Testicular histopathology and its association with germ cell numbers, serum concentrations of reproductive hormones, and semen quality.

Background: It is well-established that spermatogenesis, semen quality, and reproductive hormones are interlinked. It is, however, less well-described how various specific testicular histopathologies are linked to reproductive hormones and semen quality.

Objectives: To describe the detailed relationship between specific testicular histopathologies and the serum concentrations of reproductive hormones and semen quality.

Materials and methods: Descriptive histological patterns on testicular biopsies from 4245 patients referred for andrological workup in our clinic between 1990 and 2022 were grouped according to a published histological coding system: (1) complete spermatogenesis (completeSPG, n = 3171), (2) reduced spermatogenesis (reducedSPG, n = 657), (3) heterogeneous (hetArrest, n = 226), and (4) homogeneous (homArrest, n = 191) spermatogenic arrest at the spermatocyte or spermatid stage. As a proxy for the number of spermatogonia, spermatocytes, and spermatids, immunohistochemical staining for MAGE-A4, PIWIL1, and TNP1 were quantified on a representative set of biopsies (n = 100). Serum concentrations of FSH, LH, T, SHBG, and inhibin B (n = 1813) and semen parameters (n = 833) were available.

Results: Compared with the completeSPG group, the number of spermatogonia was only reduced in the hetArrest group, while the number of spermatocytes and spermatids were lower in all groups. All groups had significantly higher FSH and LH and lower T, free T, and inhibin B concentrations when compared with the completeSPG group, except for the homArrest group, where inhibin B was unaffected. The hetArrest group had the lowest number of germ cells, the most pronounced change in reproductive hormones, and the lowest sperm counts. We found a strong correlation between the number of germ cells present and the corresponding serum concentrations of FSH, LH, T, and inhibin B.

Discussion and conclusions: A histopathological pattern of heterogeneous spermatogenic arrest is associated with a more severe phenotype than a pattern of homogeneous arrest, and the group with reduced spermatogenesis showed the mildest phenotype.