Vitamin D Effects on Folliculogenesis via Ovarian Paracrine Factors

Year 2022, Volume: 3 Issue: 3, 316 - 321, 30.11.2022

Damla Gül Fındık

https://doi.org/10.48176/esmj.2022.93

Abstract

The folliculogenesis mechanism is a complex process involving various hormones, growth factors and signaling molecules. Future research on the mechanisms of follicular development will provide more comprehensive data on female reproductive life. Vitamin D affects folliculogenesis through steroidogenesis. Vitamin D receptor signaling in granulosa cells regulates hormone secretions through steroidogenic enzymes. Vitamin D and folliculogenesis associated mechanism is still not elucidated. Various ovarian-derived autocrineparacrine factors involved in different stages of folliculogenesis have been shown in studies. Vitamin D effects on folliculogenesis via these factors are significant to understanding the underlying mechanism. Inhibitors of dormant primordial follicle activation are Forkhead box O3a, anti-müllerian hormone, Phosphatase and tensin homolog and p27. Among these factors, Forkhead box O3a is an important molecule for primordial follicle activity regulation and apoptosis mechanisms in the ovary. The factors involved in the development of preantral follicle from the primary follicle are Transforming Growth Factor-β, Growth and differentiation factor 9, Bone morphogenetic protein 4,7,15 and activin. Growth and differentiation factor 9 and Bone morphogenetic protein 15 induce granulosa cell proliferation and preantral follicle development. This review aims to describe the association between Vitamin D and folliculogenesis through steroidogenesis and ovarian paracrine factors.

Keywords

AMH, BMP15, FOXO, GDF9, steroidogenesis

Vitamin D’nin Ovaryan Parakrin Faktörler ile Follikülogenez Üzerindeki Etkisi

Abstract

Follikülogenez mekanizması çeşitli hormonları, büyüme faktörlerini ve sinyal moleküllerini içeren karmaşık bir süreçtir. Foliküler gelişim mekanizmaları üzerine gelecekteki araştırmalar, dişi reprodüktif yaşamı hakkında daha kapsamlı veriler sağlayacaktır. Vitamin D, steroidogenez yoluyla follikülogenezi etkiler. Granüloza hücrelerinde Vitamin D reseptör sinyali hormon salgılarını steroidojenik enzimler aracılığıyla düzenler. Vitamin D ve follikülogenez ile ilişkili mekanizma hala aydınlatılamamıştır. Follikülogenezin farklı evrelerinde yer alan çeşitli over kaynaklı otokrin-parakrin faktörler çalışmalarda gösterilmiştir. Bu faktörler yoluyla follikülogenez üzerindeki Vitamin D etkileri, altta yatan mekanizmayı anlamak için önemlidir. Sessiz primordial follikül aktivasyonunun inhibitörleri, Forkhead box O3a, anti-müllerian hormon, Fosfataz ve tensin homologu ve p27’dir. Bu faktörler arasından Forkhead box O3a, overde primordial folikül aktivite regülasyonu ve apoptoz mekanizmaları için önemli bir moleküldür. Primer follikülden preantral follikülün gelişiminde rol oynayan faktörler, dönüştürücü büyüme faktörü-β, büyüme ve farklılaşma faktörü 9, kemik morfogenetik protein 4,7,15 ve aktivindir. Bu derleme, steroidogenez ve ovaryan parakrin faktörler aracılığıyla VitD ve follikülogenez arasındaki ilişkiyi açıklamayı amaçlamaktadır.

Keywords

AMH, BMP15, FOXO, GDF9, steroidogenez

References

• 1. Grzesiak M. Vitamin D3 action within the ovary - an updated review. Physiological research. 2020;69:371-8.
• 2. Xu F, Wolf S, Green Or, Xu J. Vitamin D in follicular development and oocyte maturation. Reproduction (Cambridge, England). 2021;161:R129-R37.
• 3. Xu J, Lawson MS, Xu F et al. Vitamin D3 Regulates Follicular Development and Intrafollicular Vitamin D Biosynthesis and Signaling in the Primate Ovary. Frontiers in physiology. 2018;9:1600-.
• 4. Keane KN, Cruzat VF, Calton EK et al. Molecular actions of vitamin D in reproductive cell biology. Reproduction. 2017;153:R29-r42.
• 5. Bakhshalizadeh S, Amidi F, Alleyassin A, Soleimani M, Shirazi R, Shabani Nashtaei M. Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome. Syst Biol Reprod Med. 2017;63:150-61.
• 6. Shahrokhi SZ, Ghaffari F, Kazerouni F. Role of vitamin D in female reproduction. Clinica chimica acta. 2016;455:33-8.
• 7. Masjedi F, Keshtgar S, Zal F et al. Effects of vitamin D on steroidogenesis, reactive oxygen species production, and enzymatic antioxidant defense in human granulosa cells of normal and polycystic ovaries. J Steroid Biochem Mol Biol. 2020;197:105521.
• 8. Merhi Z, Doswell A, Krebs K, Cipolla M. Vitamin D Alters Genes Involved in Follicular Development and Steroidogenesis in Human Cumulus Granulosa Cells. The Journal of Clinical Endocrinology & Metabolism. 2014;99:E1137-E45.
• 9. Yao X, Zhang G, Guo Y et al. Vitamin D receptor expression and potential role of vitamin D on cell proliferation and steroidogenesis in goat ovarian granulosa cells. Theriogenology. 2017;102:162-73.
• 10. Berry S, Seidler K, Neil J. Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome. Journal of Reproductive Immunology. 2022;151:103633.
• 11. Dicken CL, Israel DD, Davis JB et al. Peripubertal vitamin D(3) deficiency delays puberty and disrupts the estrous cycle in adult female mice. Biol Reprod. 2012;87:51.
• 12. Behmanesh N, Abedelahi A, Charoudeh HN, Alihemmati A. Effects of vitamin D supplementation on follicular development, gonadotropins and sex hormone concentrations, and insulin resistance in induced polycystic ovary syndrome. Turkish journal of obstetrics and gynecology. 2019;16:143.
• 13. Oktem O, Urman B. Understanding follicle growth in vivo. Human reproduction. 2010;25:2944-54.
• 14. Rimon-Dahari N, Yerushalmi-Heinemann L, Alyagor L, Dekel N: Ovarian folliculogenesis. In: Molecular mechanisms of cell differentiation in gonad development. edn.: Springer; 2016: 167-90.
• 15. Belli M, Shimasaki S. Molecular Aspects and Clinical Relevance of GDF9 and BMP15 in Ovarian Function. Vitamins and hormones. 2018;107:317-48.
• 16. Liu M-n, Zhang K, Xu T-m. The role of BMP15 and GDF9 in the pathogenesis of primary ovarian insufficiency. Human Fertility. 2021;24:325-32.
• 17. Sanfins A, Rodrigues P, Albertini DF. GDF-9 and BMP-15 direct the follicle symphony. Journal of Assisted Reproduction and Genetics. 2018;35:1741-50.
• 18. Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol. 2010;45:257-79.
• 19. Chang H-M, Qiao J, Leung PCK. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Human reproduction update. 2016;23:1-18.
• 20. El-Derany MO, Said RS, El-Demerdash E. Bone marrow-derived mesenchymal stem cells reverse radiotherapy-induced premature ovarian failure: emphasis on signal integration of TGF-β, Wnt/β-catenin and Hippo pathways. Stem Cell Reviews and Reports. 2021;17:1429-45.
• 21. Paulini F, Melo EO. Effects of Growth and Differentiation Factor 9 and Bone Morphogenetic Protein 15 overexpression on the steroidogenic metabolism in bovine granulosa cells in vitro. Reprod Domest Anim. 2021;56:837-47.
• 22. Delgado JC, Hamilton T, Mendes CM et al. Bone morphogenetic protein 15 supplementation enhances cumulus expansion, nuclear maturation and progesterone production of in vitro-matured bovine cumulus-oocyte complexes. Reprod Domest Anim. 2021;56:754-63.
• 23. Gupta SD, Dhar B, Kundu S et al. Association between gene expression levels of GDF9 and BMP15 and clinicopathological factors in the prognosis of female infertility in northeast Indian populations. Meta Gene. 2021;30:100964.
• 24. Nikmard F, Hosseini E, Bakhtiyari M, Ashrafi M, Amidi F, Aflatoonian R. The boosting effects of melatonin on the expression of related genes to oocyte maturation and antioxidant pathways: a polycystic ovary syndrome-mouse model. Journal of Ovarian Research. 2022;15:1-11.
• 25. Daneshjou D, Mehranjani MS, Zadehmodarres S, Shariatzadeh SMA, Mofarahe ZS. Sitagliptin/metformin improves the fertilization rate and embryo quality in polycystic ovary syndrome patients through increasing the expression of GDF9 and BMP15: A new alternative to metformin (a randomized trial). J Reprod Immunol. 2022;150:103499.
• 26. Gao H, Li Y, Yan W, Gao F. The effect of vitamin D supplementation on blood lipids in patients with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. International journal of endocrinology. 2021;2021.
• 27. Zhao J-F, Li B-X, Zhang Q. Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study. Ann Palliat Med. 2021;10:169-83.
• 28. Paffoni A, Somigliana E, Sarais V et al. Effect of vitamin D supplementation on assisted reproduction technology (ART) outcomes and underlying biological mechanisms: protocol of a randomized clinical controlled trial. The “supplementation of vitamin D and reproductive outcome” (SUNDRO) study. BMC Pregnancy and Childbirth. 2019;19:395.
• 29. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978-86.
• 30. Sui X-X, Luo L-L, Xu J-J, Fu Y-C. Evidence that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary. Biochemistry and cell biology. 2010;88:621-8.
• 31. Zhang M, Zhang X. The role of PI3K/AKT/FOXO signaling in psoriasis. Arch Dermatol Res. 2019;311:83-91.
• 32. Chen H, Fu Y, Guo Z, Zhou X. MicroRNA-29c-3p participates in insulin function to modulate polycystic ovary syndrome via targeting Forkhead box O 3. Bioengineered. 2022;13:4361-71.
• 33. Wang F, Chen X, Sun B et al. Hypermethylation-mediated downregulation of lncRNA PVT1 promotes granulosa cell apoptosis in premature ovarian insufficiency via interacting with Foxo3a. J Cell Physiol. 2021;236:5162-75.
• 34. Li L, Shi X, Shi Y, Wang Z. The signaling pathways involved in ovarian follicle development. Frontiers in Physiology. 2021;12:730196.
• 35. Zeng J, Sun Y, Li X et al. 2,5-Hexanedione influences primordial follicular development in cultured neonatal mouse ovaries by interfering with the PI3K signaling pathway via miR-214-3p. Toxicol Appl Pharmacol. 2020;409:115335.
• 36. Zheng S, Ma M, Chen Y, Li M. Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure. Basic & Clinical Pharmacology & Toxicology. 2022;130:240-53.
• 37. Barberino RS, Lins T, Monte APO et al. Melatonin Attenuates Cyclophosphamide-Induced Primordial Follicle Loss by Interaction with MT(1) Receptor and Modulation of PTEN/Akt/FOXO3a Proteins in the Mouse Ovary. Reprod Sci. 2021.
• 38. Kim J, You Y-J. Oocyte quiescence: From formation to awakening. Endocrinology. 2022;163:bqac049.
• 39. Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Molecular reproduction and development. 2011;78:9-21.
• 40. Tan M, Cheng Y, Zhong X et al. LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway. Aging (Albany NY). 2021;13:4617-33.
• 41. Yildizgören MT, Togral AK. Preliminary evidence for vitamin D deficiency in nodulocystic acne. Dermato-endocrinology. 2014;6:e983687.
• 42. An B-S, Tavera-Mendoza LE, Dimitrov V et al. Stimulation of Sirt1-Regulated FoxO Protein Function by the Ligand-Bound Vitamin D Receptor. Molecular and Cellular Biology. 2010;30:4890-900.
• 43. Shariev A, Painter N, Reeve VE et al. PTEN: A novel target for vitamin D in melanoma. J Steroid Biochem Mol Biol. 2022;218:106059.
• 44. Gouveia BB, Barberino RS, Dos Santos Silva RL et al. Involvement of PTEN and FOXO3a Proteins in the Protective Activity of Protocatechuic Acid Against Cisplatin-Induced Ovarian Toxicity in Mice. Reprod Sci. 2021;28:865-76.
• 45. Monte APO, Bezerra MÉS, Menezes VG et al. Involvement of Phosphorylated Akt and FOXO3a in the Effects of Growth and Differentiation Factor-9 (GDF-9) on Inhibition of Follicular Apoptosis and Induction of Granulosa Cell Proliferation After In Vitro Culture of Sheep Ovarian Tissue. Reproductive Sciences. 2021;28:2174-85.
• 46. Qin C, Xia X, Fan Y et al. A novel, noncoding-RNA-mediated, post-transcriptional mechanism of anti-Mullerian hormone regulation by the H19/let-7 axis. Biology of reproduction. 2019;100:101-11.
• 47. Patton BK, Madadi S, Pangas SA. Control of ovarian follicle development by TGF-β family signaling. Current Opinion in Endocrine and Metabolic Research. 2021;18:102-10.
• 48. Kumariya S, Ubba V, Jha RK, Gayen JR. Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective. Autophagy. 2021;17:2706-33.
• 49. Pankhurst MW, Kelley RL, Sanders RL, Woodcock SR, Oorschot DE, Batchelor NJ. Anti-Müllerian hormone overexpression restricts preantral ovarian follicle survival. Journal of endocrinology. 2018;237:153-63.
• 50. Roy S, Gandra D, Seger C et al. Oocyte-Derived Factors (GDF9 and BMP15) and FSH Regulate AMH Expression Via Modulation of H3K27AC in Granulosa Cells. Endocrinology. 2018;159:3433-45.
• 51. Al-SAEDY SH, MTHUWAINI M, Al-SNAFI A. Vitamin D, hormonal and metabolic disturbances in polycystic ovary syndrome. International Journal of Pharmaceutical Research. 2021;13.
• 52. Moridi I, Chen A, Tal O, Tal R. The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis. Nutrients. 2020;12:1567.
• 53. Karimi E, Arab A, Rafiee M, Amani R. A systematic review and meta-analysis of the association between vitamin D and ovarian reserve. Scientific Reports. 2021;11:16005.
• 54. Skowrońska P, Kunicki M, Pastuszek E et al. Vitamin D and anti-Müllerian hormone concentration in human follicular fluid individually aspirated from all patient follicles. Gynecological Endocrinology. 2022;38:28-32.
• 55. Bednarska-Czerwińska A, Olszak-Wąsik K, Olejek A, Czerwiński M, Tukiendorf A. Vitamin D and anti-müllerian hormone levels in infertility treatment: the change-point problem. Nutrients. 2019;11:1053.
• 56. Bacanakgil BH, İlhan G, Ohanoğlu K. Effects of vitamin D supplementation on ovarian reserve markers in infertile women with diminished ovarian reserve. Medicine. 2022;101.
• 57. Chu C, Tsuprykov O, Chen X, Elitok S, Krämer BK, Hocher B. Relationship Between Vitamin D and Hormones Important for Human Fertility in Reproductive-Aged Women. Frontiers in endocrinology. 2021;12:666687-.
• 58. Lerchbaum E, Theiler-Schwetz V, Kollmann M et al. Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial. Nutrients. 2021;13:547.
• 59. Rogenhofer N, Jeschke U, von Schönfeldt V, Mahner S, Thaler CJ. Seasonal dynamic of cholecalciferol (D3) and anti-Muellerian hormone (AMH) with impact on ovarian response and IVF/ICSI. Arch Gynecol Obstet. 2022.