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Journal of Integrative Agriculture  2017, Vol. 16 Issue (07): 1558-1565    DOI: 10.1016/S2095-3119(16)61520-4
Animal Science · Veterinary Science Advanced Online Publication | Current Issue | Archive | Adv Search |
Association of CYP19A1 gene polymorphisms with reproductive traits in pigs
ZHOU Rong1, 2, YANG Ya-lan2, LIU Ying2, CHEN Qi-mei3, CHEN Jie1, LI Kui1, 2
1 Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, P.R.China
2 Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation, Ministry of Agriculture/Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China
3 Shandong Lansi Seeds Industry Co., Ltd., Rizhao 276800, P.R.China
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Abstract      Porcine reproductive traits are characterized by low heritability, making improvement by traditional selective breeding rather difficult. Molecular breeding offers powerful approaches to overcome previous limitations and is expected to generate economic benefits via progress in pig breeding. Cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1) gene is a key enzyme of estradiol biosynthesis that plays an important role in the establishment of gestation and maintenance of pregnancy. In this study, the sequence and structure characteristics of the porcine CYP19A1 gene was analyzed and expression patterns of CYP19A1 in different tissues of adult female pigs were detected. Fourteen single-nucleotide polymorphisms (SNPs) in the exons and introns of porcine CYP19A1 were identified and genotyped using the Sequenom MassARRAY platform, after which the allele frequency of each SNP was analyzed. The association between CYP19A1 SNPs and litter size and piglet birth weight was assessed in a crossbred pig population (n=375). The expression pattern of CYP19A1 revealed that it was highly expressed in the ovary, spleen, and uterus and lowly expressed in the other tissues. Moreover, one SNP, rs341891833, was significantly associated with piglet birth weight during the multiparity period (P<0.01). We concluded that CYP19A1 could be used as a candidate molecular marker in breeding aimed at rapid improvement of the reproductive characteristics of pigs.  
Keywords:  CYP19A1        pig        reproduction        birth weight        single nucleotide polymorphism  
Received: 29 May 2016   Accepted:

This work was supported by the National Natural Science Foundation of China (31501931), the 948 Program of China (2011-G11), and the Agricultural Science and Technology Innovation Program, China (ASTIP-IAS05).

Corresponding Authors:  Correspondence CHEN Jie, Tel/Fax: +86-25-84396347, E-mail:; LI Kui, Tel/Fax: +86-10-62813822, E-mail:   
About author:  ZHOU Rong, E-mail:;

Cite this article: 

ZHOU Rong, YANG Ya-lan, LIU Ying, CHEN Qi-mei, CHEN Jie, LI Kui . 2017. Association of CYP19A1 gene polymorphisms with reproductive traits in pigs. Journal of Integrative Agriculture, 16(07): 1558-1565.

Akçurin S, Türkkahraman D, Kim W Y, Durmaz E, Shin J G, Lee S J. 2016. A novel null mutation in P450 aromatase gene (CYP19A1) associated with the development of hypoplastic ovaries in humans. Journal of Clinical Research in Pediatric Endocrinology, 8, 205–210.

Albrecht B A, Daels P F. 1997. Immunolocalization of 3 beta-hydroxysteroid dehydrogenase, cytochrome P450 17 alpha-hydroxylase/17,20-lyase and cytochrome P450 aromatase in the equine corpus luteum of dioestrus and early pregnancy. Journal of Reproduction and Fertility, 111, 127–133.

Bao B, Garverick H A. 1998. Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: A review. Journal of Animal Science, 76, 1903–1921.

Bershtein L M. 1997. Molecular-genetic aspects of estrogen production. Aromatase gene. Molekulyarnaya Biologiya,  31, 773–777.

Chiang E F, Yan Y L, Guiguen Y, Postlethwait J, Chung B C. 2001. Two Cyp19  (P450 aromatase) genes on duplicated zebrafish chromosomes are expressed in ovary or brain. Molecular Biology and Evolution, 18, 542–550.

Conley A, Corbin J, Smith T, Hinshelwood M, Liu Z, Simpson E.1997. Porcine aromatases: studies on tissue-specific, functionally distinct isozymes from a single gene? Journal of Steroid Biochemistry and Molecular Biology, 61, 407–413.

Conley A J, Corbin C J, Hinshelwood M M, Liu Z, Simpson E R, Ford J J, Harada N. 1996. Functional aromatase expression in porcine adrenal gland and testis. Biology of Reproduction, 54, 497–505.

Coban N, Onat A, Guclu-Geyik F, Can G, Erginel-Unaltuna N. 2015. Sex- and obesity-specific association of aromatase (CYP19A1) gene variant with apolipoprotein B and hypertension. Archives of Medical Research, 46, 564–571.

Corbin C J, Berger T, Ford J J, Roselli C E, Sienkiewicz W, Trainor B C, Roser J F, Vidal J D, Harada N, Conley A J. 2009. Porcine hypothalamic aromatase cytochrome P450: isoform characterization, sex-dependent activity, regional expression, and regulation by enzyme inhibition in neonatal boars. Biology of Reproduction, 81, 388–395.

Elbrecht A, Smith R G. 1992. Aromatase enzyme activity and sex determination in chickens. Science, 255, 467–470.

Fitko R, Kucharski J, Szlezyngier B, Jana B. 1996. The concentration of GnRH in hypothalamus, LH and FSH in pituitary, LH, PRL and sex steroids in peripheral and ovarian venous plasma of hypo- and hyperthyroid, cysts-bearing gilts. Animal Reproduction Science, 45, 123–138.

Freking B A, Leymaster K A, Vallet J L, Christenson R K. 2007. Number of fetuses and conceptus growth throughout gestation in lines of pigs selected for ovulation rate or uterine capacity. Journal of Animal Science, 85, 2093–2103.

Gabriel S, Ziaugra L, Tabbaa D. 2009. SNP genotyping using the sequenom MassARRAY iPLEX Platform. Current Protocols in Human Genetics. No. 60. Chapter 2, Unit 2.12.

Gama L L, Johnson R K. 1993. Changes in ovulation rate, uterine capacity, uterine dimensions, and parity effects with selection for litter size in swine. Journal of Animal Science, 71, 608–617.

Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins M R, Appel R D, Bairoch A. 2005. Protein identification and analysis tools on the ExPASy server. In: Walker J M, ed., The Proteomics Protocols Handbook. Humana Press, Totowa, NJ.

George F W, Ojeda S R. 1987. Vasoactive intestinal peptide enhances aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone. Proceedings of the National Academy of Sciences of the United States of America, 84, 5803–5807.

Graham-Lorence S, Amarneh B, White R E, Peterson J A, Simpson E R. 1995. A three-dimensional model of aromatase cytochrome P450. Protein Science, 4, 1065–1080.

Guo Y Y, Zhang L C, Wang L X, Liu W Z. 2015. Genome-wide association study for rib eye muscle area in a Large White×Minzhu F2 pig resource population. Journal of Integrative Agriculture, 12, 2590–2597.

Hess M F, Roser J F. 2004. Immunocytochemical localization of cytochrome P450 aromatase in the testis of prepubertal, pubertal, and postpubertal horses. Theriogenology, 61, 293–299.

Hillier S G, Whitelaw P F, Smyth C D. 1994. Follicular oestrogen synthesis: The ‘two-cell, two-gonadotrophin’ model revisited. Molecular and Cellular Endocrinology, 100, 51–54.

Horton P, Park K J, Obayashi T, Fujita N, Harada H, Adams-Collier C J, Nakai K. 2007. WoLF PSORT: Protein localization predictor. Nucleic Acids Research, 35, W585–W587.

Kanda S, Tsuchiya N, Narita S, Inoue T, Huang M, Chiba S, Akihama S, Saito M, Numakura K, Tsuruta H, Satoh S, Saito S, Ohyama C, Arai Y, Ogawa O, Habuchi T. 2015. Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival. International Journal of Cancer, 136, 74–82.

Krogh A, Larsson B È, Von Heijne G, Sonnhammer E L. 2001. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. Journal of Molecular Biology, 305, 567–580.

Kwon J Y, McAndrew B J, Penman D J. 2001. Cloning of brain aromatase gene and expression of brain and ovarian aromatase genes during sexual differentiation in genetic male and female Nile tilapia Oreochromis niloticus. Molecular Reproduction and Development, 59, 359–370.

Liu L Q, Li F E, Deng C Y, Zuo B, Zheng R, Xiong Y Z. 2009. Polymorphism of the pig 17beta-hydroxysteroid dehydrogenase type1 (HSD17B1) gene and its association with reproductive traits. Animal Reproduction Science, 114, 318–323.

Logan K A, Juengel J L, McNatty K P. 2002. Onset of steroidogenic enzyme gene expression during ovarian follicular development in sheep. Biology of Reproduction, 66, 906–916.

Long J R, Kataoka N, Shu X O, Wen W, Gao YT, Cai Q, Zheng W. 2006. Genetic polymorphisms of the CYP19A1 gene and breast cancer survival. Cancer Epidemiology, Biomarkers & Prevention, 15, 2115–2122.

Mazzuca F, Botticelli A, Mazzotti E, La Torre M, Borro M, Marchetti L, Maddalena C, Gentile G, Simmaco M, Marchetti P. 2016. CYP19A1 genetic polymorphisms rs4646 and osteoporosis in patients treated with aromatase inhibitor-based adjuvant therapy. Eurasian Journal of Medicine, 48, 10–14.

Niu B Y, Lan X M, Yan X H, Di S W, Wang Y, Li H T, Xiong Y Z, Wang X B. 2013. Characterization of porcine matrix metalloproteinase 23 (pMMP-23) gene and its association with litter size traits. Journal of Integrative Agriculture, 12, 103–109.

Oh J N, Hwang J Y, Choi K H, Lee C K. 2016. Treatment of aromatase (CYP19A1) inhibitor reduces fertility in porcine sperm. Zygote, 24, 98–106.

Quirke L D, Juengel J L, Tisdall D J, Lun S, Heath D A, McNatty K P. 2001. Ontogeny of steroidogenesis in the fetal sheep gonad. Biology of Reproduction, 65, 216–228.

Rago V, Aquila S, Panza R, Carpino A. 2007. Cytochrome P450arom, androgen and estrogen receptors in pig sperm. Reproductive Biology and Endocrinology, 5, 23.

Redler S, Birch M P, Drichel D, Dobson K, Brockschmidt F F, Tazi-Ahnini R, Giehl K A, Kluck N, Kruse R, Lutz G, Wolff H, Becker T, Nöthen M M, Messenger A G, Betz R C. 2011. Investigation of variants of the aromatase gene (CYP19A1) in female pattern hair loss. The British Journal of Dermatology, 165, 703–705.

Rui W, Sheng Y, Hu R, Miao Y, Han Y, Guo X, Qi S, Xu F, Xu J, Yang Q. 2015. Association of single nucleotide polymorphisms in the CYP19A1 gene with female pattern hair loss in a Chinese population. Dermatology, 231, 239–244.

Shao X, Cai J, Zheng Y, Wang J, Feng J, Huang Y, Shi L, Chen Z, Guo Y, Wang X. 2015. S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer. International Journal of Clinical and Experimental Pathology, 8, 5309–5317.

Simpson E R, Kilgore M W, Mahendroo M S, Means G D, Corbin C J, Mendelson C R. 1992. Regulation of human aromatase cytochrome P450 gene expression. Journal of Steroid Biochemistry and Molecular Biology, 43, 923–930.

Simpson E R, Mahendroo M S, Means G D, Kilgore M W, Hinshelwood M M, Graham-Lorence S, Amarneh B, Ito Y, Fisher C R, Michael M D. 1994. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocrine Reviews, 15, 342–355.

Spotter A, Distl O. 2006. Genetic approaches to the improvement of fertility traits in the pig. The Veterinary Journal, 172, 234–247.

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. 2011. MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular Biology and Evolution, 28, 2731–2739.

Tao M H, Cai Q, Zhang Z F, Xu W H, Kataoka N, Wen W, Xiang Y B, Zheng W, Shu X O. 2007. Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in Chinese women. Cancer Epidemiology, Biomarkers & Prevention, 16, 943–949.

Thompson D J, O’Mara T A, Glubb D M, Painter J N, Cheng T , Folkerd E, Doody D, Dennis J, Webb P M, Gorman M, Martin L, Hodgson S, Michailidou K, Tyrer J P, Maranian M J, Hall P, Czene K, Darabi H, Li J M, Fasching P A, et al. 2016. CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer. Endocrine-related Cancer, 23, 77–91.

Weng Q, Medan M S, Watanabe G, Tsubota T, Tanioka Y, Taya K. 2005. Immunolocalization of steroidogenic enzymes P450scc, 3betaHSD, P450c17, and P450arom in Gottingen miniature pig testes. Journal of Reproduction and Development, 51, 299–304.

Yip L, Zaloumis S, Irwin D, Severi G, Hopper J, Giles G, Harrap S, Sinclair R, Ellis J. 2009. Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. British Journal of Dermatology, 161, 289–294.

Zhang T, Wang L G, Shi H B, Yan H, Zhang L C, Liu X, Pu L, Liang J, Zhang Y B, Zhao K B, Wang L X. 2016. Heritabilities and genetic and phenotypic correlations of litter uniformity and litter size in Large White sows. Journal of Integrative Agriculture, 15, 848–854.
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