Abstract
Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation. These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. In this study, we found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. To further understand the role of Mct8 during spermatogenesis, we generated Slc16a2 (encodes MCT8) knockout rats using CRISPR/Cas9. Serum THs (T3 and T4) level were significantly altered in Slc16a2 knockout rats when compared to wild-type littermates during early to late postnatal development. Unlike Slc16a2 knockout mice, Slc16a2 knockout rats showed growth delay during early to late postnatal development. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.
Highlights
Thyroid hormone (TH) has long been believed to play a minor role in male reproduction
As Sertoli, Leydig and Germ cell proliferation were reported to occur until p15 during rodent testis development[5] and as Mct[8] is the most efficient and specific TH transporter[3], highly regulated expression of Mct[8] during early testis development indicates the importance of TH action for testicular cell proliferation
The gene expressions for other TH transporters such as Oatp1c1, Lat[1] and Lat[2] were found to sharply increase during adulthood which may suggest for their role during adulthood
Summary
Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. Thyroid hormones (THs) are well known to play a crucial role in the development of the central nervous system and in the regulation of cellular differentiation and m etabolism[1,2] Both prohormone, thyroxine (T4) and relatively minimal amount of genomically active tri-iodothyronine (T3) secreted from thyroid gland can be actively transported into the cells via specific transporters expressed at the plasma membrane[1]. Human loss-of-function mutation of MCT8, Allan-Herndon-Dudley syndrome (AHDS) shows cryptorchidism
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