Undernutrition and laterality of the corpus luteum affects gene expression in oviduct and uterus of pregnant ewes

V. de Brun, J. A. Abecia, A. Fernandez-Foren, M. Carriquiry, F. Forcada, I. Vazquez, A. Meikle, C. Sosa


The effect of undernutrition on gene expression of progesterone and oestrogen receptors (PGR and ESR1), and insulin-like growth factors 1 and 2 (IGF1 and IGF2) in the uterus and oviducts of ewes on day 5 after oestrus was investigated. The effect of the side of the uterus/oviduct regarding the ovary bearing a corpus luteum (CL) (ipsi vs. contralateral) was also analyzed. Fourteen oestrous synchronized ewes were fed either 1.5 (C, n=7) or 0.5 (L, n=7) times their maintenance requirements from the onset of the hormonal treatment (day -14), till slaughter on day 5 post-oestrus. Oviducts and samples of uterus were collected and their gene expression studied by real time RT-PCR. Undernourished ewes had greater PGR expression in the oviduct than control ewes, but lower expression of IGF1 in uterus and of IGF2 in oviducts. The ipsilateral oviduct presented lower expression of PGR, ESR1 and IGF2 mRNA than the contralateral one, but this did not occur in the uterus. In conclusion, there is an effect of undernutrition on gene expression that is transcript and organ dependent (uterus/oviduct). This work reports for the first time that growth factors and sex steroid receptor expression on day 5 after oestrus vary depending on the side of the CL-bearing ovary and the region of the reproductive tract.


nutrition; reproductive tract; steroid receptors; growth factors

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Abecia JA, Rhind SM, Bramley T.A, McMillen SR, 1995. Steroid production and LH receptor concentration of ovarian follicles and corpora lutea and associated rates of ova wastage in ewes given high food intake before and after mating. J Anim Sci 60: 57-62. http://dx.doi.org/10.1017/S1357729800013515

Abecia JA, Forcad F, Zarazaga L, Lozano JM, 1996. The incidence of luteal activity as determined by peripheral plasma progesterone concentration, before the onset of breeding season in the Rasa Aragonesa breed of sheep. Br Vet J 15(3): 353-355. http://dx.doi.org/10.1016/S0007-1935(96)80108-4

Abecia JA, Lozano, JM, Forcada F, Zaragoza L, 1997. Effect of level of dietary energy and protein on embryo survival and progesterone production on day eight of pregnancy in Rasa Aragonesa ewes. Anim Reprod Sci 48: 209-218. http://dx.doi.org/10.1016/S0378-4320(97)00021-3

Abecia JA, Sosa C, Forcada F, Meikle A, 2006. The effect of undernutrition on the establishment of pregnancy in the ewe. Reprod Nutr Dev 46: 367–378. http://dx.doi.org/10.1051/rnd:2006018 PMid:16824446

AFRC, 1993. Energy and protein requirements of ruminants. An advisor manual prepared by the Agricultural and Food Research Council Technical Committee on responses to nutrients. CAB Intnal, Wallingford, UK.

Ashworth CJ, 1995. Maternal and conceptus factors affecting histotrophic nutrition and survival of embryos. Livest Prod Sci 44: 99-105. http://dx.doi.org/10.1016/0301-6226(95)00045-5

Bauersachs S, Blum H, Mallokm S, Wenigerkind H, Rief S, Prelle K, Wolf E, 2003. Regulation of ipsilateral and contralateral bovine oviduct epithelial cell function in the postovulation period: a transcriptomic approach. Biol Reprod 68: 1170-1177. http://dx.doi.org/10.1095/biolreprod.102.010660 PMid:12606461

Bonnin P, Huynh L, L’Haridon R, Chene N, Martal J, 1999. Transport of uterine PGF2α to the ovaries by systemic circulation and local lymphovenous-arterial diffusion during luteolysis in sheep. J Reprod Fertil 116: 119-210. http://dx.doi.org/10.1530/jrf.0.1160199

Chen Y, Green JA, Antoniou E, Early AD, Mathialagan N, Walker AM, 2006. Effect of interferon-tau administration on endometrium of nonpregnant ewes: a comparison with pregnant ewes. Endocrinology 147: 2127-2137. http://dx.doi.org/10.1210/en.2005-1310 PMid:16469802

Del Campo MR, Ginther OJ, 1973. Vascular anatomy of the uterus and ovaries and the unilateral luteoytic effect of the uterus: angio-architecture in sheep. Am J Vet Res 34: 1377-1385. PMid:4795932

Del Campo MR, Rowe RF, Ginther OJ, 1979. Relationship between side of embryo transfer and pregnancy rate in cattle. J Anim Sci 152: 290.

Einer-Jensen N, McCracken JA, 1981. The transfer of progesterone in the ovarian vascular pedicle of the sheep. Endocrinology 109(3): 685-690. http://dx.doi.org/10.1210/endo-109-3-685 PMid:7262016

Evans RW, Chen TJ, Hendry III WJ, Leavit WW, 1980. Progesterone regulation of estrogen receptor in the hamster uterus during the estrous cycle. Endocrinology 107: 383-390. http://dx.doi.org/10.1210/endo-107-2-383 PMid:7190093

Geisert RD, Short EC, Zavy MT, 1992. Maternal recognition of pregnancy. Anim Reprod Sci 28: 287-298. http://dx.doi.org/10.1016/0378-4320(92)90115-T

Kaye PL, Bell KL, Beebe LFS, Dunglison GF, Gardner HG, Harvey MB, 1992. Insulin and the insulin-like growth factors (IGFs) in preimplantation development. Reprod Fertil Dev 4: 373-386. http://dx.doi.org/10.1071/RD9920373 PMid:1461989

Kaye PL, 1997. Preimplantation growth factor physiology. Rev Reprod 2: 121-127. http://dx.doi.org/10.1530/ror.0.0020121 PMid:9414474

Lozano JM, Abecia JA, Forcada F, Zarazaga L, Alfaro B, 1998. Effect of undernutrition on the distribution of progesterone in the uterus of ewes during the luteal phase of the oestrus cycle. Theriogenology 49: 539-546. http://dx.doi.org/10.1016/S0093-691X(98)00005-3

Miller BG, Murphy L, Stone GM, 1977. Hormone receptor levels and hormone, RNA and protein metabolism in the genital tract during the oestrous cycle of the ewe. J Endocrinol 73: 91-98. http://dx.doi.org/10.1677/joe.0.0730091 PMid:558274

Moreno O, Cutaia L, Tribulo R, Caccia M, Videla Dorna I, Aba MA, Bo GA, 2003. Plasma progesterone, corpus luteum area and pregnancy rates in cows receiving embryos. Proc V Simposio Inter Reproducción Animal, Córdoba (Argentina).

Pantaleon M, Jericho H, Rabnott G, Kaye PL, 2003. The role of insulin-like growth factor II and its receptor in mouse preimplantation development. Reprod Fertil Dev 15: 37-45. http://dx.doi.org/10.1071/RD02031 PMid:12729502

Pflaffl MW, 2009. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9): e45. http://dx.doi.org/10.1093/nar/29.9.e45

Pflaffl MW, Georgieva TM, Georgiev IP, Ontsouka E, Hageleit M, Blum JW, 2002. Real time RT-PCR quantification of insulin-like growth factor (IGF)-I, IGF-I receptor, IGF-II, IGF-II receptor, insulin receptor, growth hormone receptor, IGF-binding proteins 1, 2 and 3 in the bovine species. Domest Anim Endocrinol 22: 91-102. http://dx.doi.org/10.1016/S0739-7240(01)00128-X

Rhind SM, Leslie ID, Gunn RG, Doney JM, 1985. Plasma FSH, LH, prolactin and progesterone profiles Cheviot ewes with different leves of intake before and after mating, and associated effects on reproductive performance. Anim Reprod Sci 8: 301-313. http://dx.doi.org/10.1016/0378-4320(85)90046-6

Russel AJF, Doney JM, Gunn RG, 1969. Subjective assessment of body fat in live sheep. J Agric Sci 72: 451-454. http://dx.doi.org/10.1017/S0021859600024874

Rutledge RG, Cote C, 2003. Mathematics of quantitative kinetic PCR and the application of standard curves. Nucleic Acids Res 31: e93. http://dx.doi.org/10.1093/nar/gng093 PMid:12907745 PMCid:PMC169985

Sahlin L, 1998. Insulin-like growth factor-I and thioredoxin in the uterus. Regulation by gonadal steroids and their relation to growth. Curr Top Steroid Res 1: 93-101.

Sosa C, Lozano J, Vi-oles C, Acu-a S, Abecia J, Forcada F, Forsberg M, Meikle A, 2004. Effect of plane of nutrition on endometrial sex steroid receptor expression in ewes. Anim Reprod Sci 84: 337-348. http://dx.doi.org/10.1016/j.anireprosci.2003.12.011 PMid:15302376

Sosa C, Abecia JA, Forcada F, Vi-oles C, Tasende C, Valares JA, Palacín I, Martin GB, Meikle A, 2006. Effect of undernutrition on uterine progesterone and oestrogen receptors and on endocrine profiles during the ovine oestrous cycle. Reprod Fertil Dev 18: 447-458. http://dx.doi.org/10.1071/RD05138 PMid:16737638

Sosa C, Abecia JA, Forcada F, Meikle A, 2008. Undernutrition reduces the oviductal mRNA expression of progesterone and oestrogen receptors in sheep. Vet J 175: 413-415. http://dx.doi.org/10.1016/j.tvjl.2007.01.018 PMid:17369061

Sosa C, Abecia JA, Carriquiri M, Forcada F, Martin GB, Palacín I, Meikle A, 2009. Early pregnancy alters the metabolic responses to restricted nutrition in sheep. Domest Anim Endocrinol 36: 13-23. http://dx.doi.org/10.1016/j.domaniend.2008.08.003 PMid:18838244

Spencer TE, Bazer FW, 1995. Temporal and spatial alterations in uterine estrogen receptor and progesterone receptor gene expression during the estrous cycle and early pregnancy in the ewe. Biol Reprod 53: 1527-1543. http://dx.doi.org/10.1095/biolreprod53.6.1527 PMid:8562711

Stevenson KR, Gilmour RS, Wathes DC, 1994. Localization of insulin-like growth factor-I and –II messenger ribonucleic acid and type 1 IGF receptors in the ovine uterus during the estrous cycle and early pregnancy. Endocrinology 134(4): 1655-1665. http://dx.doi.org/10.1210/en.134.4.1655 PMid:8137728

Stevenson KR, Wathes DC, 1996. Insulin-like growth factors and their binding proteins in the ovine oviduct during the oestrous cycle. J Reprod Fertil 108(1): 31-40. http://dx.doi.org/10.1530/jrf.0.1080031 PMid:8958825

Vasconcellos AC, Paredes MH, Barrietos EV, Olmazábal YS, Nú-ez DR, Navarrete JV, Molina BE, 2009. Analysis of the expression of estrogen receptors in the endometrium of ewes fed with normal and supplementary diet. Int J Morphol 27(4): 1093-1098.

Wathes DC, Reynolds TS, Robinson RS, Stevenson KR, 1998. Role of the insulin-like growth factor system in uterine function and placental development in ruminants. J Dairy Sci 81: 1778-1789. http://dx.doi.org/10.3168/jds.S0022-0302(98)75747-9

Weems CW, Weems YC, Lee CN, Vicent DL, 1989. Progesterone in uterine and arterial tissue and in jugular and uterine venous plasma of sheep. Biol Reprod 49: 1-6. http://dx.doi.org/10.1095/biolreprod41.1.1

Weems Y, Arreguin-Arevalo A, Nett T, Vann R, Ford S, Bridges P, Welsh T, Lewis A, Neuendorff D, Randel R, Weems Ch, 2011. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. I. Luteal weight, circulating progesterone, mRNA for luteal luteinizing hormone (LH) receptor, and occupied and unoccupied luteal receptors for LH. Prostaglandins Other Lipid Mediat 95: 35-44. http://dx.doi.org/10.1016/j.prostaglandins.2011.05.002

Wijayagunawardane MPB, Miyamoto A, Cerbito WA, Acosta TJ, Takagi M, Sato K, 1997. Local distribution of oviductal estradiol, progesterone, prostaglandins, oxytocin and endothelin-1 in the cyclic cow. Theriogenology 49: 607-618. http://dx.doi.org/10.1016/S0093-691X(98)00011-9

Wu SH, Weber WJ, Chester-Jones H, Hansen LB, Crooker BA, 2004. Effects of intake, selection for milk yield, and bST administration on hepatic expression of insulin receptors and components of the somatotropic axis in growing Holstein heifers. J Dairy Sci 87(S1): 364. Abstract W205.

DOI: 10.5424/sjar/2013114-3912