title: Neurotensin enhances sperm capacitation and acrosome reaction in mice.
abstract: Neurotensin (NT) has multiple functions, ranging from acting as a neurotransmitter to regulating intestinal movement. However, its function in reproductive physiology is unknown. Here, we confirmed the expression and localization of NT receptors (NTR1) in mouse epididymal spermatozoa and investigated the effect of NT on sperm function. Sperm protein tyrosine phosphorylation, one of the indices of sperm capacitation, was facilitated dose-dependently by NT administration. In addition, the acrosome reaction was promoted in capacitated spermatozoa, and addition of a selective antagonist of NTR1 and NTR2 blocked the induction. Furthermore, intracellular calcium mobilization by NT addition was observed. This showed that NT was an accelerator of sperm function via its functional receptors. The presence of NT was confirmed by immunohistochemistry and its localization was observed in epithelia of the uterus and oviduct isthmus and ampulla, which correspond to the fertilization route of spermatozoa. The NT mRNA level in ovulated cumulus cell was remarkably increased by treatment with human chorionic gonadotropin (hCG). Using an in vitro maturation model, we analyzed the effects of FSH, epidermal growth factor (EGF), estradiol, and progesterone in NT production in cumulus cells. We found that FSH and EGF upregulated NT release and mRNA expression. Both FSH- and EGF-induced upregulation were inhibited by U0126, an MAPK kinase inhibitor, indicating that FSH and EGF regulate NT expression via a MAPK-dependent pathway. This evidence suggests that NT can act as a promoter of sperm capacitation and the acrosome reaction in the female reproductive tract.
authors.affiliation: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan hiradate@bios.tohoku.ac.jp.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hiradate
authors.affiliation: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shirakata
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Laboratory of Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Aina
authors.initials: A
authors.lastname: Gotoh
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Roh
authors.affiliation: Laboratory of Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Laboratory of Animal Physiology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Katoh
authors.affiliation: Misaki Marine Biological Station, Graduate School of Science, University of Tokyo, Kanagawa, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: National Livestock Breeding, Fukushima, Japan.
authors.forename: Eimei
authors.initials: E
authors.lastname: Sato
authors.affiliation: Laboratory of Animal Reproduction, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
mesh_terms: D020101:Acrosome Reaction / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005187:Fallopian Tubes / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism*; D013075:Sperm Capacitation / Q000187:drug effects* / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology; D014599:Uterus / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D002118:Calcium
keywords: acrosome reaction; capacitation; cumulus cells; fertilization; oviduct; ovulation; reproduction; sperm; uterus