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Review Question - QID 210081

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QID 210081 (Type "210081" in App Search)
A 31-year-old man with no medical history presents to his provider for infertility. He states that he and his partner have had unprotected intercourse for 1 year and have been unable to conceive. Upon further workup, he is determined to have antisperm antibodies (ASA), but he does not have any other signs or labs suggesting systemic autoimmune disease. A breakdown of which of the following may have played a role in the pathogenesis of his infertility?

Connexons

12%

14/116

Desmoplakins

2%

2/116

E-cadherins

22%

26/116

Integrins

15%

17/116

Occludins

41%

47/116

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The downregulation of occludins, which comprise the tight junctions of Sertoli cells, can lead to autoimmune attack through the blood-testis barrier and result in infertility.

Sertoli cells are non-germ cells in the seminiferous tubules that are connected to each other by tight junctions. These tight junctions form the blood-testis barrier, which isolate the gametes to prevent autoimmune reactions. Tight junctions, or zonulae occludentes (singular, zonula occludens), are composed of claudin and occludin proteins. During injury, the increase in inflammatory cytokines is believed to downregulate the expression of occludin proteins in Sertoli cells, which leads to the breakdown of tight junctions between cells. This then allows for communication through the blood-testis barrier.

Incorrect Answers:
Answer 1: Connexons are channel proteins that allow for communication between cells, but these are found at gap junctions, not tight junctions.

Answer 2: Desmoplakins are proteins found in desmosomes (macula adherens) in cardiac muscle and epidermal cells.

Answer 3: E-cadherins are found in the adherens junction (zonula adherens), which connects actin cytoskeletons between adjacent cells.

Answer 4: Integrins are proteins found in the basolateral surface of the cell that connect the cell membrane to the basement membrane or extracellular matrix.

Bullet Summary:
Tight junctions between Sertoli cells help comprise the blood-testis barrier, which prevent autoimmune attack against the testis.

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