Pyridoxamine protects human granulosa cells against advanced glycation end-products-induced steroidogenesis disturbances.
Advanced glycation end-products
Granulosa cells
Pyridoxamine
Sex steroid hormone
Steroidogenic enzymes
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
12
04
2023
accepted:
31
07
2023
medline:
26
9
2023
pubmed:
29
8
2023
entrez:
29
8
2023
Statut:
ppublish
Résumé
Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM). Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3β-HSD, and 17β-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression. This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction.
Sections du résumé
BACKGROUND
BACKGROUND
Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM).
METHODS AND RESULTS
RESULTS
Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3β-HSD, and 17β-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression.
CONCLUSION
CONCLUSIONS
This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction.
Identifiants
pubmed: 37642758
doi: 10.1007/s11033-023-08723-8
pii: 10.1007/s11033-023-08723-8
doi:
Substances chimiques
Pyridoxamine
6466NM3W93
Vitamin B 6
8059-24-3
Glycation End Products, Advanced
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8537-8549Subventions
Organisme : Vice-Chancellor for Research, Shiraz University of Medical Sciences
ID : 23078
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Andersen CY, Ezcurra D (2014) Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrinol 12:128. https://doi.org/10.1186/1477-7827-12-128
doi: 10.1186/1477-7827-12-128
pubmed: 25543693
pmcid: 4396073
Hurst BS, Merriam KS, Elliot M, Matthews ML, Marshburn PB, Usadi RS, Hurst BS (2015) A sustained elevated estradiol is not the trigger for the pre-ovulatory luteinizing hormone surge. Women’s Health Gynecol 3:10–18
Dozortsev DI, Pellicer A, Diamond MP (2020) Premature progesterone rise as a trigger of polycystic ovarian syndrome. Fertil Steril 114:943–944. https://doi.org/10.1016/j.fertnstert.2020.07.007
doi: 10.1016/j.fertnstert.2020.07.007
pubmed: 33036794
Dozortsev DI, Diamond MP (2020) Luteinizing hormone-independent rise of progesterone as the physiological trigger of the ovulatory gonadotropins surge in the human. Fertil Steril 114:191–199. https://doi.org/10.1016/j.fertnstert.2020.06.016
doi: 10.1016/j.fertnstert.2020.06.016
pubmed: 32741458
Venetis CA, Storr A, Chua SJ, Mol BW, Longobardi S, Yin X, D’Hooghe T (2023) What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis. Hum Reprod Update. https://doi.org/10.1093/humupd/dmac040
doi: 10.1093/humupd/dmac040
pubmed: 36594696
pmcid: 10152179
Lawrenz B, Melado L, Fatemi H (2018) Premature progesterone rise in ART-cycles. Reprod Biol 18:1–4
doi: 10.1016/j.repbio.2018.01.001
pubmed: 29317175
Shen C-Y, Lu C-H, Wu C-H, Li K-J, Kuo Y-M, Hsieh S-C, Yu C-L (2020) The development of Maillard reaction, and Advanced Glycation End product (AGE)-Receptor for AGE (RAGE) signaling inhibitors as Novel therapeutic strategies for patients with AGE-Related Diseases. Molecules 25:5591
doi: 10.3390/molecules25235591
pubmed: 33261212
pmcid: 7729569
Prasad C, Davis KE, Imrhan V, Juma S, Vijayagopal P (2019) Advanced Glycation End Products and Risks for Chronic Diseases: intervening through Lifestyle Modification. Am J Lifestyle Med 13:384–404. https://doi.org/10.1177/1559827617708991
doi: 10.1177/1559827617708991
pubmed: 31285723
Twarda-Clapa A, Olczak A, Białkowska AM, Koziołkiewicz M (2022) Advanced Glycation End-Products (AGEs): formation, Chemistry, classification, receptors, and Diseases related to AGEs. Cells 11. https://doi.org/10.3390/cells11081312
Bongarzone S, Savickas V, Luzi F, Gee AD (2017) Targeting the receptor for Advanced Glycation End-products (RAGE): a Medicinal Chemistry Perspective. J Med Chem 60:7213–7232. https://doi.org/10.1021/acs.jmedchem.7b00058
doi: 10.1021/acs.jmedchem.7b00058
pubmed: 28482155
pmcid: 5601361
Masjedi F, Keshtgar S, Zal F, Talaei-Khozani T, Sameti S, Fallahi S, Kazeroni M (2020) Effects of vitamin D on steroidogenesis, reactive oxygen species production, and enzymatic anti-oxidant defense in human granulosa cells of normal and polycystic ovaries. J Steroid Biochem Mol Biol 197:105521. https://doi.org/10.1016/j.jsbmb.2019.105521
doi: 10.1016/j.jsbmb.2019.105521
pubmed: 31705961
Mehdinejadiani S, Amidi F, Mehdizadeh M, Barati M, Safdarian L, Aflatoonian R, Alyasin A, Aghahosseini M, Pazhohan A, Hayat P, Mohammadzadeh Kazorgah F, Sobhani A (2018) The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with polycystic ovarian syndrome. Gynecol Endocrinol 34:775–780. https://doi.org/10.1080/09513590.2018.1446934
doi: 10.1080/09513590.2018.1446934
pubmed: 29510649
Merhi Z, Kandaraki EA, Diamanti-Kandarakis E (2019) Implications and future perspectives of AGEs in PCOS Pathophysiology. Trends Endocrinol Metab 30:150–162. https://doi.org/10.1016/j.tem.2019.01.005
doi: 10.1016/j.tem.2019.01.005
pubmed: 30712978
Stensen MH, Tanbo T, Storeng R, Fedorcsak P (2014) Advanced glycation end products and their receptor contribute to ovarian ageing. Hum Reprod 29:125–134. https://doi.org/10.1093/humrep/det419
doi: 10.1093/humrep/det419
pubmed: 24256989
Garg D, Merhi Z (2016) Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS. Reprod Biol Endocrinol 14:71. https://doi.org/10.1186/s12958-016-0205-6
doi: 10.1186/s12958-016-0205-6
pubmed: 27769286
pmcid: 5073880
Diamanti-Kandarakis E, Chatzigeorgiou A, Papageorgiou E, Koundouras D, Koutsilieris M (2016) Advanced glycation end-products and insulin signaling in granulosa cells. Exp Biol Med 241:1438–1445
doi: 10.1177/1535370215584937
Merhi Z, Buyuk E, Cipolla M (2018) Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D. Mol Hum Reprod 24:318–326
doi: 10.1093/molehr/gay014
pubmed: 29538679
pmcid: 6530817
Takahashi N, Harada M, Azhary JM, Kunitomi C, Nose E, Terao H, Koike H, Wada-Hiraike O, Hirata T, Hirota Y (2019) Accumulation of advanced glycation end products in follicles is associated with poor oocyte developmental competence. Mol Hum Reprod 25:684–694
doi: 10.1093/molehr/gaz050
pubmed: 31504800
Chen JL, Francis J (2012) Pyridoxamine, advanced glycation inhibition, and diabetic nephropathy. J Am Soc Nephrol 23:6–8. https://doi.org/10.1681/asn.2011111097
doi: 10.1681/asn.2011111097
pubmed: 22158434
Ramis R, Ortega-Castro J, Caballero C, Casasnovas R, Cerrillo A, Vilanova B, Adrover M, Frau J (2019) How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Anti-oxidant Activity. Anti-oxidants (Basel) 8. https://doi.org/10.3390/antiox8090344
Lyon P, Strippoli V, Fang B, Cimmino L (2020) B vitamins and One-Carbon Metabolism: implications in Human Health and Disease. Nutrients 12. https://doi.org/10.3390/nu12092867
Glaeser JD, Ju D, Tawackoli W, Yang JH, Salehi K, Stefanovic T, Kanim LEA, Avalos P, Kaneda G, Stephan S, Metzger MF, Bae HW, Sheyn D (2020) Advanced glycation end product inhibitor pyridoxamine attenuates IVD degeneration in type 2 Diabetic rats. Int J Mol Sci 21. https://doi.org/10.3390/ijms21249709
Aboelenain M, Balboula AZ, Kawahara M, El-Monem Montaser A, Zaabel SM, Kim SW, Nagano M, Takahashi M (2017) Pyridoxine supplementation during oocyte maturation improves the development and quality of bovine preimplantation embryos. Theriogenology 91:127–133. https://doi.org/10.1016/j.theriogenology.2016.12.022
doi: 10.1016/j.theriogenology.2016.12.022
pubmed: 28215677
Chen X, Lu T, Wang X, Sun X, Zhang J, Zhou K, Ji X, Sun R, Wang X, Chen M, Ling X (2020) Metabolic alterations associated with polycystic ovary syndrome: a UPLC Q-Exactive based metabolomic study. Clin Chim Acta 502:280–286. https://doi.org/10.1016/j.cca.2019.11.016
doi: 10.1016/j.cca.2019.11.016
pubmed: 31758934
Kilicdag EB, Bagis T, Tarim E, Aslan E, Erkanli S, Simsek E, Haydardedeoglu B, Kuscu E (2005) Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial. Hum Reprod 20:1521–1528. https://doi.org/10.1093/humrep/deh825
doi: 10.1093/humrep/deh825
pubmed: 15790610
Hestiantoro A, Astuti BPK, Joyo EO, Febri RR, Silvana V, Muharam R (2022) Vitamin B(3) (niacin), B(6), C, and iron intake are associated with the free androgen index, especially in normoandrogenic polycystic ovary syndrome. J Turk Ger Gynecol Assoc 23:130–136. https://doi.org/10.4274/jtgga.galenos.2022.2022-2-1
doi: 10.4274/jtgga.galenos.2022.2022-2-1
pubmed: 35781735
Chen X, Thibeault S (2013) Effect of DMSO concentration, cell density and needle gauge on the viability of cryopreserved cells in three dimensional hyaluronan hydrogel. Annu Int Conf IEEE Eng Med Biol Soc 2013:6228–6231. https://doi.org/10.1109/embc.2013.6610976
doi: 10.1109/embc.2013.6610976
pubmed: 24111163
Tatone C, Di Emidio G, Placidi M, Rossi G, Ruggieri S, Taccaliti C, D’Alfonso A, Amicarelli F, Guido M (2021) AGEs-related dysfunctions in PCOS: evidence from animal and clinical research. J Endocrinol 251:R1–r9. https://doi.org/10.1530/joe-21-0143
doi: 10.1530/joe-21-0143
pubmed: 34448729
Mouanness M, Merhi Z (2022) Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways. Nutrients [serial on the Internet]. ; 14(5)
Garg D, Merhi Z (2015) Advanced glycation end products: link between diet and ovulatory dysfunction in PCOS? Nutrients 7:10129–10144
doi: 10.3390/nu7125524
pubmed: 26690206
pmcid: 4690076
Pertynska-Marczewska M, Diamanti-Kandarakis E (2017) Aging ovary and the role for advanced glycation end products. Menopause 24:345–351
doi: 10.1097/GME.0000000000000755
pubmed: 27749734
Wang X, Wang L, Xiang W (2023) Mechanisms of ovarian aging in women: a review. J Ovarian Res 16:67. https://doi.org/10.1186/s13048-023-01151-z
doi: 10.1186/s13048-023-01151-z
pubmed: 37024976
pmcid: 10080932
Merhi Z, Irani M, Doswell AD, Ambroggio J (2014) Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve. J Clin Endocrinol Metab 99:E226–E233
doi: 10.1210/jc.2013-3839
pubmed: 24276462
Zhu J-l, Cai Y-q, Long S-l, Chen Z, Mo Z-c (2020) The role of advanced glycation end products in human infertility. Life Sci 255:117830. https://doi.org/10.1016/j.lfs.2020.117830
doi: 10.1016/j.lfs.2020.117830
pubmed: 32450172
Ravichandran G, Lakshmanan DK, Raju K, Elangovan A, Nambirajan G, Devanesan AA, Thilagar S (2019) Food advanced glycation end products as potential endocrine disruptors: an emerging threat to contemporary and future generation. Environ Int 123:486–500. https://doi.org/10.1016/j.envint.2018.12.032
doi: 10.1016/j.envint.2018.12.032
pubmed: 30622074
Niu G, Guo J, Tian Y, Zhao K, Li J, Xiao Q (2018) α–lipoic acid can greatly alleviate the toxic effect of AGES on SH–SY5Y cells. Int J Mol Med 41:2855–2864
pubmed: 29436603
Prantner D, Nallar S, Vogel SN (2020) The role of RAGE in host pathology and crosstalk between RAGE and TLR4 in innate immune signal transduction pathways. FASEB J 34:15659–15674. https://doi.org/10.1096/fj.202002136R
doi: 10.1096/fj.202002136R
pubmed: 33131091
Merhi Z, Du XQ, Charron MJ (2020) Perinatal exposure to high dietary advanced glycation end products affects the reproductive system in female offspring in mice. Mol Hum Reprod 26:615–623
doi: 10.1093/molehr/gaaa046
pubmed: 32609365
Huang B, Ren X, Wu L, Zhu L, Xu B, Li Y, Ai J, Jin L (2016) Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles. PLoS ONE 11:e0145895
doi: 10.1371/journal.pone.0145895
pubmed: 26745711
pmcid: 4706317
Kandaraki EA, Chatzigeorgiou A, Papageorgiou E, Piperi C, Adamopoulos C, Papavassiliou AG, Koutsilieris M, Diamanti-Kandarakis E (2018) Advanced glycation end products interfere in luteinizing hormone and follicle stimulating hormone signaling in human granulosa KGN cells. Exp Biol Med (Maywood) 243:29–33. https://doi.org/10.1177/1535370217731288
doi: 10.1177/1535370217731288
pubmed: 28914097
Dompe C, Kulus M, Stefańska K, Kranc W, Chermuła B, Bryl R, Pieńkowski W, Nawrocki MJ, Petitte JN, Stelmach B, Mozdziak P, Jeseta M, Pawelczyk L, Jaśkowski JM, Piotrowska-Kempisty H, Spaczyński RZ, Nowicki M, Kempisty B (2021) Human granulosa Cells-Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis. https://doi.org/10.3390/cells10061396 . Cells 10
Gao EM, Turathum B, Wang L, Zhang D, Liu YB, Tang RX, Chian RC (2022) The Differential Metabolomes in Cumulus and Mural Granulosa cells from human pre-ovulatory follicles. Reprod Sci 29:1343–1356. https://doi.org/10.1007/s43032-021-00691-3
doi: 10.1007/s43032-021-00691-3
pubmed: 34374964
Turgut F, Bolton WK (2010) Potential New Therapeutic Agents for Diabetic kidney disease. Am J Kidney Dis 55:928–940. https://doi.org/10.1053/j.ajkd.2009.11.021
doi: 10.1053/j.ajkd.2009.11.021
pubmed: 20138415
Steegers-Theunissen RP, Steegers EA, Thomas CM, Hollanders HM, Peereboom-Stegeman JH, Trijbels FJ, Eskes TK (1993) Study on the presence of homocysteine in ovarian follicular fluid. Fertil Steril 60:1006–1010. https://doi.org/10.1016/s0015-0282(16)56401-2
doi: 10.1016/s0015-0282(16)56401-2
pubmed: 8243678
Allgood VE, Cidlowski JA (1992) Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily. J Biol Chem 267:3819–3824
doi: 10.1016/S0021-9258(19)50599-3
pubmed: 1310983
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC (2008) Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility. Fertil Steril 89:668–676. https://doi.org/10.1016/j.fertnstert.2007.03.089
doi: 10.1016/j.fertnstert.2007.03.089
pubmed: 17624345
Govahi A, Amjadi F, Nasr-Esfahani MH, Raoufi E, Mehdizadeh M (2022) Accompaniment of Time-Lapse Parameters and Cumulus Cell RNA-Sequencing in embryo evaluation. Reprod Sci 29:395–409. https://doi.org/10.1007/s43032-021-00748-3
doi: 10.1007/s43032-021-00748-3
pubmed: 34642913
Zhao Y, Hu S, Zhai W, Wang M, Ran L (2022) Clinical study of Progesterone combined with vitamin B6 in the treatment of Amenorrhea Endocrine Disorders caused by antipsychotics. Comput Math Methods Med 2022:2436322. https://doi.org/10.1155/2022/2436322
doi: 10.1155/2022/2436322
pubmed: 36072776
pmcid: 9441377
Szczuko M, Hawryłkowicz V, Kikut J, Drozd A (2020) The implications of vitamin content in the plasma in reference to the parameters of carbohydrate metabolism and hormone and lipid profiles in PCOS. J Steroid Biochem Mol Biol 198:105570. https://doi.org/10.1016/j.jsbmb.2019.105570
doi: 10.1016/j.jsbmb.2019.105570
pubmed: 31883924
Scammahorn JJ, Nguyen ITN, Bos EM, Van Goor H, Joles JA (2021) Fighting Oxidative Stress with Sulfur: Hydrogen Sulfide in the Renal and Cardiovascular Systems. Anti-oxidants (Basel) 10. https://doi.org/10.3390/antiox10030373
Yang J, Minkler P, Grove D, Wang R, Willard B, Dweik R, Hine C (2019) Non-enzymatic hydrogen sulfide production from cysteine in blood is catalyzed by iron and vitamin B6. Commun Biol 2:194. https://doi.org/10.1038/s42003-019-0431-5
doi: 10.1038/s42003-019-0431-5
pubmed: 31123718
pmcid: 6529520
Golestanfar A, Niasari-Naslaji A, Jafarpour F, Rouhollahi S, Rezaei N, Menezo Y, Dattilo M, Nasr-Esfahani MH (2022) Metabolic enhancement of the one carbon metabolism (OCM) in bovine oocytes IVM increases the blastocyst rate: evidences for a OCM checkpoint. Sci Rep 12:20629. https://doi.org/10.1038/s41598-022-25083-8
doi: 10.1038/s41598-022-25083-8
pubmed: 36450805
pmcid: 9712338
Ueland PM, Ulvik A, Rios-Avila L, Midttun Ø, Gregory JF (2015) Direct and functional biomarkers of vitamin B6 status. Annu Rev Nutr 35:33–70. https://doi.org/10.1146/annurev-nutr-071714-034330
doi: 10.1146/annurev-nutr-071714-034330
pubmed: 25974692
pmcid: 5988249
Furness D, Fenech M, Dekker G, Khong TY, Roberts C, Hague W (2013) Folate, vitamin B12, vitamin B6 and homocysteine: impact on pregnancy outcome. Matern Child Nutr 9:155–166. https://doi.org/10.1111/j.1740-8709.2011.00364.x
doi: 10.1111/j.1740-8709.2011.00364.x
pubmed: 22023381
Deepa R, Mandal S, Van Schayck OCP, Babu GR (2023) Vitamin B6 levels and impaired Folate Status but not vitamin B12 Associated with Low Birth Weight: results from the MAASTHI Birth Cohort in South India. Nutrients 15. https://doi.org/10.3390/nu15071793
Ronnenberg AG, Goldman MB, Chen D, Aitken IW, Willett WC, Selhub J, Xu X (2002) Preconception homocysteine and B vitamin status and birth outcomes in chinese women. Am J Clin Nutr 76:1385–1391. https://doi.org/10.1093/ajcn/76.6.1385
doi: 10.1093/ajcn/76.6.1385
pubmed: 12450907
Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, Huang A, Wang X (2007) Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol 166:304–312. https://doi.org/10.1093/aje/kwm078
doi: 10.1093/aje/kwm078
pubmed: 17478435
Goddijn-Wessel TA, Wouters MG, van de Molen EF, Spuijbroek MD, Steegers-Theunissen RP, Blom HJ, Boers GH, Eskes TK (1996) Hyperhomocysteinemia: a risk factor for placental abruption or infarction. Eur J Obstet Gynecol Reprod Biol 66:23–29. https://doi.org/10.1016/0301-2115(96)02383-4
doi: 10.1016/0301-2115(96)02383-4
pubmed: 8735754
Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Borm GF, Steegers-Theunissen RP, Eskes TK (1993) Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 60:820–825
doi: 10.1016/S0015-0282(16)56282-7
pubmed: 8224267
Bjørke-Monsen AL, Varsi K, Sakkestad ST, Ulvik A, Ueland PM (2023) Assessment of vitamin B6 status in never-pregnant, pregnant and postpartum women and their infants. Eur J Nutr 62:867–878. https://doi.org/10.1007/s00394-022-03033-4
doi: 10.1007/s00394-022-03033-4
pubmed: 36318283