The Human Blood-Testis Barrier in Impaired Spermatogenesis

Abstract

The aim of this study was to explore the competence of the blood-testis barrier (BTB) using electron opaque tracers in diverse human testicular pathologies associated with Sertoli cell only syndrome. Two groups of patients were studied: (1) those with complete depletion (absence) of germ cells, and (2) those with severe germ cell depletion but with some germ cells left in the seminiferous epithelium. The first situation was associated with cryptorchidism with absence of germinal cells, idiopathic cases of aplasia of germ cells, peritumoral areas surrounding small seminomas where the seminiferous tubules were observed to contain a predominant population of Sertoli cells, or long estrogen treatment. The second was found also in cryptorchidism with early germ cells, idiopathic azoospermia, and oligospermia associated with sterility. In the first situation, seminiferous tubules lacked lumen and Sertoli cells had immature morphological characteristics, i.e., oval nuclei with smooth profiles, even heterochromatin distribution and a single, small nucleolus. Inter-Sertoli tight junctions were tortuous, interrupted, and mostly perpendicular to the basal lamina. Lanthanum hydroxide or nickel nitrate permeated most of the inter-Sertoli spaces, indicating disruption of the BTB. In the second situation, seminiferous tubules had a lumen, and Sertoli cells exhibited a mature appearance with large tripartite nucleoli and irregular, highly infolded nucle-olemma. Only spermatogonia or primary spermatocytes showing diverse degrees of cell involution were found. Numerous inter-Sertoli tight junctions, uninterrupted and parallel to the basal lamina, stopped the electron opaque intercellular tracers close to it; this meant the assembly of a competent BTB. Therefore, a close correlation was found between morphological parameters of Sertoli cell maturity, including their tight junction organization, and BTB integrity.

A study to assess the assembly of a functional blood-testis barrier in developing rat testes

“…35 In summary, we have shown that an intact BTB is relatively established by 20 dpp during postnatal development in rats, however, a fully functioning BTB is not assembled until 25 dpp. Figure 7 summarized the key findings in this report.…”

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

“…32,79 In the testis, earlier morphological studies described severe disorganization of gap junction structure in men with impaired spermatogenesis. [80][81][82][83][84] More recently, it has been reported that Cx43 mRNA and protein are absent within seminiferous tubules but are still present in Leydig cells in azoospermic patients with Sertoly cell only (SCO) syndrome. [85][86][87] However, no testicular alteration was reported in men with Cx gene mutations.…”

The Blood-Testis Barrier and Its Implications for Male Contraception

“…This concept is critical in light of earlier observations that androgens promote (Janecki et al, 1992;Chung and Cheng, 2001;Meng et al, 2005;Wang et al, 2006;Siu et al, 2009b;McCabe et al, 2010;Xiao et al, 2011) and estrogens perturb (Cavicchia et al, 1996;Li et al, 2009dLi et al, , 2010 Sertoli cell BTB integrity in in vitro and in vivo studies. However, as briefly summarized and discussed herein, studies investigating the transport of steroids using drug transporters are limited to sulfated estrogens, DHEA, and others; further investigation must assess whether estradiol-17␤, testosterone, and/or dihydrotestosterone can penetrate the BTB equally well using drug pumps.…”