Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-19T20:40:18.552Z Has data issue: false hasContentIssue false
  • English
  • Français

Supplementation of granulosa cells conditioned medium with pyruvate and testosterone could improve early follicular development in cultured 1-day-old mouse ovaries

Published online by Cambridge University Press:  29 April 2021

Mohammad Jafari Atrabi ,
Parimah Alborzi ,
Vahid Akbarinejad  and
Rouhollah Fathi Open the ORCID record for Rouhollah Fathi [Opens in a new window]
Mohammad Jafari Atrabi
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Parimah Alborzi
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Vahid Akbarinejad
Affiliation:
Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Rouhollah Fathi*
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
*
Author for correspondence: Rouhollah Fathi. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. E-mail: rfathi79@royaninstitute.org
Get access Rights & Permissions [Opens in a new window]

Summary

In vitro activation of primordial follicles could serve as a safe method to preserve fertility in patients with cancer subjected to ovarian tissue cryopreservation during oncotherapy, however the culture medium for this purpose requires to be optimized. Granulosa cell conditioned medium (GCCM) has been recognized to enhance primordial follicle activation and the present study was conducted to understand whether addition of pyruvate, a combination of insulin, transferrin and selenium (ITS) or testosterone to GCCM could improve its efficiency in this regard. To this end, 1-day-old mouse ovaries were cultured in four different media including CON (control; containing GGCM only), PYR (containing GCCM plus pyruvate), ITS (containing GCCM plus ITS) or TES (containing GCCM plus testosterone) for 11 days. Furthermore, follicular dynamics and gene expression of factors involved in follicular development were assessed using histological examination and RT-PCR, respectively, on days 5 and 11 of culture. Pyruvate decreased follicular activation, but it enhanced the progression of follicles to the primary stage. Moreover, it upregulated Bmp15 and Cx37 (P < 0.05). In the ITS group, activation of follicles was not affected and total number of follicles was reduced by day 11 of culture. Additionally, ITS downregulated Pi3k, Gdf9, Bmp15 and Cx37 (P < 0.05). Although testosterone did not affect primordial follicle activation, it enhanced the development of follicles up to the preantral stage (P < 0.05). Furthermore, testosterone inhibited the expression of Pten but stimulated the expression of Gdf9 and Cx37 (P < 0.05). In conclusion, the present study revealed that inclusion of pyruvate and testosterone into GCCM could enhance the early development of follicles in cultured 1-day-old mouse ovaries.

Keywords

Granulosa cells conditioned mediumITSMouse ovary culturePyruvateTestosterone
Type
Research Article
Information
Zygote , Volume 29 , Issue 6 , December 2021 , pp. 468 - 475
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alborzi, P, Atrabi, MJ, Akbarinejad, V, Khanbabaei, R and Fathi, R (2020). Incorporation of arginine, glutamine or leucine in culture media accelerates in vitro activation of primordial follicles in one-day-old mouse ovary. Zygote 2020, 1–8.Google Scholar
Amorim, CA and Shikanov, A (2016). The artificial ovary: current status and future perspectives. Future Oncol 12, 2323–32.CrossRefGoogle ScholarPubMed
Atrabi, MJ, Akbarinejad, V, Khanbabaee, R, Dalman, A, Andrade Amorim, C, Najar-Asl, M, Valojerdi, MR and Fathi, R (2019). Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media. J Cell Physiol 234, 10148–56.CrossRefGoogle ScholarPubMed
Bayne, RA, Kinnell, HL, Coutts, SM, He, J, Childs, AJ and Anderson, RA (2015). GDF9 is transiently expressed in oocytes before follicle formation in the human fetal ovary and is regulated by a novel NOBOX transcript. PLoS One 10, e0119819.CrossRefGoogle ScholarPubMed
Biggers, J, Whittingham, D and Donahue, R (1967). The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci USA 58, 560–7.CrossRefGoogle ScholarPubMed
Bockstaele, L, Tsepelidis, S, Dechene, J, Englert, Y and Demeestere, I (2012). Safety of ovarian tissue autotransplantation for cancer patients. Obstet Gynecol Int 2012, 495142.CrossRefGoogle ScholarPubMed
Chae-Kim, JJ and Gavrilova-Jordan, L (2019). Premature ovarian insufficiency: procreative management and preventive strategies. Biomedicines 7, 2.CrossRefGoogle Scholar
Cinco, R, Digman, MA, Gratton, E and Luderer, U (2016). Spatial characterization of bioenergetics and metabolism of primordial to preovulatory follicles in whole ex vivo murine ovary. Biol Reprod 95, 129.CrossRefGoogle ScholarPubMed
Comim, FV, Hardy, K, Robinson, J and Franks, S (2015). Disorders of follicle development and steroidogenesis in ovaries of androgenised foetal sheep. J Endocrinol 225, 39–46.CrossRefGoogle ScholarPubMed
Cook-Andersen, H, Curnow, KJ, Su, HI, Chang, RJ and Shimasaki, S (2016). Growth and differentiation factor 9 promotes oocyte growth at the primary but not the early secondary stage in three-dimensional follicle culture. J Assist Reprod Genet 33, 1067–77.CrossRefGoogle Scholar
Dube, JL, Wang, P, Elvin, J, Lyons, KM, Celeste, AJ and Matzuk, MM (1998). The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 12, 1809–17.CrossRefGoogle ScholarPubMed
Eppig, JJ and O’Brien, MJ (1996). Development in vitro of mouse oocytes from primordial follicles. Biol Reprod 54, 197–207.CrossRefGoogle ScholarPubMed
Fathi, R, Valojerdim, MR, Ebrahimi, B, Eivazkhani, F, Akbarpour, M, Tahaei, LS and Abtahi, NS (2017). Fertility preservation in cancer patients: in vivo and in vitro options. Cell 19, 173–83.Google ScholarPubMed
Findlay, JK, Hutt, KJ, Hickey, M, Anderson, RA (2015). How is the number of primordial follicles in the ovarian reserve established? Biol Reprod 93, 111.CrossRefGoogle Scholar
Fortune, JE, Yang, MY and Muruvi, W (2011). In vitro and in vivo regulation of follicular formation and activation in cattle. Reprod Fertil Dev 23, 15–22.CrossRefGoogle ScholarPubMed
Gilchrist, RB, Lane, M and Thompson, JG (2008). Oocyte-secreted factors: Regulators of cumulus cell function and oocyte quality. Hum Reprod Update 14, 159–77.CrossRefGoogle ScholarPubMed
Harris, SE, Adriaens, I, Leese, HJ, Gosden, RG and Picton, HM (2007). Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro . Reproduction 134, 415–24.CrossRefGoogle ScholarPubMed
Jeruss, JS and Woodruff, TK (2009). Preservation of fertility in patients with cancer. New Engl J Med 360, 902–11.CrossRefGoogle ScholarPubMed
Johnson, MT Freeman, EA, Gardner, DK and Hunt, PA (2007). Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo . Biol Reprod 77, 2–8.CrossRefGoogle ScholarPubMed
Kerr, JB, Duckett, R, Myers, M, Britt, KL, Mladenovska, T and Findlay, JK (2006). Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction 132, 95–109.CrossRefGoogle ScholarPubMed
Kim, SY and Kurita, T (2018). New insights into the role of phosphoinositide 3-kinase activity in the physiology of immature oocytes: lessons from recent mouse model studies. Eur Med J Reprod Health 3, 119–25.Google ScholarPubMed
Luyckx, V, Scalercio, S, Jadoul, P, Amorim, CA, Soares, M, Donnez, J and Dolmans, M-M (2013). Evaluation of cryopreserved ovarian tissue from prepubertal patients after long-term xenografting and exogenous stimulation. Fertil Steril 100, 1350–7, e1353.CrossRefGoogle ScholarPubMed
Magamage, MPS, Zengyo, M, Moniruzzaman, M and Miyano, T (2011). Testosterone induces activation of porcine primordial follicles in vitro . Reprod Med Biol 10, 21–30.CrossRefGoogle ScholarPubMed
McLaughlin, M, Albertini, D, Wallace, W, Anderson, R and Telfer, E (2018). Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol Hum Reprod 24, 135–42.CrossRefGoogle Scholar
Molina, JR, Barton, DL and Loprinzi, CL (2005). Chemotherapy-induced ovarian failure. Drug Safety 28, 401–16.CrossRefGoogle ScholarPubMed
O’Brien, MJ, Pendola, JK and Eppig, JJ (2003). A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biol Reprod 68, 1682–6.CrossRefGoogle ScholarPubMed
Otsuka, F, McTavish, KJ and Shimasaki, S (2011). Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev 78, 9–21.CrossRefGoogle ScholarPubMed
Pepling, ME (2006). From primordial germ cell to primordial follicle: mammalian female germ cell development. Genesis 44, 622–32.CrossRefGoogle ScholarPubMed
Perez-Andujar, A, Newhauser, W, Taddei, P, Mahajan, A and Howell, R (2013). The predicted relative risk of premature ovarian failure for three radiotherapy modalities in a girl receiving craniospinal irradiation. Phys Med Biol 58, 3107.CrossRefGoogle Scholar
Qureshi, AI, Nussey, SS, Bano, G, Musonda, P, Whitehead, SA and Mason, HD (2008). Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries. Reproduction 136, 187–94.CrossRefGoogle ScholarPubMed
Sanfins, A, Rodrigues, P and Albertini, DF (2018). GDF-9 and BMP-15 direct the follicle symphony. J Assist Reprod Genet 35, 1741–50.CrossRefGoogle ScholarPubMed
Simon, AM, Chen, H and Jackson, CL (2006). Cx37 and Cx43 localize to zona pellucida in mouse ovarian follicles. Cell Commun Adhes 13, 61–77.CrossRefGoogle ScholarPubMed
Sugiura, K, Pendola, FL and Eppig, JJ (2005). Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Dev Biol 279, 20–30.CrossRefGoogle ScholarPubMed
Sugiura, K, Su, YQ, Diaz, FJ, Pangas, SA, Sharma, S, Wigglesworth, K, O’Brien, MJ, Matzuk, MM, Shimasaki, S and Eppig, JJ (2007). Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134, 2593–603.CrossRefGoogle ScholarPubMed
Teilmann, SC (2005). Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary. Mol Cell Endocrinol 234, 27–35.CrossRefGoogle ScholarPubMed
Telfer, EE, McLaughlin, M, Ding, C and Thong, KJ (2008). A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum Reprod 23, 1151–8.CrossRefGoogle ScholarPubMed
Torrealday, S, Kodaman, P and Pal, L (2017). Premature ovarian insufficiency – an update on recent advances in understanding and management. F1000Res 6, 2069.CrossRefGoogle ScholarPubMed
Xiao, S, Zhang, J, Romero, MM, Smith, KN, Shea, LD and Woodruff, TK (2015). In vitro follicle growth supports human oocyte meiotic maturation. Sci Rep 5, 17323.CrossRefGoogle ScholarPubMed
Yan, C, Wang, P, DeMayo, J, DeMayo, FJ, Elvin, JA, Carino, C, Prasad, SV, Skinner, SS, Dunbar, BS, Dube, JL, Celeste, AJ and Matzuk, MM (2001). Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15, 854–66.CrossRefGoogle ScholarPubMed
Yang, MY and Fortune, JE (2006). Testosterone stimulates the primary to secondary follicle transition in bovine follicles in vitro . Biol Reprod 75, 924–32.CrossRefGoogle ScholarPubMed
Zhang, H and Liu, K (2015). Cellular and molecular regulation of the activation of mammalian primordial follicles: somatic cells initiate follicle activation in adulthood. Hum Reprod Update 21, 779–86.CrossRefGoogle ScholarPubMed
Zhang, Y, Xu, Y, Kuai, Y, Wang, S, Xue, Q and Shang, J (2016). Effect of testosterone on the Connexin37 of sexual mature mouse cumulus oocyte complex. J Ova Res 9, 82.CrossRefGoogle ScholarPubMed
Zhao, L, Du, X, Huang, K, Zhang, T, Teng, Z, Niu, W, Wang, C and Xia, G (2016). Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice. Sci Rep 6, 23972.CrossRefGoogle ScholarPubMed