to the testis but always to the tail of the epididymis. [Deep inguinal ring and processus vaginalis (asterisk), transversus muscle fascia (T, arrow), internal oblique muscle fascia (IO), external oblique muscle fascia (EO), body of the epididymis (BE), deferent duct (VD)]

Fig. 9

24 weeks old fetus, sagittal sections displaying topographical relations between processus vaginalis, testis, epididymis, ligamentum testis and gubernaculum

Fig. 10

Sagittal section of a newborn’s body and the tail of epididymis and their topographical relation to processus vaginalis (*), testis (T), ligamentum testis and gubernaculum. The gubernaculum is virtually inexistent (G) and the testicular ligament (TL) undergoes the process of retroperitonealization and becomes a part of the scrotal wall. [Histological sections are personal material obtained from Töndery-Collection Institute of Anatomy Zürich]

Fig. 11

Synopsis of testicular descent from Barteczko and Jakob [3]. Gubernaculum is sketched to be connected to the caudal testicular pole during the entire descent.(arrow). This however could not be confirmed by precise histological pictures. Furthermore, topographical relation of developing epididymis and testis are incorrectly pictured in that epididymis and particular its tail appears small and atrophied (Fat arrow)

Fig. 12

Dominant role of Ad spermatogonia in predicting fertility outcome is outlined. + + / − −; strong correlation; +/− significant correlation. Ad CDT (scrotal testis) is the best predictor of future fertility. Ad UDT (undescended testis) is a decisive factor for supporting an FSH negative feedback mechanism. GCT UDT (total germ cell count in undescended testis) and GCT CDT (total germ cell count in scrotal testis) have no direct influence either on the sperm count or on the plasma FSH level