Abstract
The aim of this study was to examine the effect of activators of protein kinase A — 3-isobutyl-1-methyl-xanthine (IBMX) and dibutyryl cyclic adenosine monophosphate (dbcAMP) — and of oxytocin (OT) on rabbit female reproductive function. We used equine chorionic gonadotropin (eCG) to improve follicular development and rabbit estrous synchronization and human chorionic gonadotropin (hCG) to induce ovulation. In the experimental group, the females were stimulated using gonadotropins together with either IBMX, dbcAMP or OT. In the animals kept until parturition, the conception rate, parturition rate, and numbers of stillborn and weaned pups were recorded. In the animals euthanized 18–19 hours after insemination, the eggs were flushed from the oviducts and cultured up to the blastocyst cell stage. Numbers of corpora lutea, zygotes, morulas and blastocysts were determined. Both dbcAMP and OT, but not IBMX, decreased conception and parturition rate. Both IBMX and OT, but not dbcAMP, decreased pup mortality rate. All three tested substances increased the weaning rate. Both IBMX and dbcAMP, but not OT, increased the numbers of corpora lutea, zygotes, and embryos at morula and hatching blastocyst stages. These observations confirm the stimulatory role of the protein kinase A-dependent signaling pathway activated by IBMX and dbcAMP in rabbit reproduction. OT may decrease pups mortality.
References
Makarewich A.V., Sirotkin A.V., Presumptive mediators of growth hormone action on insulinlike growth factor I release by porcine ovarian granulosa cells, Biol Signals Recept, 2000, 9, 248–254
Conti M., Specificity of the cyclic adenosine 3′,5′-monophosphate signal in granulosa cell function, Biol Reprod, 2002, 67, 1653–1661
Mehlmann L.M., Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation, Reproduction, 2005, 130, 791–799
Sirotkin A.V., Control of reproductive processes by growth hormone: extra- and intracellular mechanisms, Vet J, 2005, 170, 307–317
Hunzicker-Dunn M., Maizels, E.T., FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A, Cell Signal, 2006, 18, 1351–1359
Sirotkin A.V., Makarewich A.V., Genieser H.G., Kotwica J., Hetényi L., Effect of four c GMP analogues with different mechanisms of action on hormone release by porcine ovarian granulosa cells in vitro, Exp Clin Endocrinol Diabetes, 2000, 108, 214–219
La Polt P.S., Leung K., Ishimaru R., Tafoya M.A., You-Hsin Ch.J., Roles of cyclic GMP in modulating ovarian functions, Reprod Biomed Online, 2003, 6, 15–23
Makarewich A.V., Sirotkin A.V., The involvement of the GH/IGF-I axis in the regulation of secretory activity by bovine oviduct epithelial cells, Anim Reprod Sci, 1997, 48, 197–207
Orihuela P.A., Parada-Bustamante A., Cortés P.P., Gattica C., Croxsatto H.B., Estrogen receptor, cyclic adenosine monophosphate, and protein kinase A are involved in the nongenomic pathway by which estradiol accelerates oviductal oocyte transport in cyclic rats, Biol Reprod, 2003, 68, 1225–1231
Sirotkin A.V., Makarewich A.V., Grosmann R., Protein Kinases and Ovarian Functions, J Cell Physiol, 2010, 226, 37–45
Park J.Y., Richard F., Chun S.Y., Park J.H., Law E., Horner K., et al., Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicle, Mol Endocrinol, 2003, 17, 1117–1130
Masciarelli S., Horner K., Liu C., Park S.H., Hinckley M., Hockman S., et al., Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility, J Clin Invest, 2004, 114, 196–205
Mckenna S.D., Pietropaulo M., Tos E.G., Clark A., Fischer D., Kagan D., et al., Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulatinghormone-primedrats, Endocrinology, 2005, 146, 208–214
Sirotkin A.V., Chrenek P., Čurlej J., Záhradníková M., Effect of 3-isobutyl-1-methyl-xanthine on rabbit superovulation and egg recovery, Slovak J Anim. Sci., 2008, 41, 57–59
Murphy B.D., Dobias M., Homologous and heterologous ligands downregulate follicle stimulating hormone receptor mRNA in porcine granulosa cells, Mol Reprod Dev, 1999, 53, 198–207
Nakamura M., Nakamura K., Igarashi S., Tano M., Miyamoto K., Ibuky Y., et al., Interaction between activin A cAMP in the induction of FSH receptor in cultured rat granulosa cells, J Endocrinol, 1995, 147, 103–110
Tano M., Minegishi T., Nakamura K., Karino S., Ibuky Y., Miyamoto K., Transcriptional and posttranscriptional regulation of FSH receptor in rat granulosa cells by cyclic AMP and activin, J Endocrinol, 1997, 173, 465–473
Peegel H., Towns R., Nair A., Menon K.M., A novel mechanism for the modulation of luteinizing hormone receptor mRNA expression in the rat ovary, Mol Cell Endocrinol, 2005, 233, 65–72
Hosoi Y., Yoshimura Y., Atlas S.J., Adachi T., Wallach E.E., Effect of dibutyril cyclic AMP on oocyte maturation and ovulation in the perfused rabbit ovary, J Reprod Fertil, 1989, 85, 405–411
Sirotkin A.V., Balazi A., Makarewich A.V., Chrenek P., Application of protein kinase stimulators for control and improvement of reproductive functions, Slovak J Anim. Sci., 2010, 43, 60–62
Wathes D.C., Denning-Kendall P.A., Control of synthesis and secretion of ovarian oxytocin in ruminants, J Reprod Fertil Suppl, 1992, 45, 39–52
Schaeffer H.J., Sirotkin A.V., The release of insulin-like growth factor-I by luteinized human granulosa cells in vitro: Regulation by growth hormone, oxytocin, steroids and cAMP-dependent intracellular mechanisms, Exp Clin Endocrinol Diabetes, 1995, 103, 361–366
Makarewich A.V., Sirotkin A.V., Franek J., Kwon H.B., Bulla J., The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions, Exp Clin Endocrinol Diabetes, 2004, 112, 108–114
Viggiano M., Franchi A.M., Zicari J.L., Rettori V., Gimeno M. A., Kozlowski G.P., et al., The involvement of oxytocin in ovulation and in the outputs of cyclooxygenase and 5-lipoxygenase products from isolated rat ovaries, Prostaglandins, 1989, 37, 367–378
Sirotkin A.V., Obstetrics and gynecology advances, Regulators of ovarian functions, Nova Science Publishers, Inc., 2011
Gimpl G., Fahrenholz F., The oxytocin receptor system: structure, function, and regulation, Physiol Rev, 2001, 81, 629–683
Sirotkin A.V., Makarewich A.V., Kwon H.B, Kotwica J., Bulla J., Hetényi L., Do GH, IGF-I and oxytocin interact by regulating the secretory activity of porcine ovarian cells? J Endocrinol, 2001, 171, 475–480
Berisha B., Schams D., Ovarian functions in ruminants, Domest Anim Endocrinol, 2005, 29, 305–317
Niswender G.D., Davis T.L, Griffith R.J, Bogan R.L., Monser K., Bott R.C., et al., Judge, jury and executioner: the auto-regulation of luteal function, Soc Reprod Fertil, 2007, 64, 191–206
Skarzynski D.J., Ferreira-Dias G., Okuda K., Regulation of luteal function and corpus luteum regression in cows: hormonal control, immune mechanisms and intracellular communication, Reprod Domest Anim, 2008, 43Suppl 2, 57–65
Sirotkin A.V., Chrenek P., Pivko J., Balazi A., Makarewich A.V., Phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine affects ovarian morphology and stimulates reproduction in rabbits, Eur J Inflamm, 2010, 8, 173–179
Chrenek P., Grossmann R., Sirotkin A.V., The cAMP analogue, dbcAMP affects release of steroid hormones by cultured rabbit ovarian cells and their response to FSH, IGF-I and ghrelin, Eur J Pharmacol, 2010, 640, 202–205
Sirotkin A.V., Chadio S., Chrenek P., Xylouri E., Fotopouloy H., Phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine stimulates reproduction in rabbit females, Theriogenology, 2010, 74, 1321–1326
Hillier S.G., Gonadotropic control of ovarian follicular growth and development, Mol Cell Endocrinol, 2001, 179, 39–46
Craig J., Orisaka M., Wang H., Orisaka S., Thompson W., Zhu C., et al., Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death, Front Biosci, 2007, 12, 28–39
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Balazi, A., Sirotkin, A.V. & Chrenek, P. Activators of protein kinase A and oxytocin affect rabbit reproduction. cent.eur.j.biol. 7, 973–979 (2012). https://doi.org/10.2478/s11535-012-0089-1
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DOI: https://doi.org/10.2478/s11535-012-0089-1