{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:31:27Z","timestamp":1780918287043,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia","award":["CN-2-072\/N\/1\/Z"],"award-info":[{"award-number":["CN-2-072\/N\/1\/Z"]}]},{"name":"Academy of Silesia in Katowice","award":["CN-2-072\/N\/1\/Z"],"award-info":[{"award-number":["CN-2-072\/N\/1\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic\u2013pituitary\u2013gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol\/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol\/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol\/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.<\/jats:p>","DOI":"10.3390\/nu16142362","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T12:20:38Z","timestamp":1721650838000},"page":"2362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-4563","authenticated-orcid":false,"given":"Karolina","family":"Kowalcze","sequence":"first","affiliation":[{"name":"Department of Patophysiology, Faculty of Medicine, Academy of Silesia, Rolna 43, 40-555 Katowice, Poland"},{"name":"Department of Pediatrics in Bytom, Faculty of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-2620","authenticated-orcid":false,"given":"Robert","family":"Krysiak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-4269","authenticated-orcid":false,"given":"Giuseppe","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-5262","authenticated-orcid":false,"given":"Johannes","family":"Ott","sequence":"additional","affiliation":[{"name":"Clinical Division of Gynecologic Endocrinology and Reproductive Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lanciotti, L., Cofini, M., Leonardi, A., Penta, L., and Esposito, S. (2018). Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00410"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000508329","article-title":"Minipuberty: Why does it happen?","volume":"93","author":"Becker","year":"2020","journal-title":"Horm. Res. Paediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000362414","article-title":"Activation of the hypothalamic-pituitary-gonadal axis in infancy: Minipuberty","volume":"82","author":"Sankilampi","year":"2014","journal-title":"Horm. Res. Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bizzarri, C., and Cappa, M. (2020). Ontogeny of hypothalamus-pituitary gonadal axis and minipuberty: An ongoing debate?. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00187"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lucaccioni, L., Trevisani, V., Boncompagni, A., Marrozzini, L., Berardi, A., and Iughetti, L. (2021). Minipuberty: Looking back to understand moving forward. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.612235"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1210\/clinem\/dgac363","article-title":"A biphasic pattern of reproductive hormones in healthy female infants: The Copenhagen minipuberty study","volume":"107","author":"Ljubicic","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chachlaki, K., Le Duc, K., Storme, L., and Prevot, V. (2024). Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics. J. Neuroendocrinol., e13387.","DOI":"10.1111\/jne.13387"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1515\/jpem-2019-0388","article-title":"The association between vitamin D levels and precocious puberty: A meta-analysis","volume":"33","author":"Liu","year":"2020","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cheng, H., Chen, D., and Gao, H. (2023). An updated meta-analysis of the relationship between vitamin D levels and precocious puberty. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1298374"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1039\/D3FO00665D","article-title":"Does vitamin D have a potential role in precocious puberty? A meta-analysis","volume":"14","author":"Wu","year":"2023","journal-title":"Food Funct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100244","DOI":"10.1016\/j.clinsp.2023.100244","article-title":"Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls","volume":"78","author":"Gan","year":"2023","journal-title":"Clinics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1515\/jpem-2023-0381","article-title":"Correlation between serum vitamin D level and uterine volume in girls with idiopathic central precocious puberty","volume":"37","author":"Sun","year":"2023","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.3945\/ajcn.111.018168","article-title":"Vitamin D deficiency and age at menarche: A prospective study","volume":"94","author":"Villamor","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/ped.13682","article-title":"Vitamin D status and premature adrenarche","volume":"60","author":"Bideci","year":"2018","journal-title":"Pediatr. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xu, L., Li, P., and Yuan, D. (2023). Confirming the association between low serum 25OHD levels in girls with central precocious puberty and its severity. BMC Pediatr., 23.","DOI":"10.1186\/s12887-023-04447-7"},{"key":"ref_16","first-page":"725","article-title":"Vitamin D receptor gene polymorphisms and sex steroid secretion in girls with precocious pubarche in Southern Brazil: A pilot study","volume":"35","author":"Santos","year":"2012","journal-title":"J. Endocrinol. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/ije\/dyad060","article-title":"The estimated effect of season and vitamin D in the first trimester on pubertal timing in girls and boys: A cohort study and an instrumental variable analysis","volume":"52","author":"Brix","year":"2023","journal-title":"Int. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1159\/000517640","article-title":"Sun exposure and vitamin D","volume":"55","author":"Knuschke","year":"2021","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kowalcze, K., Krysiak, R., and Obuchowicz, A. (2023). Minipuberty in sons of women with low vitamin D status during pregnancy. Nutrients, 15.","DOI":"10.3390\/nu15224729"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Krysiak, R., Kowalcze, K., and Okopie\u0144, B. (2023). Cardiometabolic effects of cabergoline and combined oral contraceptive pills in young women with hyperprolactinemia: A pilot study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12093208"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kowalcze, K., Krysiak, R., and Obuchowicz, A. (2023). The impact of maternal hypothyroidism during pregnancy on minipuberty in boys. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247649"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13006-023-00564-2","article-title":"Calcium, zinc, and vitamin D in breast milk: A systematic review and meta-analysis","volume":"18","author":"Yao","year":"2023","journal-title":"Int. Breastfeed. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1210\/jc.2016-1672","article-title":"Genetic variations in FSH action affect sex hormone levels and breast tissue size in infant girls: A pilot study","volume":"101","author":"Henriksen","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1289\/ehp.1509693","article-title":"Environmental chemicals in urine and blood: Improving methods for creatinine and lipid adjustment","volume":"124","author":"Upson","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Krysiak, R., Basiak, M., Machnik, G., Szkr\u00f3bka, W., and Okopie\u0144, B. (2023). Vitamin D status determines cardiometabolic effects of cabergoline in women with elevated prolactin levels: A pilot study. Nutrients, 15.","DOI":"10.3390\/nu15102303"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1210\/jc.2013-1677","article-title":"Postnatal ovarian activation has effects in estrogen target tissues in infant girls","volume":"98","author":"Turpeinen","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/ppe.12673","article-title":"Characterization of ovarian development in girls from born to 9 months","volume":"35","author":"Chin","year":"2021","journal-title":"Paediatr. Paediatr. Perinat. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1210\/jc.2011-1502","article-title":"Postnatal developmental changes in the pituitary-ovarian axis in preterm and term infant girls","volume":"96","author":"Kallio","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/cen.13716","article-title":"Sexual dimorphism in postnatal gonadotrophin levels in infancy reflects diverse maturation of the ovarian and testicular hormone synthesis","volume":"89","author":"Dunkel","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4274\/jcrpe.galenos.2024.2023-11-2","article-title":"Salivary sex steroid levels in infants and the relation with infantile colic","volume":"16","author":"Tan","year":"2024","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1210\/jcem-65-5-862","article-title":"Estrone and estradiol concentrations in human ovaries, testes, and adrenals during the first two years of life","volume":"65","author":"Bidlingmaier","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","first-page":"145","article-title":"The aromatase cytochrome P-450 and its clinical impact","volume":"57","author":"Meinhardt","year":"2002","journal-title":"Horm. Res."},{"key":"ref_34","first-page":"934","article-title":"1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokines in human macrophages","volume":"30","author":"Villaggio","year":"2012","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jsbmb.2010.02.009","article-title":"Vitamin D and breast cancer: Inhibition of estrogen synthesis and signaling","volume":"121","author":"Krishnan","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"154460","DOI":"10.1016\/j.metabol.2020.154460","article-title":"AMP-activated protein kinase (AMPK) signaling in GnRH neurons links energy status and reproduction","volume":"115","author":"Franssen","year":"2021","journal-title":"Metabolism"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R51","DOI":"10.1530\/JOE-19-0223","article-title":"Novel mechanisms for the metabolic control of puberty: Implications for pubertal alterations in early-onset obesity and malnutrition","volume":"242","author":"Vazquez","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Krysiak, R., Kowalcze, K., Szkr\u00f3bka, W., and Okopie\u0144, B. (2023). Vitamin D status determines the impact of metformin on gonadotropin levels in postmenopausal women. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113715"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1515\/jpem-2022-0491","article-title":"Molecular mechanisms involved in fetal programming and disease origin in adulthood","volume":"36","author":"Escobedo","year":"2023","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Burlo, F., Lorenzon, B., Tamaro, G., Fabretto, A., Buonomo, F., Peinkhofer, M., Vidonis, V., Vittori, G., Faleschini, E., and Barbi, E. (2023). Prevalence and characteristics of thelarche variant. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1303989"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"84","DOI":"10.6065\/apem.2040094.047","article-title":"Minipuberty of human infancy\u2014A window of opportunity to evaluate hypogonadism and differences of sex development?","volume":"25","author":"Renaul","year":"2020","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ljubicic, M.L., Madsen, A., Upners, E.N., Fischer, M.B., Busch, A.S., Frederiksen, H., Johannsen, T.H., Juul, A., and Hagen, C.P. (2022). Longitudinal evaluation of breast tissue in healthy infants: Prevalence and relation to reproductive hormones and growth factors. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1048660"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/cen.13856","article-title":"Evaluation of vitamin D status and its correlation with gonadal function in children at mini-puberty","volume":"90","author":"Atay","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0140-6736(22)01330-7","article-title":"Congenital adrenal hyperplasia","volume":"401","author":"Auer","year":"2023","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1079\/BJN19870005","article-title":"Studies on the measurement of 25-hydroxy vitamin D in human saliva","volume":"57","author":"Fairney","year":"1987","journal-title":"Br. J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/bs.acc.2016.07.002","article-title":"Vitamin D testing-where are we and what is on the horizon?","volume":"78","author":"Heureux","year":"2017","journal-title":"Adv. Clin. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jsbmb.2017.09.003","article-title":"The art of measuring steroids: Principles and practice of current hormonal steroid analysis","volume":"179","author":"Wudy","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1177\/070674370104600111","article-title":"Regression toward the mean: Its etiology, diagnosis, and treatment","volume":"46","author":"Streiner","year":"2001","journal-title":"Can. J. Psychiatry"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:34Z","timestamp":1760109634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,21]]},"references-count":48,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["nu16142362"],"URL":"https:\/\/doi.org\/10.3390\/nu16142362","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,21]]}}}