Search

Cryptorchidism causes spermatogenic failure and reduced serum androgen levels, as well as testicular oedema and fibrosis, which are hallmarks of inflammation. However, the role of inflammation and the effects of cryptorchidism on Sertoli cell and Leydig cell function at the molecular level remain ill-defined. Bilateral cryptorchidism was surgically induced in adult rats for 7 and 14 weeks. Testis weights decreased to 40% of normal within 7 weeks, due to loss of all developing spermatogenic cells except spermatogonia, but did not decrease further at 14 weeks. Serum FSH and LH were increased at both time points, consistent with a loss of feedback by inhibin and testosterone. This damage was accompanied by progressive accumulation of interstitial fluid and peritubular fibrosis, and a progressive decline of several critical Sertoli cell genes (Sox9, Inha (inhbin α-subunit), Cldn11 (claudin 11), Gja1 (connexin 43), and Il1a (interleukin-1α)) and the Leydig cell steroidogenic enzymes, Cyp11a1, Hsd3b1, and Hs17b3. Activin B and the activin-binding protein, follistatin, also declined, but the intratesticular concentration of activin A, which is a regulator of inflammatory responses, was largely unaffected at either time point. Expression of genes involved in inflammation (Tnf, Il10, Il1b, Mcp1) and fibrosis (Acta2, Col1a1) were considerably elevated at both time points. These data indicate that induction of experimental cryptorchidism, which causes complete failure of spermatogenesis in the adult rat, also induces chronic testicular inflammation, manifesting in oedema and fibrosis, and a progressive decline of Sertoli and Leydig cell gene expression and function.

The testis is a temperature-sensitive organ that needs to be maintained 2–7 °C below core body temperature to ensure the production of normal sperm. Failure to maintain testicular temperature in mammals impairs spermatogenesis and leads to low sperm counts, poor sperm motility and abnormal sperm morphology in the ejaculate. This review discusses the recent knowledge on the response of testicular somatic cells to heat stress and, specifically, regarding the relevant contributions of heat, germ cell depletion and inflammatory reactions on the functions of Sertoli and Leydig cells. It also outlines mechanisms of testicular thermoregulation, as well as the thermogenic factors that impact testicular function.

Heat reversibly disrupts spermatogenesis, but the effects on Sertoli cell (SC) function and inhibin/activin-related proteins are less well-defined. Adult rat testis weights decreased by 40% within 2 weeks after heat-treatment (43 °C, 15 min), due to loss of pachytene spermatocytes and round spermatids. Coincident effects were reduced SC nuclear volume at one week and >50% reduction in expression of several critical SC genes (Inha, Cld11, Gja1, Tjp1, Cldn3) by 2 weeks. Leydig cell steroidogenic enzymes, Cyp11a1, Hsd3b1, were also reduced. Activin gene expression was unaffected at this time, but expression of the activin-binding protein, follistatin (Fst), increased >2-fold. At 4–8 weeks, coincident with the recovery of spermatocytes and early spermatids, but progressive loss of elongated spermatids, most SC genes had recovered; however, testicular activin A was reduced and activin B increased. At 8 weeks, serum inhibin was decreased and, consequently, serum FSH increased. Crucially, germ cell damage was not associated with a significant inflammatory response. At 14 weeks, most testicular parameters had returned to normal, but testis weights remained slightly reduced. These data indicate that, following acute heat-treatment, expression of several key Sertoli and Leydig cell genes declined in parallel with the initial loss of meiotic germ cells, whereas activins were responsive to the subsequent loss of mature spermatids, leading to an increase in testicular activin B production relative to activin A.