Abstract
Exposure of mouse spermatozoa and oocytes duringin vitro fertilization (IVF) to lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) activated macrophages (U937 cell line), but not unactivated macrophages cultureconditioned medium or control medium (RMPI+DMEM with 0.5% FBS) resulted in inhibition of IVF (87.2%), first cleavage (90.8%) and total blastocyst formation 97.5%). The direct coculture of the activated macrophages with 2-cell stage embryos resulted in arrested development (91.2%), an effect that was significantly diminished in the presence of monolayer of human endometrial stromal cells in the coculture (58.3%). In contrast, the majority of 2-cell embryos developed to blastocysts when exposed to unactivated macrophages, or macrophage-stromal cell cocultures (94.1%). The majority of 2-cell embryos cultured in control medium (DMEM/Ham’s F12 with 2% FBS) developed to morulae (96.2%), then underwent growth arrest and degeneration. Furthermore, culturing blastocyst stage embryos in the above groups resulted in a significant enhancement of trophoblast outgrowth, particularly in coculture with activated macrophages as compared to any other group (P<0.005). There was a significant increase in the levels of TGF-β, GM-CSF, IL-1α, IL-1β, TNF-α, PGE2, TXB2 and LTB4 released into the culture conditioned medium of activated macrophages compared to unactivated macrophages (P<0.001). These results suggest that the secretory products of activated macrophages, among them those determined in this study, in a stage-specific manner can directly effect sperm-egg interaction, early embryonic development and trophoblastic outgrowth. This data provides further support for the hypothesis that in endometriosis-associated infertility, continuous exposure of spermatozoa, oocytes and early embryos to activated macrophage-derived factors may play a vital role in their survival during transportation and fertilization as well as development during early embryonic stage.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bongso, A., Ng, S.C., Fong, C.Y. & Ratnam, S. (1991).Fertil. Steril.,56, 179–191.
Brannstrom, M. & Norman, R.J. (1993).Hum. Reprod.,8, 1762–1775.
Chaouat, G., Menu, E., Clark, D.A., Minkowsky, M., Dy, M. & Wegmann, T.G. (1990).J. Reprod. Fertil.,89, 447–458.
Chegini, N., Rossi, M.J. & Masterson, B.J. (1992).Endocrinology,130, 2373–2385.
Chegini, N., Zhao, Y. & McLean, F.W. (1994a).Biol. Reprod.,50, 1049–1058.
Chegini, N., Zhao, Y., Williams, R.S. & Flanders, K.C. (1994b).endocrinology,135, 439–449.
Chegini, N., Gold, L.I. & Williams, R.S. (1994c).Obstet. Gynecol.,83, 455–461.
Clark, D.A., Lea, R.G., Podor, T., Daya, S., Banwatt, D. & Harley, C. (1991).Ann. NY Acad. Sci.,626, 524–536.
Freeman, M.R., Bastias, M.C., Hill, G.A. & Osteen, K.G. (1993).Fertil. Steril.,59, 138–142.
Fukuda, A., Mori, T., Mori, E., Tatsumi K., Kanzaki, H. & Mori T. (1989).J. In. Vitro. Fertil. Embryo. Transf.,6, 59–64.
Guidice, L.C. (1994).Fertil. Steril.,61, 1–17.
Haimovici, F. & Anderson, D.J. (1993).Biol. Reprod.,49, 124–130.
Haimovici, F., Hill, J.A. & Anderson, D.J. (1991).Biol. Reprod.,44, 69–75.
Healy, D.L. (1991).Baillieres Clin. Obstet. Gynaecol.,5, 95–105.
Hill, J.A., Haimovici, F. & Anderson, D.J. (1987).J. Immunol.,139, 2250–2254.
Honda, R., Matsuura, K., Fukumatsu, Y., Kawano, T. & Okamura, H. (1994).Human Reprod.,9, 692–696.
Hunt, J.S. & Pollard, J.W. (1992).Current Topics Microbiol. Immunol.,181, 39–63.
Juneja, S.G. & Dodson, M.G. (1990).Can. J. Physiol. Pharmacol.,68, 1457–1460.
Juneja, S.C. & Williams, R.S. (1993).Life Sci.,53, 279–284.
Kabawat, S.E., Mostouri-Zadeh, M., Driscoli, S.G. & Bhan, A.K. (1985).Am. J. Pathol.,118, 76–84.
Kanzaki, H., Crainie, M., Lin, H., Yui, J., Guilbert, L.J., Mori, T. & Wegmann, T.G. (1991).Growth Factors,5, 69–74.
Kervancioglu, M.E., Djahanbakhch, O. & Aitken, R.J. (1994).Fertil. Steril.,61, 1103–1108.
Lea, R.G. & Clark, D.A. (1991).Baillieres Clin. Obstet. Gynaecol.,5, 25–59.
Lea, R.G. & Clark, D.A. (1993).Biol. Reprod.,48, 930–935.
Lyons, B.A. & Ashman, L.K. (1989).Human Monocytes. Zembala, M. & Asherson, G.L. (eds.). Academic Press Inc.: San Diego. pp. 59–69.
Mori, T., Takakura, K., Narimoto, K., Kariya, M., Imai, K., Fujiwara, H., Okamoto, N., Kariya, Y., Shiotani, M., Umaoka, Y., Kanzaki, H., Noda, Y. & Uchida, A. (1991).Ann. NY Acad. Sci. 626, 321–330.
Pampfer, S., Arceci, R.J. & Pollard, J.W. (1991).Bioessays,13, 535–540.
Pfeifer, T.L. & Chegini, N. (1994).Biol. Reprod. 50, 281–289.
Ramey, J.W. & Archer, D.F. (1993).Fertil. Steril.,60, 1–14.
Rappolee, D.A. & Werb, Z. (1992).Macrophage-derived growth factor,181, 87–140.
Robertson, S.A. & Seamark, R.F. (1992).Reprod. Fertil. Dev.,4, 435–448.
Schneider, E.G., Armant, D.R., Kupper, T.S. & Polan, M.L. (1989).Biol. Reprod.,40, 825–833.
Schomberg, D.W. (1989).Growth factors and the ovary. Hershfield, A.N. (eds) Plenum Press: New York. pp. 131–139.
Schultz, G.A. & Hevner, S. (1993).Oxf. Rev. Reprod. Biol.,15, 43–81.
Simmen, F.A. & Simmen, R.C.M. (1991).Biol. Reprod. 44, 1–5.
Simms, J.S., Chegini, N., Williams, R.S., Rossi, A.M. & Dunn, Jr, W.A. (1991).Obstet. Gynecol.,78, 850–857.
Sionov, R.V., Yagel, S., Har-Nir, R. & Gallily, R. (1993).Biol. Reprod.,49, 588–595.
Storeng, R. & Johne, B. (1987).Acta. Pathol. Microbiol. Immunol. Scand. B.,95, 135–139.
Sundstrom, C. & Nilsson, K. (1976).Int. J. Cancer.17, 565–577.
Tabibzadeh, S. (1991).Endocrine. Rev.,12, 272–290.
Tang, X.-M., Rossi, M.J., Masterson, B.J. & Chegini, N. (1994a).Biol. Reprod.,50, 1113–1125.
Tang, X.-M., Zhao, Y., Rossi, M.J., Abu-Rustum, R.S., Kasander, G. & Chegini, N. (1994b).Endocrinology,135, 450–459.
Watson, A.J., Watson P.H., Arcellana-Panlilio, M., Warnes, D., Walker, S.K., Schultz, G.A., Armestrong, D.T. & Seamark, R.F. (1994).Biol. Reprod.,50, 725–733.
Wiebel, E.R. (1979).Stereological methods, Vol. I. Academic Press: London.
Yeung, W.S.B., Ng, V.K.H., Lau, E.Y.L. & Ho, P.C. (1994).Hum. Reprod.,9, 656–660.
Zhao, Y., Chegini, N. & Flanders, K.C. (1994).J. Clin. Endocrinol. Metabol.,79, 1177–1184.
Zhao, Y. & Chegini, N. (1994).J. Clin. Endocrinol. Metab.,79, 662–665.
Author information
Authors and Affiliations
Additional information
S.C.J. and T.L.P. must be considered as equal contributors to this work
This work was supported in part by a Grant from Children’s Miracle Network to TLP.
Rights and permissions
About this article
Cite this article
Juneja, S.C., Pfeifer, T.L., Tang, X.M. et al. Modulation of mouse sperm-egg interaction, early embryonic development and trophoblastic outgrowth by activated and unactivated macrophages. Endocr 3, 69–79 (1995). https://doi.org/10.1007/BF02917451
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02917451