mTOR plays an important role in male fertility by integrating and mediating signals throughout the male reproductive system. It acts as a central regulator of spermatogenesis.
mTOR inhibitors like rapamycin have been shown to cause reversible infertility in men by reducing testosterone production and sperm counts.
mTORC1 and mTORC2 are expressed in germ cells and somatic cells of the testes, and each play distinct roles in regulating spermatogenesis.
mTORC1 is involved in Sertoli cell proliferation, metabolism, and redox balance, which impacts their ability to support germ cell development.
mTORC2 regulates the blood-testis barrier dynamics that allow preleptotene spermatocytes to enter the adluminal compartment for meiosis.
mTOR mediates the transcriptional and translational control of genes required for spermatogenesis at different stages.
Inhibition of mTORC1 blocks spermatogonial differentiation and entry into meiosis, suggesting it is required for germ cell development.
Dysregulation of mTOR signaling has been linked to defects in Sertoli cell polarity, germ cell apoptosis, and male infertility.
Targeting specific mTOR complexes may offer potential therapies for male fertility or male contraceptives.
Further research is needed to fully understand the distinct roles of mTORC1 and mTORC2 in the male reproductive system.
Any thoughts about this? Or a protocol that addresses this?
Hi! This is Shriya from the Healthspan Clinical Team! I had the chance to review the paper you shared and wanted to add some points. The paper, “Emerging Role for Mammalian Target of Rapamycin in Male Fertility” discusses the role of MTORC1 in spermatogenesis (sperm cell production). This article cites research from Hao Xu’s paper “mTOR/P70S6K promotes spermatogonia proliferation and spermatogenesis in Sprague Dawley rats” as the basis of its claims on rapamycin’s inhibition of mTOR and the ultimate decrease sperm production. (https://www.rbmojournal.com/article/S1472-6483(15)00551-9/fulltext)
I had the chance to review this research and one key takeaway is the dosing used in this study. This study used rats and injected rapamycin daily using a 2 mg per kilogram of body weight dosing schedule. If this dosage was used in a 160 pound adult (72 kg) they would receive 114 mg of rapamycin daily.
This is an incredible high dose of rapamycin in comparison to the Healthspan protocols which range from 3-8 mg per week. The key to our rapamycin protocol is our low-doses. These low-doses allow for temporary inhibition of the mTOR complexes for anti-aging purposes, while also leaving the opportunity for the mTOR complex to complete its vital functions in the body.
Hopefully this information was helpful in both understanding some current research on rapamycin/mTOR/fertility!
If you have further questions or concerns about your specific regiment we recommend reaching out to our Healthspan physicians so that we can provide you with the best protocol!