TY - JOUR
T1 - Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment
AU - Chan, Jennifer C.
AU - Morgan, Christopher P.
AU - Adrian Leu, N.
AU - Shetty, Amol
AU - Cisse, Yasmine M.
AU - Nugent, Bridget M.
AU - Morrison, Kathleen E.
AU - Jašarević, Eldin
AU - Huang, Weiliang
AU - Kanyuch, Nickole
AU - Rodgers, Ali B.
AU - Bhanu, Natarajan V.
AU - Berger, Dara S.
AU - Garcia, Benjamin A.
AU - Ament, Seth
AU - Kane, Maureen
AU - Neill Epperson, C.
AU - Bale, Tracy L.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis. Here, we report reproductive tract EVs transmit information regarding stress in the paternal environment to sperm, potentially altering fetal development. Using intracytoplasmic sperm injection, we found that sperm incubated with EVs collected from stress-treated epididymal epithelial cells produced offspring with altered neurodevelopment and adult stress reactivity. Proteomic and transcriptomic assessment of these EVs showed dramatic changes in protein and miRNA content long after stress treatment had ended, supporting a lasting programmatic change in response to chronic stress. Thus, EVs as a normal process in sperm maturation, can also perform roles in intergenerational transmission of paternal environmental experience.
AB - Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis. Here, we report reproductive tract EVs transmit information regarding stress in the paternal environment to sperm, potentially altering fetal development. Using intracytoplasmic sperm injection, we found that sperm incubated with EVs collected from stress-treated epididymal epithelial cells produced offspring with altered neurodevelopment and adult stress reactivity. Proteomic and transcriptomic assessment of these EVs showed dramatic changes in protein and miRNA content long after stress treatment had ended, supporting a lasting programmatic change in response to chronic stress. Thus, EVs as a normal process in sperm maturation, can also perform roles in intergenerational transmission of paternal environmental experience.
UR - http://www.scopus.com/inward/record.url?scp=85082148006&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15305-w
DO - 10.1038/s41467-020-15305-w
M3 - Article
C2 - 32198406
AN - SCOPUS:85082148006
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1499
ER -