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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2017

Open Access 01-12-2017 | Research

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows

Authors: Ken-Go Hayashi, Misa Hosoe, Keiichiro Kizaki, Shiori Fujii, Hiroko Kanahara, Toru Takahashi, Ryosuke Sakumoto

Published in: Reproductive Biology and Endocrinology | Issue 1/2017

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Abstract

Background

Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis.

Methods

The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium.

Results

Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins were localized in luminal and glandular epithelial cells and stroma of the endometrium.

Conclusion

The present study showed that endometrial gene expression profiles are different between RB and non-RB cows. The identified candidate endometrial genes and functions in each endometrial compartment may contribute to bovine reproductive performance.
Appendix
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Literature
1.
Perez-Marin CC, Calero GV, Moreno LM. Clinical Approach to the Repeat Breeder Cow Syndrome. In: Perez-Marin CC, editor. A Bird’s-Eye View of Veterinary Medicine. INTECH Open Access Publisher; 2012. doi:10.​5772/​31374.
2.
Tanabe TY, Hawk HW, Hasler JF. Comparative fertility of normal and repeat-breeding cows as embryo recipients. Theriogenology. 1985;23:687–96.CrossRefPubMed
3.
Dochi O, Takahashi K, Hirai T, Hayakawa H, Tanisawa M, Yamamoto Y, Koyama H. The use of embryo transfer to produce pregnancies in repeat-breeding dairy cattle. Theriogenology. 2008;69:124–8.CrossRefPubMed
4.
Gustafsson H, Larsson K. Embryonic mortality in heifers after artificial insemination and embryo transfer: differences between virgin and repeat breeder heifers. Res Vet Sci. 1985;39:271–4.PubMed
5.
Albihn A, Gustafsson H, Rodriguez-Martinez H, Larsson K. Development of day 7 bovine demi-embryos transferred into virgin and repeat-breeder heifers. Anim Reprod Sci. 1989;21:161–76.CrossRef
6.
Katagiri S, Moriyoshi M. Alteration of the endometrial EGF profile as a potential mechanism connecting the alterations in the ovarian steroid hormone profile to embryonic loss in repeat breeders and high-producing cows. J Reprod Dev. 2013;59:415–20.CrossRefPubMedPubMedCentral
7.
Ponsuksili S, Murani E, Schwerin M, Schellander K, Tesfaye D, Wimmers K. Gene expression and DNA-methylation of bovine pretransfer endometrium depending on its receptivity after in vitro-produced embryo transfer. PLoS One. 2012;7:e42402.CrossRefPubMedPubMedCentral
8.
Walker CG, Littlejohn MD, Mitchell MD, Roche JR, Meier S. Endometrial gene expression during early pregnancy differs between fertile and subfertile dairy cow strains. Physiol Genomics. 2012;44:47–58.CrossRefPubMed
9.
Minten MA, Bilby TR, Bruno RG, Allen CC, Madsen CA, Wang Z, Sawyer JE, Tibary A, Neibergs HL, Geary TW, et al. Effects of fertility on gene expression and function of the bovine endometrium. PLoS One. 2013;8:e69444.CrossRefPubMedPubMedCentral
10.
Killeen AP, Morris DG, Kenny DA, Mullen MP, Diskin MG, Waters SM. Global gene expression in endometrium of high and low fertility heifers during the mid-luteal phase of the estrous cycle. BMC Genomics. 2014;15:234.CrossRefPubMedPubMedCentral
11.
Bauersachs S, Ulbrich SE, Gross K, Schmidt SE, Meyer HH, Einspanier R, Wenigerkind H, Vermehren M, Blum H, Sinowatz F, Wolf E. Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes. J Mol Endocrinol. 2005;34:889–908.CrossRefPubMed
12.
Mitko K, Ulbrich SE, Wenigerkind H, Sinowatz F, Blum H, Wolf E, Bauersachs S. Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle. Reproduction. 2008;135:225–40.CrossRefPubMed
13.
Mansouri-Attia N, Aubert J, Reinaud P, Giraud-Delville C, Taghouti G, Galio L, Everts RE, Degrelle S, Richard C, Hue I, et al. Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation. Physiol Genomics. 2009;39:14–27.CrossRefPubMed
14.
Forde N, Beltman ME, Duffy GB, Duffy P, Mehta JP, O’Gaora P, Roche JF, Lonergan P, Crowe MA. Changes in the endometrial transcriptome during the bovine estrous cycle: effect of low circulating progesterone and consequences for conceptus elongation. Biol Reprod. 2011;84:266–78.CrossRefPubMed
15.
Forde N, Carter F, Spencer TE, Bazer FW, Sandra O, Mansouri-Attia N, Okumu LA, McGettigan PA, Mehta JP, McBride R, et al. Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant? Biol Reprod. 2011;85:144–56.CrossRefPubMed
16.
Bauersachs S, Ulbrich SE, Reichenbach HD, Reichenbach M, Buttner M, Meyer HH, Spencer TE, Minten M, Sax G, Winter G, Wolf E. Comparison of the effects of early pregnancy with human interferon, alpha 2 (IFNA2), on gene expression in bovine endometrium. Biol Reprod. 2012;86:46.CrossRefPubMed
17.
Forde N, Duffy GB, McGettigan PA, Browne JA, Mehta JP, Kelly AK, Mansouri-Attia N, Sandra O, Loftus BJ, Crowe MA, et al. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiol Genomics. 2012;44:799–810.CrossRefPubMed
18.
Spencer TE, Forde N, Dorniak P, Hansen TR, Romero JJ, Lonergan P. Conceptus-derived prostaglandins regulate gene expression in the endometrium prior to pregnancy recognition in ruminants. Reproduction. 2013;146:377–87.CrossRefPubMedPubMedCentral
19.
Shimizu T, Krebs S, Bauersachs S, Blum H, Wolf E, Miyamoto A. Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium. Physiol Genomics. 2010;42A:290–300.CrossRefPubMed
20.
Sakumoto R, Hayashi KG, Saito S, Kanahara H, Kizaki K, Iga K. Comparison of the global gene expression profiles in the bovine endometrium between summer and autumn. J Reprod Dev. 2015;61:297–303.CrossRefPubMedPubMedCentral
21.
King GJ, Atkinson BA, Robertson HA. Development of the bovine placentome during the second month of gestation. J Reprod Fertil. 1979;55:173–80.CrossRefPubMed
22.
King GJ, Atkinson BA, Robertson HA. Development of the bovine placentome from days 20 to 29 of gestation. J Reprod Fertil. 1980;59:95–100.CrossRefPubMed
23.
King GJ, Atkinson BA, Robertson HA. Development of the intercaruncular areas during early gestation and establishment of the bovine placenta. J Reprod Fertil. 1981;61:469–74.CrossRefPubMed
24.
Filant J, Spencer TE. Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization. Int J Dev Biol. 2014;58:107–16.CrossRefPubMedPubMedCentral
25.
Pope WF, Maurer RR, Stormshak F. Distribution of progesterone in the uterus, broad ligament, and uterine arteries of beef cows. Anat Rec. 1982;203:245–50.CrossRefPubMed
26.
Ealy AD, Yang QE. Control of interferon-tau expression during early pregnancy in ruminants. Am J Reprod Immunol. 2009;61:95–106.CrossRefPubMed
27.
Dunne LD, Diskin MG, Sreenan JM. Embryo and foetal loss in beef heifers between day 14 of gestation and full term. Anim Reprod Sci. 2000;58:39–44.CrossRefPubMed
28.
Berg DK, van Leeuwen J, Beaumont S, Berg M, Pfeffer PL. Embryo loss in cattle between Days 7 and 16 of pregnancy. Theriogenology. 2010;73:250–60.CrossRefPubMed
29.
Kizaki K, Shichijo-Kizaki A, Furusawa T, Takahashi T, Hosoe M, Hashizume K. Differential neutrophil gene expression in early bovine pregnancy. Reprod Biol Endocrinol. 2013;11:6.CrossRefPubMedPubMedCentral
30.
da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.CrossRef
31.
Ushizawa K, Takahashi T, Hosoe M, Ishiwata H, Kaneyama K, Kizaki K, Hashizume K. Global gene expression analysis and regulation of the principal genes expressed in bovine placenta in relation to the transcription factor AP-2 family. Reprod Biol Endocrinol. 2007;5:17.CrossRefPubMedPubMedCentral
32.
Walker CG, Meier S, Mitchell MD, Roche JR, Littlejohn M. Evaluation of real-time PCR endogenous control genes for analysis of gene expression in bovine endometrium. BMC Mol Biol. 2009;10:100.CrossRefPubMedPubMedCentral
33.
Ushizawa K, Takahashi T, Hosoe M, Kizaki K, Hashizume K. Characterization and expression analysis of SOLD1, a novel member of the retrotransposon-derived Ly-6 superfamily, in bovine placental villi. PLoS One. 2009;4:e5814.CrossRefPubMedPubMedCentral
34.
Hayes JD, McLellan LI. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 1999;31:273–300.CrossRefPubMed
35.
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88.CrossRefPubMed
36.
Ilic Z, Crawford D, Vakharia D, Egner PA, Sell S. Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1. Toxicol Appl Pharmacol. 2010;242:241–6.CrossRefPubMed
37.
Kensler KH, Slocum SL, Chartoumpekis DV, Dolan PM, Johnson NM, Ilic Z, Crawford DR, Sell S, Groopman JD, Kensler TW, Egner PA. Genetic or pharmacologic activation of Nrf2 signaling fails to protect against aflatoxin genotoxicity in hypersensitive GSTA3 knockout mice. Toxicol Sci. 2014;139:293–300.CrossRefPubMedPubMedCentral
38.
Baranova H, Canis M, Ivaschenko T, Albuisson E, Bothorishvilli R, Baranov V, Malet P, Bruhat MA. Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis. Mol Hum Reprod. 1999;5:636–41.CrossRefPubMed
39.
Jackson LW, Schisterman EF, Dey-Rao R, Browne R, Armstrong D. Oxidative stress and endometriosis. Hum Reprod. 2005;20:2014–20.CrossRefPubMed
40.
Yokoi R, Hayashi M, Tamura T, Kobayashi K, Kuroda J, Kusama H, Kagami H, Ono T. Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage. J Toxicol Sci. 2008;33:585–98.CrossRefPubMed
41.
Celi P, Merlo M, Da Dalt L, Stefani A, Barbato O, Gabai G. Relationship between late embryonic mortality and the increase in plasma advanced oxidised protein products (AOPP) in dairy cows. Reprod Fertil Dev. 2011;23:527–33.CrossRefPubMed
42.
Loset M, Mundal SB, Johnson MP, Fenstad MH, Freed KA, Lian IA, Eide IP, Bjorge L, Blangero J, Moses EK, Austgulen R. A transcriptional profile of the decidua in preeclampsia. Am J Obstet Gynecol. 2011;204:84. e81-27.CrossRefPubMedPubMedCentral
43.
Johansson AS, Mannervik B. Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem. 2001;276:33061–5.CrossRefPubMed
44.
Gray CA, Bazer FW, Spencer TE. Effects of neonatal progestin exposure on female reproductive tract structure and function in the adult ewe. Biol Reprod. 2001;64:797–804.CrossRefPubMed
45.
46.
Almeida Fo AP, Ayalon N, Bartoov B. Progesterone receptors in the endometrium of normal and repeat-breeder cows. Anim Reprod Sci. 1987;14:11–9.CrossRef
47.
Boshier DP. A histological and histochemical examination of implantation and early placentome formation in sheep. J Reprod Fertil. 1969;19:51–61.CrossRefPubMed
48.
Spencer TE, Johnson GA, Bazer FW, Burghardt RC. Fetal-maternal interactions during the establishment of pregnancy in ruminants. Soc Reprod Fertil Suppl. 2007;64:379–96.PubMed
49.
50.
Lin Z, Li S, Feng C, Yang S, Wang H, Ma D, Zhang J, Gou M, Bu D, Zhang T, et al. Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility. Nat Genet. 2016;48:1508–16.CrossRefPubMed
51.
Schweikl H, Hiller KA, Eckhardt A, Bolay C, Spagnuolo G, Stempfl T, Schmalz G. Differential gene expression involved in oxidative stress response caused by triethylene glycol dimethacrylate. Biomaterials. 2008;29:1377–87.CrossRefPubMed
52.
Sorsa T, Salo T, Koivunen E, Tyynela J, Konttinen YT, Bergmann U, Tuuttila A, Niemi E, Teronen O, Heikkila P, et al. Activation of type IV procollagenases by human tumor-associated trypsin-2. J Biol Chem. 1997;272:21067–74.CrossRefPubMed
53.
Moilanen M, Sorsa T, Stenman M, Nyberg P, Lindy O, Vesterinen J, Paju A, Konttinen YT, Stenman UH, Salo T. Tumor-associated trypsinogen-2 (trypsinogen-2) activates procollagenases (MMP-1, −8, −13) and stromelysin-1 (MMP-3) and degrades type I collagen. Biochemistry. 2003;42:5414–20.CrossRefPubMed
54.
Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD. Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature. 1986;324:476–8.CrossRefPubMed
55.
Aardal S, Helle KB, Elsayed S, Reed RK, Serck-Hanssen G. Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments. J Neuroendocrinol. 1993;5:405–12.CrossRefPubMed
56.
Mahata SK, O’Connor DT, Mahata M, Yoo SH, Taupenot L, Wu H, Gill BM, Parmer RJ. Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest. 1997;100:1623–33.CrossRefPubMedPubMedCentral
57.
Helle KB, Corti A. Chromogranin A: a paradoxical player in angiogenesis and vascular biology. Cell Mol Life Sci. 2015;72:339–48.CrossRefPubMed
58.
Michael DD, Alvarez IM, Ocon OM, Powell AM, Talbot NC, Johnson SE, Ealy AD. Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm. Endocrinology. 2006;147:3571–9.CrossRefPubMed
59.
Kizaki K, Ushizawa K, Takahashi T, Yamada O, Todoroki J, Sato T, Ito A, Hashizume K. Gelatinase (MMP-2 and −9) expression profiles during gestation in the bovine endometrium. Reprod Biol Endocrinol. 2008;6:66.CrossRefPubMedPubMedCentral
60.
Ulbrich SE, Meyer SU, Zitta K, Hiendleder S, Sinowatz F, Bauersachs S, Buttner M, Frohlich T, Arnold GJ, Reichenbach HD, et al. Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy. Mol Cell Endocrinol. 2011;332:48–57.CrossRefPubMed
61.
Mamo S, Mehta JP, Forde N, McGettigan P, Lonergan P. Conceptus-endometrium crosstalk during maternal recognition of pregnancy in cattle. Biol Reprod. 2012;87:6. 1–9.CrossRefPubMed
62.
Tsai SJ, Wu MH, Chen HM, Chuang PC, Wing LY. Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology. 2002;143:2715–21.CrossRef
63.
Ostrup E, Bauersachs S, Blum H, Wolf E, Hyttel P. Differential endometrial gene expression in pregnant and nonpregnant sows. Biol Reprod. 2010;83:277–85.CrossRefPubMed
64.
Klein C. Novel equine conceptus-endometrial interactions on day 16 of pregnancy based on RNA sequencing. Reprod Fertil Dev. 2016;28:1712–20.CrossRef
Metadata
Title
Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows
Authors
Ken-Go Hayashi
Misa Hosoe
Keiichiro Kizaki
Shiori Fujii
Hiroko Kanahara
Toru Takahashi
Ryosuke Sakumoto
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2017
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-017-0237-6

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