Non classical function of vitamin d – influence on reproductive health, puberty and fertility

Elina Chaykivska, Zlata Chaykivska

Abstract


In the past few years, there has been growing appreciation for the many roles of vitamin D and its active metabolites in a large number of tissues. Most tissues in the body, not just those participating in the classic action of vitamin D such as bone, kidney and gut, have receptors (VDR) for the active form of vitamin D – 1,25 dihydroxyvitamin D. The recent data on vitamin D from retrospective, prospective observational studies, case-control and experimental studies confirm the essential role of vitamin D in a variety of physiological functions. Last time there has been growing interest in this substance observed in the scientific researches and biomedical literature, due to findings which demonstrate a vitamin D deficiency status in the population.
This review is an analysis of the association between the vitamin D and the female and male reproduction and fertility. We highlight the latest findings from medical trials on vitamin D during last years. The aim of this article is to understand how vitamin D affects the female and male fertility. Vitamin D is a hormone which controls nearly 1/3 of human and mice genome, over 200 genes in a human body, including those responsible for cell cycle control: proliferation, differentiation, apoptosis. Apart from basic functions, which are maintaining calcium-phosphoric balance, vitamin D takes active part in process of cell proliferation, epidermal keratinocyte differentiation, immune system stimulation, insulin secretion, brain metabolism, adipocytes function, puberty, reproduction and fertility. The vitamin D receptors (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. VDR knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Assuming that 30 ng/ml (75 nmol/l) is a lower limit of normal concentration of 25(OH)D3 in serum, the number of people with vitamin D deficit equals about 1 billion worldwide.


Keywords


vitamin D; fertility; puberty; vitamin D receptors; reproductive health

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References


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Mayer E. «The curative value of light: sunlight and sun lamp in health and disease.» Witefish, MT Kessinger Publishing (1932).

McCollum E.V., Simmonds N., Becker J.E., Shipley P.G. «Studies on experimental rickets. XXI. An experimental demonstration of the existence of a vitamin which promotes calcium deposition.» J Biol Chem, 53(1922):293-312.

Girgis C.H.M., Roderick J., Clifton-Bligh, Hamrick M., Holick M., Gunton J. «The roles of vitamin D in skeletal muscle: form, function, metabolism.» End Rev, 34(1) (2013):33-83.

Bouillon R., Carmeliet G., Verlinden L., van Etten E., Verstuyf A., Luderer H., Lieben L., Mathieu C., Demay M. «Vitamin D and human health: lessons from vitamin D receptor null mice.» Endocrine Reviews, 29(6) (2008): 726-776.

Keisala T., Minasyan A., Lou Y.R., Zou J., Kalueff A.V., Pyykko I., Tuohimaa P. «Premature aging in vitamin D receptor mutant mice.» J Steroid Mol Biol, 115(3-5) (2009):91-7.

Whitfield G.K., Dang H.T., Schhluter S.F., Bernstein R.M., Bunag T., Manzon L.A., Hsieh G., Dominguez C.E., Youson J.H., Haussler M.R., Marchalonis J.J. «Clonning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth.» Endocrinology, 144(2003):2704-2716.

van Schoor N.M., Lips P. «Worldwide vitamin D status.» Best Pract res Clin Endocrinol Metab, 25(2011):671-680.

Cooke N.E., Haddad J.G. «Vitamin D binding protein (Gc-globulin).» Endoct Rev, 10(1989):294-307.

Rosen C.J., Adams J.S., Bikle D.D., Black D.M., Demay M.B., Manson J.E., Murad M.H., Kovacs C.S. «The nonsceletal effects of vitamin D; an Endocrine society scientific statement.» Endocrine Rev, 33(3)(2012):456-92.

Halloran B.P., DeLuca H.F. «Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat.» J Nurt, 110(1980):1573-1580.

Kinuta K., Tanaka H., Moriwake T., Aya K., Kato S., Seino Y.«Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads.» Endocrinology, 141(2000): 1317-1324.

Bagheri M., Phil M., Abdi Rad I., Jazani Hosseini N., Nanbakhsh F. Int J Fertil Steril, 7(2) (2013):116-121.

Lerchbaum E., Rabe T. «Vitamin D and female fertility.» Curr Opin Obstet Gyn, 26(3) (2014):145-150.

Dicken C.L., Israel D.D., Davis J.B., Sun Y., Shu J., Hardin J., Neal-Perry G. «Peripubertal vitamin D3 deficiency delays puberty and disrupts the estrous cycle in adult female mice.» Biology of Reprod, 87(2) (2012):51, 1-12.

Eyles D.W., Smith S., Kinobe R., Hewison M., McGrath J.J. «Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.» J Chem Neuroanat, 29(1) (2005):21-30.

Walbert T., Jirikowski G.F., Prufer K. «Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the limbic system of rat.» Horm Metab Res, 33(9) (2001):525-531.

Walker D.M., Jueger T.E., Gore A.C. «Developmental profiles of neuroendocrine gene expression in the preoptic area of male rats.» Endocrinolgy, 150(5) (2009):2308-2316.

Alemzadeh R., Kichler J., Babar G., Calhoun M. «Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season.» Metabolism, 57(2) (2008):183-191.

Bradlee M.L., Singer M.R., Qureshi M.M., Moore L.L. «Food group intake and central obesity among children and adolescents in the Third National Health and Nutrition Examination Survey (NHANES III).» Public Health Nutr (2009):1-9.

Ma Y.J., Hill D.F., Creswick K.E., Costa M.E., Cornea A., Lioubin M.N., Plowman G.D., Ojeda S.R. «Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development.» J Neuroscie, 19(22) (1999):9913-9929.

Ojeda S.R., Lomniczi A., Loche A., Matagne V., Kaidar G., Sandau U.S., Dissen G.A. «The transcriptional control of female puberty.» Brain Res, 1364(2010):164-174.

Gezen-Ak D., Dursun E., Yilmazer S. «The effects of vitamin D receptor silecing on the expression of LVSCC-A1C and the release of NGF in cortical neurons.» PLoS One, 6(3) (2011):e17553.

Malinina E., Druzin M., Johansson S. «Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca2+ channels in the rat medial preoptic nucleus.» J Neurophysiol, 104(1):200-209.

Morteza Bagheri, Isa Abdi Rad, Nima Hosseini Jazani, Fariba Nanbakhsh Int J fertile Steril, 7(2) (2013):166-121.

Rajnzad F., Mahban A., Shemirani A.I., Mahmoudi T., Vahedi M., Nikzamir A., Zari M.R. «Influence of gene variants related to calcium homeostasis on biochemical parameters of women polycystic ovary syndrome.» J Assist Reprod Genet, 28(3) (2011):225-32 .

Brannon P.M., Picciano M.F. «Vitamin D in pregnancy and lactation in humans.» Annu Rev Nutr, 31(2011):89-115.

Vigano P., Lattuada D., Mangioni S., Ermellino L., Vignali M., Caporizzo E., Panina-Bordignon P., Besozzi M., Di Blasio A.M. «Cykling and early pregnant endometrium as a site of regulated expression of the vitamin D system.» J Mol Endocrinol, 36(3) (2006):415-424.

Holly R. Harris, Chavarro J.E., Missmer S.A. «Dairy-food, calcium, magnesium and vitamin D intake and endometriosis: a prospective cohort study.» An J Epidemiol, 177(5) (2013):420-430.

Bikle D. «Nonclassical actions of vitamin D.», 94(1) (2009):26-34.

Stewart E.A. «Uterine fibroids.» Lancet, 357(2001):293-298.

Halder S.K., Goodwin J.S., Al-Hendy A. «1,25-dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells.» J Clin Endocrinol Metab, 96: E754-E762.

Ding L., Xu J., Luo X., Chegini N. «Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/extracellulary regulated kinase and differentially regulate fibronectine, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells.» J Clin Endocrinol Metab, 89(2004):5549-5557.

Veldman C.M., Cantorna M.T., DeLuca H.F. «Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system.» Arch Biochem Biophys, 374(2000):334-338.

Cutolo M., Paolino S., Sulli A., Smith V., Pizzorni C., Seriolo B. «Vitamin D, steroid hormones, and autoimmunity.» Ann NY Acad Sci, 2014, doi 10.1111.

Stoffels K., Overbergh L., Giulietti A., Verlinden L., Bouillon R., Mathieu C. «Immune regulation of 1,25-dihydroxyvitamin- D3-1a-hydroxylase in human monocytes.» J Bone Miner Res, 21(2006):37-47.

Hasan Z., Salahuddin N., Rao N., Aqeel M., Mahmood F., Ali F., Asraf M., Rahman F., Mahmood S., Islam M., Dildar B., Anwer T., Oiighor F., Sharif N., Ullah A.R. «Change in serum CXCL 10 during anti-tuberculosis treatment depends on vitamin D status.» Int J Tuber Lung Dis, 18(4) (2014):466-9.

Borella E., Nesher G., Israeli E., Shoenfeld Y. «Vitamin D – a new anti-infective agent?» Ann NY Acad Sci, 2014, doi:10.1111.

Ustianowski A., Shaffer R., Collin S., Wilkinson R.J., Davison R.N. «Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London.» J Infect, 50(2005):432-437.

Norman A.W., Frankel J.B., Heldt A.M., Grodsky G.M. «Vitamin D deficiency inhibits pancreatic secretion of insulin.» Science, 209:823-825.

Rabinovitch A., Suarez-Pinzon W.L., Sooy K., Strynadka K., Christakos «Expression of calbindin-D-28k in pancreatic islet beta-cell line protects against cytokine-induced apoptosis and necrosis.» Endocrinology, 142(2001):3649-3655.

Mathieu C., Badenhoop K. «Vitamin D and type I diabetes mellitus: state of art.» Trends Endocrinol Metab, 16(2005):261-6.

Aqarwal N., Mithal A., Kaur P., Dhingra V., Godbole M.M., Shukla M. «Vitamin D and insulin resistance in postmenopausal Indian women.» Ind Endocrin Metab, 18(1) (2014): 89-93.

Garcion E., Wion-Barbot N., Montero-Menei C.N., Berger F., Wion D. «New clues about vitamin D functions in the nervous system.» Trends Endocrinol Metab, 13(2002):100-105.

McGrath J., Eyles D., Mowry B., Yolken R., Buka S. «Low maternal vitamin D as risk factor for schizophrenia: a pilot study using banked sera.» Schizophr Res, 63(2003)73-78.

Przybelski R.J., Binkley N.C. «Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function.» Arch Biochem Biophys, 460:202-205.

Duan X.Y., Jia F.Y., Jiang H.Y. «Relationship between vitamin D and autism spectrum disorder.» Zhongguo Dang Dai Er Ke Za Zhi, 15(8) (2013):698-702.

Patrick R.P., Ames B.N. «Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.» FASEB J( 2014).

Richards J.B., Valdes A.M., Gardner J.P., Paximadas D., Kimura M., Nessa A., Lu X., Surdulescu G.L., Swaminathan R., Spector T.D., Aviv A.«Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women.» Am J Clin Nutr, 86(2007):1420-5.

Liu J.J., Prescott J., Giovannucci E., Hankinson S.E., Rosner B., Han J., De Vivo I. «Plasma vitamin D biomarkers and leukocyte telomere length.» Am J Epidemiol, 15;177(12) (2013):1411-7.


GOST Style Citations


Monderson F. «The majestry of Egyptian gods an temples: a book of Egyptian poems.» Bloomington, IN: Authorhouse (2007).

Mayer E. «The curative value of light: sunlight and sun lamp in health and disease.» Witefish, MT Kessinger Publishing (1932).

McCollum E.V., Simmonds N., Becker J.E., Shipley P.G. «Studies on experimental rickets. XXI. An experimental demonstration of the existence of a vitamin which promotes calcium deposition.» J Biol Chem, 53(1922):293-312.

Girgis C.H.M., Roderick J., Clifton-Bligh, Hamrick M., Holick M., Gunton J. «The roles of vitamin D in skeletal muscle: form, function, metabolism.» End Rev, 34(1) (2013):33-83.

Bouillon R., Carmeliet G., Verlinden L., van Etten E., Verstuyf A., Luderer H., Lieben L., Mathieu C., Demay M. «Vitamin D and human health: lessons from vitamin D receptor null mice.» Endocrine Reviews, 29(6) (2008): 726-776.

Keisala T., Minasyan A., Lou Y.R., Zou J., Kalueff A.V., Pyykko I., Tuohimaa P. «Premature aging in vitamin D receptor mutant mice.» J Steroid Mol Biol, 115(3-5) (2009):91-7.

Whitfield G.K., Dang H.T., Schhluter S.F., Bernstein R.M., Bunag T., Manzon L.A., Hsieh G., Dominguez C.E., Youson J.H., Haussler M.R., Marchalonis J.J. «Clonning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth.» Endocrinology, 144(2003):2704-2716.

van Schoor N.M., Lips P. «Worldwide vitamin D status.» Best Pract res Clin Endocrinol Metab, 25(2011):671-680.

Cooke N.E., Haddad J.G. «Vitamin D binding protein (Gc-globulin).» Endoct Rev, 10(1989):294-307.

Rosen C.J., Adams J.S., Bikle D.D., Black D.M., Demay M.B., Manson J.E., Murad M.H., Kovacs C.S. «The nonsceletal effects of vitamin D; an Endocrine society scientific statement.» Endocrine Rev, 33(3)(2012):456-92.

Halloran B.P., DeLuca H.F. «Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat.» J Nurt, 110(1980):1573-1580.

Kinuta K., Tanaka H., Moriwake T., Aya K., Kato S., Seino Y.«Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads.» Endocrinology, 141(2000): 1317-1324.

Bagheri M., Phil M., Abdi Rad I., Jazani Hosseini N., Nanbakhsh F. Int J Fertil Steril, 7(2) (2013):116-121.

Lerchbaum E., Rabe T. «Vitamin D and female fertility.» Curr Opin Obstet Gyn, 26(3) (2014):145-150.

Dicken C.L., Israel D.D., Davis J.B., Sun Y., Shu J., Hardin J., Neal-Perry G. «Peripubertal vitamin D3 deficiency delays puberty and disrupts the estrous cycle in adult female mice.» Biology of Reprod, 87(2) (2012):51, 1-12.

Eyles D.W., Smith S., Kinobe R., Hewison M., McGrath J.J. «Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.» J Chem Neuroanat, 29(1) (2005):21-30.

Walbert T., Jirikowski G.F., Prufer K. «Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the limbic system of rat.» Horm Metab Res, 33(9) (2001):525-531.

Walker D.M., Jueger T.E., Gore A.C. «Developmental profiles of neuroendocrine gene expression in the preoptic area of male rats.» Endocrinolgy, 150(5) (2009):2308-2316.

Alemzadeh R., Kichler J., Babar G., Calhoun M. «Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season.» Metabolism, 57(2) (2008):183-191.

Bradlee M.L., Singer M.R., Qureshi M.M., Moore L.L. «Food group intake and central obesity among children and adolescents in the Third National Health and Nutrition Examination Survey (NHANES III).» Public Health Nutr (2009):1-9.

Ma Y.J., Hill D.F., Creswick K.E., Costa M.E., Cornea A., Lioubin M.N., Plowman G.D., Ojeda S.R. «Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development.» J Neuroscie, 19(22) (1999):9913-9929.

Ojeda S.R., Lomniczi A., Loche A., Matagne V., Kaidar G., Sandau U.S., Dissen G.A. «The transcriptional control of female puberty.» Brain Res, 1364(2010):164-174.

Gezen-Ak D., Dursun E., Yilmazer S. «The effects of vitamin D receptor silecing on the expression of LVSCC-A1C and the release of NGF in cortical neurons.» PLoS One, 6(3) (2011):e17553.

Malinina E., Druzin M., Johansson S. «Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca2+ channels in the rat medial preoptic nucleus.» J Neurophysiol, 104(1):200-209.

Morteza Bagheri, Isa Abdi Rad, Nima Hosseini Jazani, Fariba Nanbakhsh Int J fertile Steril, 7(2) (2013):166-121.

Rajnzad F., Mahban A., Shemirani A.I., Mahmoudi T., Vahedi M., Nikzamir A., Zari M.R. «Influence of gene variants related to calcium homeostasis on biochemical parameters of women polycystic ovary syndrome.» J Assist Reprod Genet, 28(3) (2011):225-32 .

Brannon P.M., Picciano M.F. «Vitamin D in pregnancy and lactation in humans.» Annu Rev Nutr, 31(2011):89-115.

Vigano P., Lattuada D., Mangioni S., Ermellino L., Vignali M., Caporizzo E., Panina-Bordignon P., Besozzi M., Di Blasio A.M. «Cykling and early pregnant endometrium as a site of regulated expression of the vitamin D system.» J Mol Endocrinol, 36(3) (2006):415-424.

Holly R. Harris, Chavarro J.E., Missmer S.A. «Dairy-food, calcium, magnesium and vitamin D intake and endometriosis: a prospective cohort study.» An J Epidemiol, 177(5) (2013):420-430.

Bikle D. «Nonclassical actions of vitamin D.», 94(1) (2009):26-34.

Stewart E.A. «Uterine fibroids.» Lancet, 357(2001):293-298.

Halder S.K., Goodwin J.S., Al-Hendy A. «1,25-dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells.» J Clin Endocrinol Metab, 96: E754-E762.

Ding L., Xu J., Luo X., Chegini N. «Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/extracellulary regulated kinase and differentially regulate fibronectine, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells.» J Clin Endocrinol Metab, 89(2004):5549-5557.

Veldman C.M., Cantorna M.T., DeLuca H.F. «Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system.» Arch Biochem Biophys, 374(2000):334-338.

Cutolo M., Paolino S., Sulli A., Smith V., Pizzorni C., Seriolo B. «Vitamin D, steroid hormones, and autoimmunity.» Ann NY Acad Sci, 2014, doi 10.1111.

Stoffels K., Overbergh L., Giulietti A., Verlinden L., Bouillon R., Mathieu C. «Immune regulation of 1,25-dihydroxyvitamin- D3-1a-hydroxylase in human monocytes.» J Bone Miner Res, 21(2006):37-47.

Hasan Z., Salahuddin N., Rao N., Aqeel M., Mahmood F., Ali F., Asraf M., Rahman F., Mahmood S., Islam M., Dildar B., Anwer T., Oiighor F., Sharif N., Ullah A.R. «Change in serum CXCL 10 during anti-tuberculosis treatment depends on vitamin D status.» Int J Tuber Lung Dis, 18(4) (2014):466-9.

Borella E., Nesher G., Israeli E., Shoenfeld Y. «Vitamin D – a new anti-infective agent?» Ann NY Acad Sci, 2014, doi:10.1111.

Ustianowski A., Shaffer R., Collin S., Wilkinson R.J., Davison R.N. «Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London.» J Infect, 50(2005):432-437.

Norman A.W., Frankel J.B., Heldt A.M., Grodsky G.M. «Vitamin D deficiency inhibits pancreatic secretion of insulin.» Science, 209:823-825.

Rabinovitch A., Suarez-Pinzon W.L., Sooy K., Strynadka K., Christakos «Expression of calbindin-D-28k in pancreatic islet beta-cell line protects against cytokine-induced apoptosis and necrosis.» Endocrinology, 142(2001):3649-3655.

Mathieu C., Badenhoop K. «Vitamin D and type I diabetes mellitus: state of art.» Trends Endocrinol Metab, 16(2005):261-6.

Aqarwal N., Mithal A., Kaur P., Dhingra V., Godbole M.M., Shukla M. «Vitamin D and insulin resistance in postmenopausal Indian women.» Ind Endocrin Metab, 18(1) (2014): 89-93.

Garcion E., Wion-Barbot N., Montero-Menei C.N., Berger F., Wion D. «New clues about vitamin D functions in the nervous system.» Trends Endocrinol Metab, 13(2002):100-105.

McGrath J., Eyles D., Mowry B., Yolken R., Buka S. «Low maternal vitamin D as risk factor for schizophrenia: a pilot study using banked sera.» Schizophr Res, 63(2003)73-78.

Przybelski R.J., Binkley N.C. «Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function.» Arch Biochem Biophys, 460:202-205.

Duan X.Y., Jia F.Y., Jiang H.Y. «Relationship between vitamin D and autism spectrum disorder.» Zhongguo Dang Dai Er Ke Za Zhi, 15(8) (2013):698-702.

Patrick R.P., Ames B.N. «Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.» FASEB J( 2014).

Richards J.B., Valdes A.M., Gardner J.P., Paximadas D., Kimura M., Nessa A., Lu X., Surdulescu G.L., Swaminathan R., Spector T.D., Aviv A.«Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women.» Am J Clin Nutr, 86(2007):1420-5.

Liu J.J., Prescott J., Giovannucci E., Hankinson S.E., Rosner B., Han J., De Vivo I. «Plasma vitamin D biomarkers and leukocyte telomere length.» Am J Epidemiol, 15;177(12) (2013):1411-7.





DOI: http://dx.doi.org/10.18370/2309-4117.2014.18.42-47

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