Periconceptional growth hormone treatment alters early uterine environment

Jill M. Koch, Caleb O. Lemley, Ronald R. Magness, Matthew E. Wilson

Department of Medicine, Section of Cardiovascular Medicine, University of Wisconsin-Madison, Madison, USA.
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Natural Resources and Design, West Virginia University Morgantown, Morgantown, USA.
Perinatal Research Labs, Departments of Obstetrics and Gynecology and Department of Animal Science, University of Wisconsin, Madison, USA.

DOI: 10.4236/ojas.2013.32018                

Abstract

We have shown that an injection of sustained release growth hormone (GH), given just prior to breeding, results in lambs that are 25% heavier at birth, with an altered body composition as evidenced by an increased abdominal girth, but no difference in crown rump length. The mechanisms by which these differences occur from a single periconceptional injection are not yet known. Therefore, the objective of this experiment was to determine the effect of an injection of GH given prior to breeding on the composition of the uterine luminal environment and the embryo at the time of blastocyst. Ewes were synchronized with two injections of prostaglandin F₂α given eight days apart. On the day of the second injection, ewes were randomly assigned to be given an injection of sustained release GH or remain as controls and penned with a ram. On day 6.5 following breeding embryos were collected. Prior to surgery a jugular blood sample was taken to determine plasma progesterone and urea concentration. The uterine content of urea, prostaglandin F₂α, prostaglandin E₂, transforming growth factor β-1 (TGF β), and nitric oxide metabolites were measured. Collected embryos were differentially stained to calculate a trophectoderm to inner cell mass ratio. The concentration of progesterone in maternal plasma was greater in the treated group compare to controls, but blood urea nitrogen was not different between groups. The uterine content of urea in the GH group was lower than that of the control group. There was a trend for TGF β to be increased in the GH treated group compared to control (P = 0.07). There was no difference (P > 0.05) in the total uterine content prostaglandin F₂α, prostaglandin E₂ or nitric oxide metabolites. The trophectoderm to inner cell mass ratio was not different between treatment groups. Thus, we suggest that the observed difference in fetal development following periconceptional growth hormone administration just prior to breeding may be the result of an alteration in the uterine luminal environment, which may alter the cellular program of the conceptus and later development beyond the embryonic stage.

Keywords

Growth Hormone; Uterine Environment; Embryo

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Godfery, K.M. and Barker, D.J. (2000) Fetal nutrition and adult disease. American Journal of Clinical Nutrition, 71, 1344S-1352S.
[2]	Moore, N.W. and Shelton, J.N. (1964) Egg transfer in sheep: Effect of degree of synchronization between donor and recipient, age of egg, and site of transfer on the survival of transferred eggs. Journal of Reproduction and Fertility, 7, 145-152. doi:10.1530/jrf.0.0070145
[3]	Rowson, L.E.A. and Moor, R.M. (1966) Embryo transfer in the sheep: The significance of synchronizing oestrus in the donor and recipient animal. Journal of Reproduction and Fertility, 11, 207-212. doi:10.1530/jrf.0.0110207
[4]	Kleemann, D.O., Walker, S.K. and Seamark, R.F. (2004) Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy. Journal of Reproduction and Fertility, 102, 411-417. doi:10.1530/jrf.0.1020411
[5]	Young, L.E., Butterwith, S.C. and Wilmut, I. (1996) Increased ovine fetal weight following transient asynchronous embryo transfer is not associated with increased placental weight at day 21 of gestation. Theriogenology, 45, 231. doi:10.1016/0093-691X(96)84704-2
[6]	Costine, B.A., Inskeep, E.K. and Wilson, M.E. (2005) Growth hormone at breeding modifies concetpus development and postnatal growth in sheep. Journal of Animal Science, 83, 810-815.
[7]	Koch, J.M., Wilmoth, T.A. and Wilson, M.E. (2010) Periconceptional growth hormone treatment alters fetal growth and development in lambs. Journal of Animal Science, 88, 1619-1625. doi:10.2527/jas.2009-2392
[8]	Rivera, R.M., Youngs, C.R. and Ford, S.P. (1996) A comparison of the number of inner cell mass and trophectoderm cells of preimplantation Meishan and Yorkshire pig embryos at similar developmental states. Journal of Reproduction and Fertility, 106, 111-116. doi:10.1530/jrf.0.1060111
[9]	Sheffel, C.E., Pratt, B.R. Ferrell, W.L. and Inskeep, E.K. (1982) Induced corpora lutea in the postpartum beef cow. II. Effects of treatment with progestogen and gonadotropins. Journal of Animal Science, 54, 830-836.
[10]	Holaskova, I. (2007) Distribution of transforming growth factor β-1, TGF receptor II and decorin in the sheep uterus shortly after breeding II. Effect of TGFβ-1 on gene expression in the sheep uterus at the time of embryo attachment III. Concentration of TGFβ-1, 2, and 3 in beef bull and ram seminal plasma, Dissertation, West Virginia University, Morgantown.
[11]	Maxfield, E.K., Sinclair, K.D., Dunne, L.D., Broadbent, P.J., Robison, J.J., Steward, E., Kyle, D.G. and Maltin, C.A. (1998) Temporary exposure of ovine embryos to an advanced uterine environment does not affect fetal weight but alters fetal muscle development. Biology of Reproduction, 59, 321-325. doi:10.1095/biolreprod59.2.321
[12]	Ashworth, C.J. and Bazer, F.W. (1989) Changes in ovine conceptus and endometrial function following asynchronous embryo transfer or administration of progesterone. Biology of Reproduction, 40, 425-433. doi:10.1095/biolreprod40.2.425
[13]	Spencer, T.E. and Bazer, F.W. (2004) Uterine and placental factors regulating conceptus growth in domestic animals. Journal of Animal Science, 82, E4-E13.
[14]	Aguilar, J. and Reyley. M (2005) The uterine tubal fluid: secretion, composition and biological effects. Animal Reproduction, 2, 91-105.
[15]	Igwebuike, U.M. (2006) Trophoblast cells of ruminant placentas—A minireview. Animal Reproduction Science, 93, 185-198. Kleemann, D.O., Walker, S.K. and Seamark, R.F. Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy. Journal of Reproduction and Fertility, 102, 411-417.
[16]	Watson, A.J., Watson, P.H., Arcellanal-Panlilio, M., Warnes, D., Walker, S.K., Schultz, G.A., Armstrong, D.T. and Seamark, R.F. (1994) A growth phenotype map for ovine preimplantation and development. Biology of Reproduction, 50, 725-733. doi:10.1095/biolreprod50.4.725
[17]	Bauer, M.K., Harding, J.E., Bassett, N.S., Breier, B.H., Oliver, M.H., Gallaher, B.H., Evans, P.C., Woodall, S.M. and Gluckman, P.D. (1998) Fetal growth and placental function. Molecular and Cellular Endocrinology, 140, 115-120. doi:10.1016/S0303-7207(98)00039-2