Acta Scientific Women's Health (ASWH)(ISSN: 2582-3205)

Review Article Volume 4 Issue 2

An Update on the Role of Bone Morphogenetic Protein and Growth Differentiation Factor on Follicular Generation in Human Menstrual Cycle with Clinical Impact on ART Success and PCOS Pathogenesis/Therapy-a Systematic Review

Kulvinder Kochar Kaur1*, Gautam Allahbadia2 and Mandeep Singh3

1Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India
2Scientific Director, Ex-Rotunda-A Centre for Human Reproduction, Mumbai, India
3Consultant Neurologist, Swami Satyanand Hospital, Jalandhar, Punjab, India

*Corresponding Author: Kulvinder Kochar Kaur, Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India.

Received: January 21, 2022; Published: January 31, 2022

Abstract

Background: With the initiaI identification of capacity of generation of heterotopic bone Bone morphogenetic proteins (BMP) represent growth factors that possess numerous functions from the transforming growth factor beta (TGF-β) super family, With the utilization of cellular along with molecular genetic approaches, more recently studies have implied that that intraovarian BMP ‘s work as robust functional controllers of ovarian follicular function. The crosstalk that takes place in a `bidirectional manner of the oocytes besides the somatic cells surrounding them is a must for the normal follicular generation along with maturation of the oocytes. Thus we reviewed the existent information regarding the physiological part as well as the molecular determining factors of these ovarian controlling factors amongst the germline somatic -controlling loop.

Aim: The control of ovarian function has been ill characterized amongst humans, as whereas the elemental event of follicular generation along with maturation of the oocytes is akin in different species, with maximum knowledge in the context of control of ovarian follicular function gets derived via rodent studies. Hence the concentration was on studies where utilization of human biological materials done for getting insight in the context of human ovarian biology for the generation of strategies with the aim of avoidance, diagnosis therapy treatment, diagnosis besides treatment of these aberrations.

Methods and Results: The outcomes studies with utilization of human biological materials documented the expression of BMP ‘s or GDF’s in addition to their respective receptors along with their molecular signaling in the basic cells (oocytes, cumulus/granulosa cells (GCs) besides theca/stroma cells) of the ovarian follicles right through generation. On the existence of recombinant BMP ‘s/GDF’s along with generation the physiological functional part of human intraovarian BMP ‘s/GDF’s have been illustrated in each aspect of function of ovary ranging from i) follicle generation ii) steroidogenesis iicell-cell contact, iv) maturation of the oocytes v) ovulation and luteal function. Moreover, crosstalk amongst these ovarian controllers and endocrine signaling system. Impairment or natural mutations amongst the BMP system might result in numerous female reproductive diseases. With the generation of recombinant BMP, synthetic BMP inhibitors, gene therapy, tools meant for BMP ligand concealment, has seen to it that the BMP pathway has become a probable therapeutic target in some fertility pathological disorders. Nevertheless, further clinical trials are required. More recently GDF 8 has been demonstrated to be an intraovarian factor that might play an innovative part in control of ovarian functions in human ovary.

Keywords: Bone Morphogenetic; Follicular Generation; Ovulation; PCOS; Physiological; Endocrine

References

  1. Knight PG and Glister C. “TGF-beta superfamily members and ovarian follicle development”. Reproduction 132 (2006): 191-206.
  2. Wagner DO., et al. “BMPs: from Bone-to-Bone morphogenetic proteins”. Science Signaling 3 (2010): mr1.
  3. Rossi RO., et al. “The Bone morphogenetic protein system and the regulation of ovarian follicle development in mammals”. Zygote 24 (2016): 1-17.
  4. Qin Y., et al. “Genetics of primary ovarian insufficiency: new developments and opportunities”. Human Reproduction Update 21 (2015): 787-808.
  5. Rider CC and Mulloy B. “Bone morphogenetic protein and Growth Differentiation factor and cytokine families and their protein antagonists”. Biochemical Journal 429 (2010): 1-12.
  6. Chang HM., et al. “Oocyte somatic cell interactions in the human ovary-a novel role of Bone morphogenetic proteins and Growth Differentiation factors”. Human Reproduction Update 1 (2017): 1-1-8.
  7. Veitia RA and Caburet S. “Extensive sequence turnover of the Signal members of GDF/ BMP family: exploring their evolutionary landscape”. Biology Direct 4 (2009): 22.
  8. McIntosh CJ., et al. “The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and GDF9”. Biology of Reproduction 79 (2008): 889-896.
  9. Seidah NG and Prat A. “The biology and the therapeutic targeting of proproteins convertases”. Nature Reviews Drug Discovery 11 (2012): 367-383.
  10. Harrison CA., et al. “Prodomains regulate the synthesis, extracellular localization and activity of TGF-beta superfamily ligands”. Growth Factors 29 (2011): 174-186.
  11. Peng J., et al. “Growth Differentiation factor9, Bone morphogenetic protein 15 heterodimers are potent regulators of ovarian function”. Proceedings of the National Academy of Sciences of the United States of America 110 (2013): E776-785.
  12. Persani L., et al. “The fundamental role of Bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders”. Human Reproduction Update 20 (2014): 869-883.
  13. Miyagi M., et al. “BMP2, BMP4, noggin, BMPR1A, BMPR1B, and BMPRII are differentially expressed in the adult rat spinal cord”. Neuroscience 203 (2012): 12-26.
  14. Mueller TD and Nickel J. “Promiscuity and specificity in BMP receptor activation”. FEBS Letters 586 (2012): 1846-1859.
  15. Holdzhausen A., et al. “Novel Bone morphogenetic protein signaling through Smad 2 and Smad 3 to regulate cancer progression and development”. The FASEB Journal 28 (2014): 1248-1267.
  16. Zhang H., et al. “Differential activation of non-canonical signaling of SMAD2/SMAD3 by Bone morphogenetic proteins causes disproportionate hyaluronan production in immortalized granulosa cells”. Molecular and Cellular Endocrinology 428 (2016): 17-27.
  17. Yamaguchi K., et al. “Identification of the MAPKKK family as a potential mediator of TGF-beta signal Transduction”. Science 270 (1995): 2008-2011.
  18. Fang L., et al. “Growth Differentiation factor 8 decreases StAR expression through ALK5 mediated Smad 3 and ERK1/2 signaling pathways in luteinized granulosa cells”. Endocrinology 156 (2015): 4284-4294.
  19. Bayasula Iwase A., et al. “Establishment of a human non luteinized granulosa cell lines that transitions from the gonadotrophins independent to the gonadotrophins dependent status”. Endocrinology 153 (2012): 42851-42860.
  20. Fang L., et al. “TGF-beta 1 increases lysyl oxidase expression by down regulating MIR29A in human granulose-lutei n cells”. Reproduction 152 (2016): 205-213.
  21. Chang HM., et al. “Recombinant BMP4 and BMP7 downregulate pentraxin 3 in human granulosa cells”. The Journal of Clinical Endocrinology and Metabolism 100 (2015a): E365-374.
  22. Chang HM., et al. “Recombinant BMP4 and BMP7 increase activin A production by up regulating inhibin beta subunit and furin expression in human granulose-lutein cells”. The Journal of Clinical Endocrinology and Metabolism 100 (2015c): E375-386.
  23. Chang HM., et al. “Activin A induced increase in LOX activity in human granulose-lutein cells is mediated by CTGF”. Reproduction 152 (2016a): 293-301.
  24. Chang HM., et al. “Connective tissue growth factor mediates Growth Differentiation factor 8- induced increase of lysyl oxidase activity in human granulose-lutein cells”. Molecular and Cellular Endocrinology 434 (2016c): 186-198.
  25. Li Y., et al. “Increased GDF 9 and BMP 15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization and embryo quality in humans”. Reproductive Biology and Endocrinology 12 (2014): 81.
  26. Khalaf M., et al. “BMP system expression in GCs from Polycystic ovary syndrome 13 women and the in vitro effects of BMP4, BMP6, and BMP7 in GCs steroidogenesis”. European Journal of Endocrinology 168 (2013): 437-444.
  27. Kristensen SG., et al. “Expression of TGF-beta superfamily growth factors, their receptors, the associated SMAD 3 antagonists in five size matched populations of preantral follicles from normal human ovaries”. Molecular Human Reproduction 20 (2014): 293-308.
  28. Nio-Kobayashi J., et al. “Bone morphogenetic proteins are mediators of luteolysis in the human corpus luteum”. Endocrinology 156 (2015): 1494-1503.
  29. Qiao J and Feng HL. “Extra and intra intraovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence”. Human Reproduction Update 17 (2011): 17-33.
  30. Regan SL., et al. “Dys regulation of granulosa bone morphogenetic protein receptor 1 B density is associated with reduced ovarian reserve and the age-related decline in human fertility”. Molecular and Cellular Endocrinology 425 (2016): 84-93.
  31. Childs AJ., et al. “BMP signaling in the human fetal ovary is developmentally regulated and promotes Primordial Germ Cell apoptosis”. Stem Cells 28 (2010): 1368-1378.
  32. Chang HM., et al. “Oocyte derived BMP15 but not GDF9 down regulate connexin 43 expression and decrease gap junction inter cellular communication activity in immortalized human granulosa cells”. Molecular Human Reproduction 20 (2014): 373-383.
  33. Eppig JJ. “Oocyte control of ovarian follicular development and function in mammals”. Reproduction 122 (2001): 829-838.
  34. Chang HM., et al. “Effects of Recombinant activin on steroidogenesis in human granulose-lutein cells”. The Journal of Clinical Endocrinology and Metabolism 99 (2014b): E1922-1932.
  35. Fang L., et al. “EGF like growth factors induce COX2 derived PGE2production through ERK1/2in human granulosa human granulosa cells”. The Journal of Clinical Endocrinology and Metabolism 2013;98 (2013): 4932-4941.
  36. Chang HM., et al. “BMP15 suppresses progesterone generation by down regulating StAR via ALK3 in human granulose-lutein cells”. Molecular Endocrinology 27 (2013): 2093-2104.
  37. Zhang H., et al. “BMP4 and BMP7 suppress StAR and progesterone production via ALK3 and SMAD 1/5/8- SMAD 4 in Human granulose-lutei n cells”. Endocrinology 156 (2015): 4269-4280.
  38. Wigglesworth K., et al. “Transcriptomic diver sificatication of developing cumulus and mural cells in mouse ovarian follicles”. Biology of Reproduction 92 (2015): 23.
  39. Baranova NS., et al. “Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix crosslinking”. Journal of Biological Chemistry 289 (2014): 30481-30498.
  40. Wei LN., et al. “Reduced and delayed expression of GDF 9 and BMP 15 in ovarian tissue in women with Polycystic ovary syndrome”. The Journal of Assisted Reproduction and Genetics 31 (2014): 1483-1490.
  41. Asghari R., et al. “Alterations of TGFB1, GDF9and BMPR2 gene expression in preantral follicles of an estradio valerate induced Polycystic ovary syndrome mouse model can lead to anovulation, Polycystic morphology, obesity and absence of hyperandrogenism”. Clinical and Experimental Reproductive Medicine 3 (2021): 245-254.
  42. Simpson CM., et al. “Aberrant GDF9 expression and activation are associated with common human ovarian disorders”. The Journal of Clinical Endocrinology and Metabolism 99 (2014): E615-624.
  43. Chang HM., et al. “Effect of Growth Differentiation factor8 on steroidogenesis in human granulosa-lutein cells”. Fertility and Sterility 2016b;105 (2016b): 520-528.
  44. Chang HM., et al. “Activin A, B and AB decrease progesterone product ion by downregulating StAR in human granulose-lutein cells”. Molecular and Cellular Endocrinology 412 (2015b): 290-301.
  45. Luo X., et al. “Bone morphogenetic protein inhibits Growth Differentiation factor induced cell signaling via up regulation of gremlin 2 expression in human granulosa-lutein cells”. Reproductive Biology and Endocrinology 19 (2021): 173.
  46. Bai L., et al. “The exploration of poor ovarian reserve-related risk factors:a potential role of Growth Differentiation factor8 in predicting ovarian response in IVF-ET patient”. Frontiers in Endocrinology 12 (2021): 708089.
  47. Gong Y., et al. “Age related decline in the expression of GDF 9 and BMP 15 genes in the folliclefluid and granulosa cells derived from poor ovarian responders”. Journal of Ovarian Research 14 (2021): 1.
  48. Turathum B., et al. “The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization”. Cells 10 (2021): 2292.
  49. Magro-Lopez E and Munoz-Fernandes. “The role of BMP signaling in female reproductive system development and function”. International Journal of Molecular Sciences 22 (2021): 11927.
  50. Bai L., et al. “Aberrant elevations of GDF8impairs granulose cell glucose metabolism via up regulating SERPINE expression in patients with PCOS”. Molecular Therapy - Nucleic Acids 23 (2021): 294-309.

Citation

Citation: Kulvinder Kochar Kaur., et al. “An Update on the Role of Bone Morphogenetic Protein and Growth Differentiation Factor on Follicular Generation in Human Menstrual Cycle with Clinical Impact on ART Success and PCOS Pathogenesis/Therapy-a Systematic Review". Acta Scientific Women's Health 4.2 (2022): 58-72.

Copyright

Copyright: © 2022 Kulvinder Kochar Kaur., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




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