Members of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway are present and active in human sperm.

Abstract:

OBJECTIVE:To investigate whether components of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway are present and active in human sperm. DESIGN:Comparative study. SETTING:Reproductive biology department. PATIENT(S):Nine sperm donors. INTERVENTION(S):Sperm were exposed to interferon-alpha (IFN-alpha), IFN-gamma, interleukin-12 (IL-12), Ca2+ ionophore (A23187), or progesterone under capacitating conditions. MAIN OUTCOME MEASURE(S):Cell lysates prepared from sperm and Jurkat T-cell line were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the expression of JAKs (1-3 and TYK 2) and STATs (1-6) was examined by Western blot analysis. Effect of IFN-alpha, IFN-gamma, IL-12, A23187, or progesterone on sperm STAT 1 or STAT 4 phosphorylation was determined by phospho-STAT 1 antibody or antiphosphotyrosine (APT) Western blot analysis. Indirect immunofluorescence and confocal laser scanning microscopy was used to confirm the specific staining of anti-TYK 2, anti-STAT 1, and anti-STAT 4 antibodies. RESULT(S):By Western blot analysis, only antibodies to TYK 2 of the JAK family, and antibodies to STAT 1 and STAT 4 members of the STAT family specifically recognized protein bands corresponding to TYK 2, STAT 1, and STAT 4 described in other cell types. By confocal microscopy, antibodies to TYK 2 reacted with the sperm tail as well as the apical region of sperm head, whereas antibodies to STAT 1 and STAT 4 reacted with the apical region of the sperm head. Tyrosine phosphorylation of STAT 1 in capacitated sperm was enhanced by IFN-alpha and IFN-gamma, and that of STAT 4 was enhanced by IL-12. Both A23187 and progesterone markedly inhibited tyrosine phosphorylation of sperm STAT 4. CONCLUSION(S):Members of the JAK/STAT proteins, TYK 2, STAT 1, and STAT 4 are present and active in human sperm. The localization of STAT 1 and STAT 4 proteins to the apical region of the sperm head and their activation by IFN-alpha, IFN-gamma, or IL-12 implicate a role for sperm STAT proteins in fertilization. We hypothesize that sperm-derived phosphorylated STAT 1 and STAT 4 could contribute to the pool of transcription factors during sperm-oocyte fusion as well as transmit signal to the oocyte nucleus. Therefore, defects in sperm TYK 2 and STAT 1- or STAT 4-mediated signaling pathway may have relevance to male factor infertility.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

D'Cruz OJ,Vassilev AO,Uckun FM

doi

10.1016/s0015-0282(01)01896-9

keywords:

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

258-66

issue

2

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(01)01896-9

journal_volume

76

pub_type

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