Figure 1. Testis anatomy and selective MGCA sequestration.

(A) Sperm production occurs in cycles (different colors) longitudinally along seminiferous tubules (SFT) (ia, ib). Mature sperm are transported to the vas deferens (v) via the rete testis (ii), ductus efferentes (iii), and epididymis (iv). (B) Seminiferous tubules, visualized by IF on Scx-GFP mouse testes with GFP⁺ Sertoli cells (green) and LDH3 (red), contain LDH3^– spermatogonia (white arrows) and LDH3⁺ spermatocytes (yellow arrows). Insert: occludin⁺ Sertoli cell barriers (red) located between adjacent Sertoli cells (green). I/T, interstitial space. Original magnification, ×500; ×800 (insert). (C) A seminiferous tubule segment with 2 Sertoli cells (light green) depicts the complete MGCA sequestration paradigm. Sertoli cells support spermatogenesis (steps i–iv) and spermiation (steps v–ix). Spermatogonia (i) traverse the Sertoli cell barriers to become MGCA⁺ spermatocytes (ii, pink), then round (iii) and elongating (iv) spermatids. At spermiation, redundant cytoplasm (yellow) and plasma membrane (black) are partially detached from elongated spermatids (v) to form residual bodies (vi) destined for degradation inside Sertoli cells (vii), and retained as cytoplasmic droplets (viii) on mature sperm (ix). The interstitial space contains spermatogonia, basal lamina, peritubular cells (not shown), Leydig cells, macrophages, and afferent lymphatic vessels (not shown). Sertoli cells and Sertoli cell barriers (purple) sequester all MGCA⁺ meiotic germ cells inside seminiferous tubules. (D) The new selective MGCA sequestration paradigm supported by our study is shown. Tolerogenic NS-MGCA are located in residual bodies and not removed by Sertoli cells. They enter the basal Sertoli cell cytoplasm and egress into the interstitial space. S-MGCA, including those in the sperm acrosome (green crescent), absent from residual bodies, are nontolerogenic. Note that some, but not all, residual bodies are destroyed by the Sertoli cells (vii).