Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-23T07:13:43.793Z Has data issue: false hasContentIssue false
  • English
  • Français

Central genomic regulation of the expression of oestrous behaviour in dairy cows: a review

Published online by Cambridge University Press:  06 March 2014

H. Woelders ,
T. van der Lende ,
A. Kommadath ,
M. F. W. te Pas ,
M. A. Smits  and
L. M. T. E. Kaal
H. Woelders
Affiliation:
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, P.O. Box 65, 8200 AB Lelystad, The Netherlands
T. van der Lende
Affiliation:
ProPhys Animal Science Consultancy, Klaproosdreef 21, 5288 JP Swifterbant, The Netherlands
A. Kommadath
Affiliation:
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, P.O. Box 65, 8200 AB Lelystad, The Netherlands
M. F. W. te Pas
Affiliation:
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, P.O. Box 65, 8200 AB Lelystad, The Netherlands
M. A. Smits*
Affiliation:
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, P.O. Box 65, 8200 AB Lelystad, The Netherlands
L. M. T. E. Kaal
Affiliation:
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, P.O. Box 65, 8200 AB Lelystad, The Netherlands
*
†E-mail: mari.smits@wur.nl
Get access

Abstract

The expression of oestrous behaviour in Holstein Friesian dairy cows has progressively decreased over the past 50 years. Reduced oestrus expression is one of the factors contributing to the current suboptimal reproductive efficiency in dairy farming. Variation between and within cows in the expression of oestrous behaviour is associated with variation in peripheral blood oestradiol concentrations during oestrus. In addition, there is evidence for a priming role of progesterone for the full display of oestrous behaviour. A higher rate of metabolic clearance of ovarian steroids could be one of the factors leading to lower peripheral blood concentrations of oestradiol and progesterone in high-producing dairy cows. Oestradiol acts on the brain by genomic, non-genomic and growth factor-dependent mechanisms. A firm base of understanding of the ovarian steroid-driven central genomic regulation of female sexual behaviour has been obtained from studies on rodents. These studies have resulted in the definition of five modules of oestradiol-activated genes in the brain, referred to as the GAPPS modules. In a recent series of studies, gene expression in the anterior pituitary and four brain areas (amygdala, hippocampus, dorsal hypothalamus and ventral hypothalamus) in oestrous and luteal phase cows, respectively, has been measured, and the relation with oestrous behaviour of these cows was analysed. These studies identified a number of genes of which the expression was associated with the intensity of oestrous behaviour. These genes could be grouped according to the GAPPS modules, suggesting close similarity of the regulation of oestrous behaviour in cows and female sexual behaviour in rodents. A better understanding of the central genomic regulation of the expression of oestrous behaviour in dairy cows may in due time contribute to improved (genomic) selection strategies for appropriate oestrus expression in high-producing dairy cows.

Keywords

sexual behaviourdairy cowoestrusgene expressionbrain
Type
Full Paper
Information
animal , Volume 8 , Issue 5 , May 2014 , pp. 754 - 764
Copyright
© The Animal Consortium 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

a

These authors contributed equally to this paper.

References

Allrich, RD 1994. Endocrine and neural control of estrus in dairy cows. Journal of Dairy Science 77, 2738–2744.Google Scholar
Amateau, SK and McCarthy, MM 2002. A novel mechanism of dendritic spine plasticity involving estradiol induction of prostaglandin-E2 . Journal of Neuroscience 22, 8586–8596.CrossRefGoogle ScholarPubMed
Billups, D, Billups, B, Challiss, RAJ and Nahorski, SR 2006. Modulation of Gq-protein-coupled inositol trisphosphate and Ca2+ signaling by the membrane potential. Journal of Neuroscience 26, 9983–9995.Google Scholar
Blaustein, JD 2008. Neuroendocrine regulation of feminine sexual behavior: lessons from rodent models and thoughts about humans. Annual Review of Psychology 59, 93–118.Google Scholar
Caldwell, HK and Albers, HE 2002. The effects of serotonin agonists on the hypothalamic regulation of sexual receptivity in Syrian hamsters. Hormones and Behavior 42, 78–84.Google Scholar
Cardona-Gómez, GP, Mendez, P, DonCarlos, LL, Azcoitia, I and Garcia-Segura, LM 2003. Interactions of estrogen and insulin-like growth factor-I in the brain: molecular mechanisms and functional implications. Journal of Steroid Biochemistry and Molecular Biology 83, 211–217.Google Scholar
Chagas, LM, Bass, JJ, Blache, D, Burke, CR, Kay, JK, Lindsay, DR, Lucy, MC, Martin, GB, Meier, S, Rhodes, FM, Roche, JR, Thatcher, WW and Webb, R 2007. Invited review: new perspectives on the roles of nutrition and metabolic priorities in the subfertility of high-producing dairy cows. Journal of Dairy Science 90, 4022–4032.Google Scholar
Clasadonte, J, Poulain, P, Hanchate, NK, Corfas, G, Ojeda, SR and Prevot, V 2011. Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation. Proceedings of the National Academy of Sciences of the United States of America 108, 16104–16109.CrossRefGoogle ScholarPubMed
Conaway, CH 1971. Ecological adaptation and mammalian reproduction. Biology of Reproduction 4, 239–247.CrossRefGoogle ScholarPubMed
Curley, JP and Keverne, EB 2005. Genes, brains and mammalian social bonds. Trends in Ecology and Evolution 20, 561–567.Google Scholar
Davidge, ST, Wiebold, JL, Senger, PL and Hillers, JK 1987. Influence of varying levels of blood progesterone upon estrous behavior in cattle. Journal of Animal Science 64, 126–132.Google Scholar
Delville, Y and Blaustein, JD 1991. A site for estradiol priming of progesterone-facilitated sexual receptivity in the ventrolateral hypothalamus of female guinea pigs. Brain Research 559, 191–199.Google Scholar
Dhali, A, Mishra, DP, Karunakaran, M, Mech, A and Rajkhowa, C 2006. Influence of plasma estradiol 17-β and progesterone levels on estrous behaviour in Mithun (Bos frontalis). Applied Animal Behaviour Science 98, 1–10.Google Scholar
Dijkhuizen, TJ and Van Eerdenburg, FJCM 1997. Behavioural signs of oestrus during pregnancy in lactating dairy cows. Veterinary Quarterly 119, 194–196.Google Scholar
Diskin, MG and Sreenan, JM 2000. Expression and detection of oestrus in cattle. Reproduction Nutrition Development 40, 481–491.Google Scholar
Dobson, H, Walker, SL, Morris, MJ, Routly, JE and Smith, RF 2008. Why is it getting more difficult to successfully artificially inseminate dairy cows? Animal 2, 1104–1111.CrossRefGoogle ScholarPubMed
Donaldson, ZR and Young, LJ 2008. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322, 900–904.Google Scholar
Dransfield, MBG, Nebel, RL, Pearson, RE and Warnick, LD 1998. Timing of insemination for dairy cows identified in estrus by a radiotelemetric estrus detection system. Journal of Dairy Science 81, 1874–1882.Google Scholar
Erb, RE, Chew, BP and Keller, HF 1977. Relative concentrations of estrogen and progesterone in milk and blood, and excretion of estrogen in urine. Journal of Animal Science 46, 617–626.Google Scholar
Esslemont, RJ, Glencross, RG, Bryant, MJ and Pope, GS 1980. A quantitative study of pre-ovulatory behaviour in cattle (British Friesian heifers). Applied Animal Ethology 6, 1–17.Google Scholar
Fabre-Nys, C 1998. Steroid control of monoamines in relation to sexual behaviour. Reviews of Reproduction 3, 31–41.Google Scholar
Fabre-Nys, C and Gelez, H 2007. Sexual behavior in ewes and other domestic ruminants. Hormones and Behavior 52, 18–25.Google Scholar
Fabre-Nys, C, Ohkura, S and Kendrick, KM 1997. Male faces and odours evoke differential patterns of neurochemical release in the mediobasal hypothalamus of the ewe during oestrus: an insight into sexual motivation? European Journal of Neuroscience 9, 1666–1677.Google Scholar
Fabre-Nys, C, Chesneau, D, De La Riva, C, Hinton, MR, Locatelli, A, Ohkura, S and Kendrick, KM 2003. Biphasic role of dopamine on female sexual behaviour via D2 receptors in the mediobasal hypothalamus. Neuropharmacology 44, 354–366.Google Scholar
Firk, R, Stamer, E, Junge, W and Krieter, J 2002. Automation of oestrus detection in dairy cows: a review. Livestock Production Science 75, 219–232.Google Scholar
Garcia, E, Hultgren, J, Fällman, P, Geust, J, Algers, B, Stilwell, G, Gunnarsson, S and Rodriguez-Martinez, H 2011. Oestrous intensity is positively associated with reproductive outcome in high-producing dairy cows. Livestock Science 139, 191–195.Google Scholar
Garnsworthy, PC, Sinclair, KD and Webb, R 2008. Integration of physiological mechanisms that influence fertility in dairy cows. Animal 2, 1144–1152.Google Scholar
Gilmore, HS, Young, FJ, Patterson, DC, Wylie, ARG, Law, RA, Kilpatrick, DJ, Elliott, CT and Mayne, CS 2011. An evaluation of the effect of altering nutrition and nutritional strategies in early lactation on reproductive performance and estrous behavior of high-yielding Holstein-Friesian dairy cows. Journal of Dairy Science 94, 3510–3526.Google Scholar
Gispen, WH, Nielander, HB, De Graan, PNE, Oestreicher, AB, Schrama, LH and Schotman, P 1991. Role of the growth-associated protein B-50/GAP-43 in neuronal plasticity. Molecular Neurobiology 5, 61–85.Google Scholar
Herzog, K, Brockhan-Lüdemann, M, Kaske, M, Beindorff, N, Paul, V, Niemann, H and Bollwein, H 2010. Luteal blood flow is a more appropriate indicator for luteal function during the bovine estrous cycle than luteal size. Theriogenology 73, 691–697.Google Scholar
Holman, A, Thompson, J, Routly, JE, Cameron, J, Jones, DN, Grove-White, D, Smith, RF and Dobson, H 2011. Comparison of oestrus detection methods in dairy cattle. The Veterinary Record 169, 47.Google Scholar
Hurnik, JF, King, GJ and Robertson, HA 1975. Estrous and related behaviour in postpartum Holstein cows. Applied Animal Ethology 2, 55–68.Google Scholar
Inchaisri, C, Jorritsma, R, Vos, PLAM, Van der Weijden, GC and Hogeveen, H 2010. Economic consequences of reproductive performance in dairy cattle. Theriogenology 74, 835–846.Google Scholar
Jasoni, CL, Todman, MG, Han, SK and Herbison, AE 2005. Expression of mRNAs encoding receptors that mediate stress signals in gonadotropin-releasing hormone neurons of the mouse. Neuroendocrinology 82, 320–328.Google Scholar
Jones, KJ, Harrington, CA, Chikaraishi, DM and Pfaff, DW 1990. Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes. Journal of Neuroscience 10, 1513–1521.Google Scholar
Kalamatianos, T, Kalló, I, Goubillon, ML and Coen, CW 2004. Cellular expression of V1a vasopressin receptor mRNA in the female rat preoptic area: effects of oestrogen. Journal of Neuroendocrinology 16, 525–533.Google Scholar
Katz, LS 2007. Sexual behavior of domesticated ruminants. Hormones and Behavior 52, 56–63.CrossRefGoogle ScholarPubMed
Kelly, MJ and Qiu, J 2010. Estrogen signaling in hypothalamic circuits controling reproduction. Brain Research 1364, 44–52.Google Scholar
Kommadath, A 2012. Genomic regulation of oestrous behaviour in dairy cattle. Thesis PhD, Wageningen University, The Netherlands.Google Scholar
Kommadath, A, Te Pas, MFW and Smits, MA 2013. Gene co-expression network analysis identifies genes and biological processes shared among anterior pituitary and brain areas that affect estrous behavior in dairy cow. Journal of Dairy Science 96, 2583–2595.Google Scholar
Kommadath, A, Woelders, H, Beerda, B, Mulder, HA, De Wit, AAC, Veerkamp, RF, Te Pas, MFW and Smits, MA 2011. Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows. BMC Genomics 12, 200.CrossRefGoogle ScholarPubMed
Kommadath, A, Mulder, HA, De Wit, AAC, Woelders, H, Smits, MA, Beerda, B, Veerkamp, RF, Frijters, ACJ and Te Pas, MFW 2010. Gene expression patterns in anterior pituitary associated with quantitative measure of oestrous behaviour in dairy cows. Animal 4, 1297–1307.Google Scholar
Kow, LM and Pfaff, DW 2004. The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions. Proceedings of the National Academy of Sciences of the United States of America 101, 12354–12357.Google Scholar
Kuiper, GGJM, Carlsson, B, Grandien, K, Enmark, E, Häggblad, J, Nilsson, S and Gustafsson, JÅ 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138, 863–870.Google Scholar
Kyle, SD, Callahan, CJ and Allrich, RD 1992. Effect of progesterone on the expression of estrus at the first postpartum ovulation in dairy cattle. Journal of Dairy Science 75, 1456–1460.Google Scholar
Leng, G, Meddle, SL and Douglas, AJ 2008. Oxytocin and the maternal brain. Current Opinion in Pharmacology 8, 731–734.Google Scholar
Levine, JE, Chapell, PE, Schneider, JS, Sleiter, NC and Szabo, M 2001. Progesterone receptors as neuroendocrine integrators. Frontiers in Neuroendocrinology 22, 69–106.Google Scholar
Lopez, H, Bunch, TD and Shipka, MP 2002. Estrogen concentrations in milk at estrus and ovulation in dairy cows. Animal Reproduction Science 72, 37–46.Google Scholar
Lopez, H, Satter, LD and Wiltbank, MC 2004. Relationship between level of milk production and estrous behavior of lactating dairy cows. Animal Reproduction Science 81, 209–223.CrossRefGoogle ScholarPubMed
Lyimo, ZC, Nielen, M, Ouweltjes, W, Kruip, TAM and Van Eerdenburg, FJCM 2000. Relationship among estradiol, cortisol and intensity of estrous behavior in dairy cattle. Theriogenology 53, 1783–1795.Google Scholar
Mani, SK and Blaustein, JD 2012. Neural progestin receptors and female sexual behavior. Neuroendocrinology 96, 152–161.Google Scholar
Marsh, DJ, Weingarth, DT, Novi, DE, Chen, HY, Trumbauer, ME, Chen, AS, Guan, X-M, Jiang, MM, Feng, Y, Camacho, RE, Shen, Z, Frazier, EG, Yu, H, Metzger, JM, Kuca, SJ, Shearman, LP, Gopal-Truter, S, MacNeil, DJ, Strack, AM, MacIntyre, DE, Van der Ploeg, LHT and Qian, S 2002. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proceedings of the National Academy of Sciences of the United States of America 99, 3240–3245.Google Scholar
Martins, AC, Mollo, MR, Bastos, MR, Guardieiro, MM and Sartori, R 2008. Serum hormone concentrations of zebu cows under low and high feed intake. Pesquisa Agropecuária Brasileira Brasília 43, 243–247.Google Scholar
McCarthy, MM, McDonald, CH, Brooks, PJ and Goldman, D 1997. An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. Physiology & Behavior 60, 1209–1215.Google Scholar
Meier, S, Roche, JR, Kolver, ES, Verkerk, GA and Boston, RC 2009. Comparing subpopulations of plasma progesterone using cluster analyses. Journal of Dairy Science 92, 1460–1468.Google Scholar
Millington, GWM 2007. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutrition & Metabolism 4, 18.Google Scholar
Mitra, R, Ferguson, D and Sapolsky, RM 2009. SK2 potassium channel over-expression in basolateral amygdala reduces anxiety, stress-induced corticosterone and dendritic arborization. Molecular Psychiatry 14, 847–855.Google Scholar
Mong, JA and Pfaff, DW 2004. Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors. Molecular Psychiatry 9, 550–556.Google Scholar
Parr, RA, Davis, IF, Miles, MA and Squires, TJ 1993a. Feed intake affects metabolic clearance rate of progesterone in sheep. Research in Veterinary Science 55, 306–310.Google Scholar
Parr, RA, Davis, IF, Miles, MA and Squires, TJ 1993b. Liver blood flow and metabolic clearance rate of progesterone in sheep. Research in Veterinary Science 55, 311–316.Google Scholar
Patisaul, HB, Scordalakes, EM, Young, LJ and Rissman, EF 2003. Oxytocin, but not oxytocin receptor, is regulated by oestrogen receptor β in the female mouse hypothalamus. Journal of Neuroendocrinology 15, 787–793.Google Scholar
Pawluski, JL, Brummelte, S, Barha, CK, Crozier, TM and Galea, LAM 2009. Effects of steroid hormones on neurogenesis in the hippocampus of the adult female rodent during the estrous cycle, pregnancy, lactation and aging. Frontiers in Neuroendocrinology 30, 343–357.Google Scholar
Pfaff, D 2005. Hormone-driven mechanisms in the central nervous system facilitate the analysis of mammalian behaviours. Journal of Endocrinology 184, 447–453.CrossRefGoogle ScholarPubMed
Pfaff, D, Waters, E, Khan, Q, Zhang, X and Numan, M 2011. Estrogen receptor-initiated mechanisms causal to mammalian reproductive behaviors. Endocrinology 152, 1209–1217.Google Scholar
Rabiee, AR, Macmillan, KL and Schwarzenberger, F 2001. The effect of level of feed intake on progesterone clearance rate by measuring faecal progesterone metabolites in grazing dairy cows. Animal Reproduction Science 67, 205–214.Google Scholar
Reames, PS, Hatler, TB, Hayes, SH, Ray, DL and Silvia, WJ 2011. Differential regulation of estrous behavior and luteinizing hormone secretion by estradiol-17β in ovariectomized dairy cows. Theriogenology 75, 233–240.CrossRefGoogle ScholarPubMed
Rege, TA and Hagood, JS 2006. Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB Journal 20, 1045–1054.Google Scholar
Rex, A, Marsden, CA and Fink, H 1997. Cortical 5-HT-CCK interactions and anxiety-related behaviour of guinea-pigs: a microdialysis study. Neuroscience Letters 228, 79–82.Google Scholar
Rhodes, FM, McDougall, S, Burke, CR, Verkerk, GA and MacMillan, KL 2003. Treatment of cows with an extended postpartum anestrous interval. Journal of Dairy Science 86, 1876–1894.Google Scholar
Roche, JF 2006. The effect of nutritional management of the dairy cow on reproductive efficiency. Animal Reproduction Science 96, 282–296.CrossRefGoogle ScholarPubMed
Roelofs, J, López-Gatius, F, Hunter, RHF, Van Eerdenburg, FJCM and Hanzen, Ch 2010. When is a cow in estrus? Clinical and practical aspects. Theriogenology 74, 327–344.Google Scholar
Roelofs, JB, Van Eerdenburg, FJCM, Soede, NM and Kemp, B 2005. Various behavioral signs of estrous and their relationship with time of ovulation in dairy cattle. Theriogenology 63, 1366–1377.Google Scholar
Rougon, G and Hobert, O 2003. New insights into the diversity and function of neuronal immunoglobulin superfamily molecules. The Annual Review of Neuroscience 26, 207–238.Google Scholar
Sangsritavong, S, Combs, DK, Sartori, R, Armentano, LE and Wiltbank, MC 2002. High feed intake increases liver blood flow and metabolism of progesterone and estradiol-17β in dairy cattle. Journal of Dairy Science 85, 2831–2842.Google Scholar
Sartori, R, Haughian, JM, Shaver, RD, Rosa, GJM and Wiltbank, MC 2004. Comparison of ovarian function and circulating steroids in estrous cycles of Holstein heifers and lactating cows. Journal of Dairy Science 87, 905–920.Google Scholar
Schober, JM and Pfaff, D 2007. The neurophysiology of sexual arousal. Best Practice & Research Clinical Endocrinology & Metabolism 21, 445–461.Google Scholar
Sokolov, BP 2007. Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies? The International Journal of Neuropsychopharmacology 10, 547–555.Google Scholar
Sousa, JC, Grandela, C, Fernández-Ruiz, J, De Miguel, R, De Sousa, L, Magalhães, AI, Saraiva, MJ, Sousa, N and Palha, JA 2004. Transthyretin is involved in depression-like behaviour and exploratory activity. Journal of Neurochemistry 88, 1052–1058.Google Scholar
Starbuck, GR and Mann, GE 2010. Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows. Reproduction in Domestic Animals 45, 283–286.Google Scholar
Takahashi, K, Yamada, M, Ohata, H, Honda, K and Yamada, M 2005. Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells. Neuroscience Letters 388, 157–162.Google Scholar
Tanaka, T, Shiina, T, Hayashi, S, Okamura, H, Kamomae, H and Kaneda, Y 2003. Estrogen receptor alpha expression in the medial preoptic area and the medial basal hypothalamus under different physiological conditions in cattle. Journal of Reproduction and Development 49, 55–60.Google Scholar
Terry-Lorenzo, RT, Inoue, M, Connor, JH, Haystead, TAJ, Armbruster, BN, Gupta, RP, Oliver, CJ and Shenolikar, S 2000. Neurofilament-L is a protein phosphatase-1-binding protein associated with neuronal plasma membrane and post-synaptic density. Journal of Biological Chemistry 275, 2439–2446.Google Scholar
Uhart, M, McCaul, ME, Oswald, LM, Choi, L and Wand, GS 2004. GABRA6 gene polymorphism and an attenuated stress response. Molecular Psychiatry 9, 998–1006.CrossRefGoogle Scholar
Uphouse, L 2000. Female gonadal hormones, serotonin, and sexual receptivity. Brain Research Reviews 33, 242–257.Google Scholar
Van Eerdenburg, FJCM, Loeffler, HSH and Van Vliet, JH 1996. Detection of oestrus in dairy cows: a new approach to an old problem. Veterinary Quarterly 18, 52–54.Google Scholar
Van Eerdenburg, FJCM, Daemen, IAJJM, Van der Beek, EM and Van Leeuwen, FW 2000. Changes in estrogen-alpha receptor immunoreactivity during the estrous cycle in lactating dairy cattle. Brain Research 880, 219–223.Google Scholar
Vasudevan, N, Kow, LM and Pfaff, D 2005. Integration of steroid hormone initiated membrane action to genomic function in the brain. Steroids 70, 388–396.Google Scholar
Walsh, SW, Williams, EJ and Evans, ACO 2011. A review of the causes of poor fertility in high milk producing dairy cows. Animal Reproduction Science 123, 127–138.Google Scholar
Wiltbank, M, Lopez, H, Sartori, R, Sangsritavong, S and Gümen, A 2006. Changes in reproductive physiology of lactating dairy cows due to elevated steroid metabolism. Theriogenology 65, 17–29.Google Scholar
Yoshida, C and Nakao, T 2005. Some characteristics of primary and secondary oestrous signs in high-producing dairy cows. Reproduction in Domestic Animals 40, 150–155.Google Scholar
Zhao, J, Quyyumi, AA, Patel, R, Zafari, AM, Veledar, E, Onufrak, S, Shallenberger, LH, Jones, L and Vaccarino, V 2009. Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene. Psychosomatic Medicine 71, 691–696.Google Scholar
Supplementary material: File

Woelders Supplementary Material

Table S1

Download Woelders Supplementary Material(File)
File 11.1 KB