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Leptin decreases apoptosis and promotes the activation of primordial follicles through the phosphatidylinositol-3-kinase/protein kinase B pathway in cultured ovine ovarian tissue

Published online by Cambridge University Press:  28 April 2021

T.J.S. Macedo
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
V.G. Menezes
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
R.S. Barberino
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
R.L.S. Silva
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
B.B. Gouveia
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
A.P.O. Monte
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
T.L.B.G. Lins
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
J.M.S. Santos
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
M.É.S. Bezerra
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
A. Wischral
Affiliation:
Laboratory of Animal Reproduction, Federal Rural University of Pernambuco, Recife-PE, Brazil
M.A.A. Queiroz
Affiliation:
Laboratory of Bromatology and Animal Nutrition, Federal University of São Francisco Valley, Petrolina, PE, Brazil
G.G.L. Araújo
Affiliation:
Embrapa Semi-Arid, Petrolina, PE, Brazil
A.M. Batista
Affiliation:
Laboratory of Animal Reproduction, Federal Rural University of Pernambuco, Recife-PE, Brazil
M.H.T. Matos*
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, PetrolinaPE, Brazil
*
Author for correspondence: M.H.T. Matos. Universidade Federal do Vale do São Francisco (UNIVASF), Campus de Ciências Agrárias. Colegiado de Medicina Veterinária, Laboratório de Biologia Celular, Citologia e Histologia, Rodovia BR 407, Km 12, Lote 543, Projeto de Irrigação Nilo Coelho, S/N, C1, CEP: 56300–990, PetrolinaPE, Brasil. Tel: +55 87 2101 4839. E-mail: helena.matos@univasf.edu.br

Summary

This study evaluated the effects of leptin on primordial follicle survival and activation after in vitro culture of ovine ovarian tissue and if leptin acts through the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) pathway. Ovarian fragments were fixed for histology (fresh control) or cultured for 7 days in control medium (α-MEM+) alone or supplemented with leptin (1, 5, 10, 25 or 50 ng/ml). Follicle morphology, activation and apoptosis were analyzed. Next, the fragments were cultured in the medium that showed the best results in the absence or the presence of the PI3K inhibitor (LY294002), and immunohistostaining of p-Akt protein was assessed. After culture, the percentage of normal follicles decreased (P < 0.05) in all treatments compared with the fresh control. Moreover, control medium and 1 ng/ml leptin had similar (P > 0.05) percentages of normal follicles, which were significantly higher than those in other treatments. However, culture with 1 ng/ml leptin maintained apoptosis similarly (P > 0.05) to that of the fresh control and lower (P < 0.05) than that in α-MEM+. Leptin did not influence follicle activation (P > 0.05) compared with the control medium (α-MEM+). Culture in 1 ng/ml leptin with LY294002 decreased the normal follicles and increased apoptosis, inhibited follicle activation (P < 0.05), and reduced p-Akt immunostaining, compared with the medium containing 1 ng/ml leptin without PI3K inhibitor. In conclusion, leptin at 1 ng/ml reduces apoptosis and promotes the activation of primordial follicles compared with the fresh control after in vitro culture of ovine ovarian tissue possibly through the PI3K/Akt pathway.

Type
Research Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Adhikari, D, Risal, S, Liu, K and Shen, Y (2013). Pharmacological inhibition of mTORC1 prevents over-activation of the primordial follicle pool in response to elevated PI3K signalling. PLoS One 8, e53810.CrossRefGoogle Scholar
Aragonès, G, Ardid-Ruiz, A, Ibars, M, Suárez, M and Bladé, C (2016). Modulation of leptin resistance by food compounds. Mol Nutr Food Res 60, 1789–803.CrossRefGoogle ScholarPubMed
Batista, AM, Silva, DM, Rêgo, MJ, Silva, FL, Silva, EC, Beltrão, EI, Gomes Filho, MA, Wischral, A and Guerra, MM (2013). The expression and localization of leptin and its receptor in goat ovarian follicles. Anim Reprod Sci 141, 142–7.CrossRefGoogle ScholarPubMed
Bedaiwy, MA and Hussein, MR (2004). Histological evaluation and in situ localization of apoptosis in fresh and cryopreserved ovarian tissue Middle East Fertil Soc J 9, 163–70.Google Scholar
Bilbao, MG, Di Yorio, MP, Galarza, RA, Varone, CL and Faletti, AG (2015). Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats. Reproduction 149, 357–66.CrossRefGoogle ScholarPubMed
Boelhauve, M, Sinowatz, F, Wolf, E and Fabíola, PL (2005). Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts. Biol Reprod 73, 737–44.CrossRefGoogle ScholarPubMed
Braw-Tal, R (2002). The initiation of follicle growth: the oocyte or the somatic cells? Mol Cell Endocrinol 187, 11–8.CrossRefGoogle ScholarPubMed
Bus, A, Langbeen, A, Martin, B, Leroy, JLMR and Bols, PEJ (2019). Is the pre-antral ovarian follicle the ‘holy grail’ for female fertility preservation? Anim Reprod Sci 207, 119–30.CrossRefGoogle Scholar
Cecconi, S, Mauro, A, Cellini, V and Patacchiola, F (2012). The role of Akt signalling in the mammalian ovary. Int J Dev Biol 56, 809–17.CrossRefGoogle ScholarPubMed
Chaves, RN, Martins, FS, Saraiva, MV, Celestino, JJ, Lopes, CA, Correia, JC, Verde, IB, Matos, MH, Báo, SN, Name, KP, Campello, CC, Silva, JR and Figueiredo, JR (2008). Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro. Reprod Fertil Dev 20, 640–7.CrossRefGoogle ScholarPubMed
Chen, C, Chang, YC, Lan, MS and Breslin, M (2013). Leptin stimulates ovarian cancer cell growth and inhibits apoptosis by increasing cyclin D1 and Mcl-1 expression via the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. Int J Oncol 42, 1113–9.CrossRefGoogle ScholarPubMed
Cirillo, D, Rachiglio, AM, la Montagna, R, Giordano, A and Normanno, N (2008). Leptin signaling in breast cancer: an overview. J Cell Biochem 105, 956–64.CrossRefGoogle ScholarPubMed
Craig, J, Zhu, H, Dyce, PW, Petrik, J and Li, J (2004). Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway. Endocrinology 145, 5355–63.CrossRefGoogle ScholarPubMed
Devos, M, Grosbois, J and Demeestere, I (2020). Interaction between PI3K/AKT and Hippo pathways during in vitro follicular activation and response to fragmentation and chemotherapy exposure using a mouse immature ovary model. Biol Reprod 102, 717–29.CrossRefGoogle ScholarPubMed
Figueiredo, JR, Cadenas, J, Lima, LF and Santos, RR (2019). Advances in in vitro folliculogenesis in domestic ruminants. Anim Reprod 16, 5265.CrossRefGoogle Scholar
Fruhbeck, G (2006). Intracellular signalling pathways activated by leptina. Biochem J 393, 720.CrossRefGoogle Scholar
Gharbi, SI, Zvelebil, MJ, Shuttleworth, SJ, Hancox, T, Saghir, N, Timms, JF and Waterfield, MD (2007). Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J 404, 1521.CrossRefGoogle ScholarPubMed
Ghasemi, A, Saeidi, J, Azimi-Nejad, M and Hashemy, SI (2019). Leptin-induced signaling pathways in cancer cell migration and invasion. Cell Oncol 42, 243–60.CrossRefGoogle ScholarPubMed
Guerreiro, DD, Lima, LF, Rodrigues, GQ, Carvalho Ade, A, Castro, SV, Campello, CC, Pessoa Cdo, Ó, Gadelha, CR, Figueiredo, JR, Bordignon, V and Rodrigues, AP (2016). In situ cultured preantral follicles is a useful model to evaluate the effect of anticancer drugs on caprine folliculogenesis. Microsc Res Tech 79, 773–81.CrossRefGoogle ScholarPubMed
Guerreiro, DD, Mbemya, GT, Bruno, JB, Faustino, LR, de Figueiredo, JR and Rodrigues, APR (2019). In vitro culture systems as an alternative for female reproductive toxicology studies. Zygote 27, 5563.CrossRefGoogle ScholarPubMed
Jin, YX, Cui, XS, Han, YJ and Kim, NH (2009). Leptin accelerates pronuclear formation following intracytoplasmic sperm injection of porcine oocytes: possible role for MAP kinase inactivation. Anim Reprod Sci 115, 137–48.CrossRefGoogle ScholarPubMed
Jones, ASK and Shikanov, A (2019). Follicle development as an orchestrated signaling network in a 3D organoid. J Biol Eng 13, 2. CrossRefGoogle Scholar
Kamalamma, P, Kona, SS, Praveen Chakravarthi, V, Siva Kumar, AV, Punyakumari, B and Rao, VH (2016). Effect of leptin on in vitro development of ovine preantral ovarian follicles. Theriogenology 85, 224–9.CrossRefGoogle ScholarPubMed
Keshrawani, S, Aruna Kumari, G and Reddy, KRC (2016). Supplementation of leptin on in vitro maturation of sheep oocytes. Asian J Anim Vet Adv 11, 629–36.CrossRefGoogle Scholar
Kumar, PA, Sivakumar, AVN, Pathipati, D, Chakravarthi, VP, Brahmaiah, KV and Rao, VH (2019). Leptin induced in vitro development of ovarian follicles in sheep is related to the expression of P450 aromatase and steroidogenesis. Theriogenology 136, 16.CrossRefGoogle ScholarPubMed
Langbeen, A, Ginneken, CV, Fransen, E, Bosmans, E, Leroy, JLMR and Bols, PEJ (2016). Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model. Anim Reprod Sci 168, 7385.CrossRefGoogle Scholar
Lin, XH, Wang, H, Wu, DD, Ullah, K, Yu, TT, Ur Rahman, T and Huang, HF (2017). High leptin level attenuates embryo development in overweight/obese infertile women by inhibiting proliferation and promotes apoptosis in granule cell. Horm Metab Res 49, 534541.Google ScholarPubMed
Lunardi, FO, de Aguiar, FLN, Apolloni, LB, Duarte, ABG, de Sá, NAR, Leal, ÉSS, Sales, AD, Lobo, CH, Campello, CC, Smitz, J, Apgar, GA, de Figueiredo, JR and Rodrigues, APR (2017). Sheep isolated secondary follicles are able to produce metaphase II oocytes after vitrification and long-term in vitro growth. Biopreserv Biobank 15, 321–31.CrossRefGoogle ScholarPubMed
Macedo, TJS, Santos, JMS, Bezerra, MÉS, Menezes, VG, Gouveia, BB, Barbosa, LMR, Lins, TLBG, Monte, APO, Barberino, RS, Batista, AM, Barros, VRP, Wischral, A, Queiroz, MAA, Araújo, GGL and Matos, MHT (2019). Immunolocalization of leptin and its receptor in the sheep ovary and in vitro. Mol Cell Endocrinol 495, 110506. CrossRefGoogle ScholarPubMed
Menezes, VG, Monte, APO, Gouveia, BB, Lins, TLBG, Donfack, NJ, Macedo, TJS, Barberino, RS, Santos, JM, Matos, MHT, Batista, AM and Wischral, A (2019). Effects of leptin on the follicular development and mitochondrial activity of ovine isolated early antral follicles cultured in vitro. Theriogenology 138, 7783.CrossRefGoogle ScholarPubMed
Moniruzzaman, M, Lee, J, Zengyo, M and Miyano, T (2010). Knockdown of FOXO3 induces primordial oocyte activation in pigs. Reproduction 139, 337–48.CrossRefGoogle ScholarPubMed
Panda, BSK, Pandey, S, Somal, A, Parmar, MS, Bhat, IA, Baiju, I, Bharti, MK, Sai Kumar, G, Chandra, V and Sharma, GT (2017). Leptin supplementation in vitro improved developmental competence of buffalo oocytes and embryos. Theriogenology 98, 116–22.CrossRefGoogle ScholarPubMed
Pérez-Pérez, A, Toro, AR, Vilarino-Garcia, T, Guadix, P, Maymó, JL, Dueñas, JL, Varone, CL and Sánchez-Margalet, V (2016). Leptin reduces apoptosis triggered by high temperature in human placental villous explants: the role of the p53 pathway. Placenta 42, 106–13.CrossRefGoogle ScholarPubMed
Picton, HM (2001). Activation of follicle development: the primordial follicle. Theriogenology 55, 1193–210.CrossRefGoogle ScholarPubMed
Reddy, P, Adhikari, D, Zheng, W, Liang, S, Hämäläinen, T, Tohonen, V, Ogawa, W, Noda, T, Volarevic, S, Huhtaniemi, I and Liu, K (2009). PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Hum Mol Genet 18, 2813–24.CrossRefGoogle ScholarPubMed
Santos, JMS, Lins, TLBG, Barberino, RS, Menezes, VG, Gouveia, BB and Matos, MHT (2019). Kaempferol promotes primordial follicle activation through the phosphatidylinositol 3-kinase/protein kinase B signaling pathway and reduces DNA fragmentation of sheep preantral follicles cultured in vitro. Mol Reprod Dev 86, 319–29.CrossRefGoogle ScholarPubMed
Shafiei Sheykhani, HR, Batavani, RA and Najafi, GR (2016). Protective effect of leptin on induced apoptosis with trichostatin A on buffalo oocytes. Vet Res Forum 7, 99104.Google ScholarPubMed
Seoane-Collazo, P, Martínez-Sánchez, N, Milbank, E and Contreras, C (2020). Incendiary leptin. Nutrients 12, 472. CrossRefGoogle ScholarPubMed
Shea, LD, Woodruff, TK and Shikanov, A (2014). Bioengineering the ovarian follicle microenvironment. Ann Rev Biomed Eng 16, 2952.CrossRefGoogle ScholarPubMed
Silva, JR, van den Hurk, R, Costa, SH, Andrade, ER, Nunes, AP, Ferreira, FV, Lôbo, RN and Figueiredo, JR (2004). Survival and growth of goat primordial follicles after in vitro culture of ovarian cortical slices in media containing coconut water. Anim Reprod Sci 81(3–4), 273–86.CrossRefGoogle ScholarPubMed
Stefansdottir, A, Fowler, PA, Powles-Glover, N, Anderson, RA and Spears, N (2014). Use of ovary culture techniques in reproductive toxicology. Reprod Toxicol 49, 117–35.CrossRefGoogle ScholarPubMed
Taskin, AC, Kocabay, A, Ebrahimi, A, Karahuseyinoglu, S, Sahin, GN, Ozcimen, B, Ruacan, A and Onder, TT (2019). Leptin treatment of in vitro cultured embryos increases outgrowth rate of inner cell mass during embryonic stem cell derivation. In Vitro Cell Dev Biol Anim 55, 473–81.CrossRefGoogle ScholarPubMed
Telfer, EE (2019). Future developments: in vitro growth (IVG) of human ovarian follicles. Acta Obstet Gynecol Scand 98, 653–8.CrossRefGoogle ScholarPubMed
Tsai, M, Asakawa, A, Amitani, H and Inui, A (2012). Stimulation of leptin secretion by insulin. Indian J Endocrinol Metabol 16, S5438.Google ScholarPubMed
Wen, R, Hu, S, Xiao, Q, Han, C, Gan, C, Gou, H, Liu, H, Li, L, Xu, H, He, H and Wang, J (2015). Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway. J Steroid Biochem 149, 70–9.CrossRefGoogle ScholarPubMed
Zhang, H, Risal, S, Gorre, N, Busayavalasa, K, Li, X, Shen, Y, Bosbach, B, Brännström, M and Liu, K (2014). Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice. Curr Biol 24, 2501–8.CrossRefGoogle ScholarPubMed
Zhao, Q, Ma, Y, Sun, NX, Ye, C, Zhang, Q, Sun, SH, Xu, C, Wang, F and Li, W (2014). Exposure to bisphenol A at physiological concentrations observed in Chinese children promotes primordial follicle growth through the PI3K/Akt pathway in an ovarian culture system. Toxicol In Vitro 28, 1424–9.CrossRefGoogle Scholar
Zhou, J, Peng, X and Mei, S (2019). Autophagy in ovarian follicular development and atresia. Int J Biol Sci 15, 726–37.CrossRefGoogle ScholarPubMed
Zieba, DA, Biernat, W and Barć, J (2020). Roles of leptin and resistin in metabolism, reproduction, and leptin resistance. Domest Anim Endocrinol 73, 106472. CrossRefGoogle ScholarPubMed
Zwirska-Korczala, K, Adamczyk-Sowa, M, Sowa, P, Pilc, K, Suchanek, R, Pierzchala, K, Namyslowski, G, Misiolek, M, Sodowski, K, Kato, I, Kuwahara, A and Zabielski, R (2007). Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 58(Suppl 1), 5364.Google ScholarPubMed