Akt1 protects against germ cell apoptosis in the postnatal mouse testis following lactational exposure to 6-N-propylthiouracil.
Exposure to 6-propyl-2-thio-uracil (PTU), a neonatal goitrogen, leads to increased testis size and sperm production in rodents. Akt1, a gene involved in cell survival and proliferation is also phosphorylated by thyroxine (T(4)). Therefore, we examined the requirement for Akt1 in germ cell survival following PTU-induced hypothyroidism. Experiments were performed using Akt1+/+, Akt1+/-, and Akt1-/- mice. PTU was administered (0.01% w/v) via the drinking water of dams from birth to PND21. At PND15, T(4) serum levels were similar in all control groups, and significantly lower in all exposed groups with a dramatic decrease in Akt1-/- mice. PTU-exposed Akt1-/- testes displayed smaller tubules, increased apoptosis, delayed lumen formation, and increased inhibin B and AMH mRNA. Relative adult testis weights were similar in all exposure groups; however, no increase in daily sperm production was observed in PTU-exposed Akt1-/- mice. In conclusion, Akt1 contributes to the effects of thyroid hormone on postnatal testis development.
Department of Pathology and Laboratory Medicine, GE505, Brown University, Providence, RI 02912, USA.
Jeena
J
Santos-Ahmed
Caitlin
C
Brown
Stuart Duncan
SD
Smith
Paula
P
Weston
Teresa
T
Rasoulpour
Mary E
ME
Gilbert
Mary L
ML
Hixon
D000818:Animals; D000831:Animals, Newborn; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D013956:Antithyroid Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007265:Inhibins / Q000378:metabolism; D007774:Lactation / Q000187:drug effects / Q000502:physiology; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011441:Propylthiouracil / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014284:Triiodothyronine / Q000097:blood
D013956:Antithyroid Agents; D012333:RNA, Messenger; C422364:inhibin B; D014284:Triiodothyronine; D007265:Inhibins; D011441:Propylthiouracil; D054304:Anti-Mullerian Hormone; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt