Chronic Asymptomatic Orchitis in Dogs Alters Sertoli Cell Number and Maturation Status

Overview

Journal Front Vet Sci

Specialty Veterinary Medicine

Date 2025 Feb 20

PMID 39974168

Authors

Pauline Rehder

Eva-Maria Packeiser

Hanna Korber

Sandra Goericke-Pesch

Affiliations

Soon will be listed here.

Abstract

Infertility due to non-obstructive azoospermia is a common diagnosis in infertile male dogs. Chronic asymptomatic orchitis (CAO) has been postulated as a significant cause of non-obstructive azoospermia in acquired male canine infertility. Despite severe microenvironmental changes, some resilient spermatogonial stem cells persist in CAO-affected testes. As Sertoli cells play an essential role in spermatogenesis and the testicular micromilieu, they represent a new target for CAO potential treatment and consequently deserve further investigation. To investigate Sertoli cell number and maturational status, different markers [Vimentin, anti-Müllerian hormone (AMH), and cytokeratin-18 (CK18)] were evaluated in healthy and CAO-affected testes at mRNA and protein levels. Sertoli cell number was reduced in CAO-affected dogs. Sertoli cells also partly returned to an immature status, as indicated by the expression of AMH and CK18 at mRNA and protein levels. The degree of spermatogenesis disruption matched with the degree of Sertoli cell alterations. The investigation of CAO in this study is limited by the number of samples and the lack of testicular volume measurements, but this does not diminish its importance in new findings. In conclusion, this study identifies alterations in Sertoli cell number and maturation status as a cause or consequence of CAO. The results indicate the need to restore Sertoli cell function as a potential therapeutic target for a successful restart of spermatogenesis.

References

Balogh O, Somoskoi B, Kollar E, Kowalewski M, Gram A, Reichler I . Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog. Theriogenology. 2021; 175:100-110. DOI: 10.1016/j.theriogenology.2021.08.017. View

Bar-Shira Maymon B, Paz G, Elliott D, Hammel I, Kleiman S, Yogev L . Maturation phenotype of Sertoli cells in testicular biopsies of azoospermic men. Hum Reprod. 2000; 15(7):1537-42. DOI: 10.1093/humrep/15.7.1537. View

Ball B, Conley A, Grundy S, Sabeur K, Liu I . Expression of anti-Müllerian hormone (AMH) in the equine testis. Theriogenology. 2008; 69(5):624-31. DOI: 10.1016/j.theriogenology.2007.11.009. View

Korber H, Goericke-Pesch S . Expression of PTGS2, PGFS and PTGFR during downregulation and restart of spermatogenesis following GnRH agonist treatment in the dog. Cell Tissue Res. 2018; 375(2):531-541. DOI: 10.1007/s00441-018-2915-x. View

Franke W, Grund C, Schmid E . Intermediate-sized filaments present in Sertoli cells are of the vimentin type. Eur J Cell Biol. 1979; 19(3):269-75. View

Goericke-Pesch S, Reifarth L, Behrens Mathiesen C, Schuler G, Umbach A, Korber H . Chronic Immune-Mediated Orchitis Is the Major Cause of Acquired Non-obstructive Azoospermia in Dogs. Front Vet Sci. 2022; 9:865967. PMC: 9010537. DOI: 10.3389/fvets.2022.865967. View

Rey R . Endocrine, paracrine and cellular regulation of postnatal anti-müllerian hormone secretion by sertoli cells. Trends Endocrinol Metab. 2008; 9(7):271-6. DOI: 10.1016/s1043-2760(98)00069-1. View

Hentrich A, Wolter M, Szardening-Kirchner C, Luers G, Bergmann M, Kliesch S . Reduced numbers of Sertoli, germ, and spermatogonial stem cells in impaired spermatogenesis. Mod Pathol. 2011; 24(10):1380-9. DOI: 10.1038/modpathol.2011.97. View

Davidson A, von Dehn B, Schlafer D . Adult-onset lymphoplasmacytic orchitis in a Labrador retriever stud dog. Top Companion Anim Med. 2015; 30(1):31-4. DOI: 10.1053/j.tcam.2015.03.003. View

10.

Paranko J, Kallajoki M, Pelliniemi L, Lehto V, Virtanen I . Transient coexpression of cytokeratin and vimentin in differentiating rat Sertoli cells. Dev Biol. 1986; 117(1):35-44. DOI: 10.1016/0012-1606(86)90345-3. View

11.

Patriarca C, Colecchia M, Clerici C . Enrico Sertoli and the supporting cells of the testis "". Pathologica. 2020; 111(4):375-381. PMC: 8145671. DOI: 10.32074/1591-951X-32-19. View

12.

Reifarth L, Korber H, Packeiser E, Goericke-Pesch S . Detection of spermatogonial stem cells in testicular tissue of dogs with chronic asymptomatic orchitis. Front Vet Sci. 2023; 10:1205064. PMC: 10311113. DOI: 10.3389/fvets.2023.1205064. View

13.

Martinez-Hernandez J, Seco-Rovira V, Beltran-Frutos E, Ferrer C, Serrano-Sanchez M, Pastor L . Proliferation, apoptosis, and number of Sertoli cells in the Syrian hamster during recrudescence after exposure to short photoperiod†‡. Biol Reprod. 2019; 102(3):588-597. DOI: 10.1093/biolre/ioz198. View

14.

Lackgren G, Ploen L . The morphology of the human undescended testis with special reference to the Sertoli cell and puberty. Int J Androl. 1984; 7(1):23-38. DOI: 10.1111/j.1365-2605.1984.tb00757.x. View

15.

Ahmed E, Barten-van Rijbroek A, Kal H, Sadri-Ardekani H, Mizrak S, van Pelt A . Proliferative activity in vitro and DNA repair indicate that adult mouse and human Sertoli cells are not terminally differentiated, quiescent cells. Biol Reprod. 2009; 80(6):1084-91. DOI: 10.1095/biolreprod.108.071662. View

16.

Cai G, Si M, Li X, Zou H, Gu J, Yuan Y . Zearalenone induces apoptosis of rat Sertoli cells through Fas-Fas ligand and mitochondrial pathway. Environ Toxicol. 2019; 34(4):424-433. DOI: 10.1002/tox.22696. View

17.

Zhang Z, Hu Z, Song X, Xiao L, Zou R, Han C . Disrupted expression of intermediate filaments in the testis of rhesus monkey after experimental cryptorchidism. Int J Androl. 2004; 27(4):234-9. DOI: 10.1111/j.1365-2605.2004.00477.x. View

18.

Tanwar P, Kaneko-Tarui T, Zhang L, Rani P, Taketo M, Teixeira J . Constitutive WNT/beta-catenin signaling in murine Sertoli cells disrupts their differentiation and ability to support spermatogenesis. Biol Reprod. 2009; 82(2):422-32. PMC: 2809230. DOI: 10.1095/biolreprod.109.079335. View

19.

Nistal M, Paniagua R, Abaurrea M, Santamaria L . Hyperplasia and the immature appearance of Sertoli cells in primary testicular disorders. Hum Pathol. 1982; 13(1):3-12. DOI: 10.1016/s0046-8177(82)80132-9. View

20.

Blanco-Rodriguez J, Martinez-Garcia C . Spontaneous germ cell death in the testis of the adult rat takes the form of apoptosis: re-evaluation of cell types that exhibit the ability to die during spermatogenesis. Cell Prolif. 1996; 29(1):13-31. DOI: 10.1111/j.1365-2184.1996.tb00091.x. View