Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Age-associated changes in granulosa cell transcript abundance in equine preovulatory follicles

Dawn R. Sessions-Bresnahan A B and Elaine M. Carnevale A C
+ Author Affiliations
- Author Affiliations

A Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

B Present address: Berry College, PO Box 495003, Mount Berry, GA 30149-5003, USA.

C Corresponding author. Email: elaine.carnevale@colostate.edu

Reproduction, Fertility and Development 27(6) 906-913 https://doi.org/10.1071/RD14467
Submitted: 25 November 2014  Accepted: 17 February 2015   Published: 17 March 2015

Abstract

Age-related changes in follicle paracrine signalling are not defined, and follicular gene transcript abundance could predict oocyte viability. Granulosa cells from preovulatory follicles of mares considered Young (n = 12; 4–14 years), Mid-aged (n = 9; 15–19 years) and Old (n = 14; 20–27 years) were evaluated for transcript abundance related to systemic and follicle-specific pathways. Gene transcript abundance for receptors of insulin, adiponectin and peroxisome proliferating factor-γ were higher or tended to be higher in Mid-aged or Old than Young mares. Transcript abundance for interleukin (IL)-6 was elevated in Old versus Young mares, and IL-6 signal transducer was elevated in Old versus younger groups. Expression of tumour necrosis factor (TNF) receptor superfamily member 1A was higher in Mid-aged than Young mares, whereas TNF-inducible gene 6 protein mRNA tended to decrease in Mid-aged versus Young and Old mares. Genes for LH receptor and steroidogenic acute regulatory protein tended to be increased in Old versus Mid-aged and Young mares, respectively. Young and Old mares had higher mRNA for tissue-type plasminogen activator than Mid-aged mares. Thioredoxin-2 mRNA was higher in Old than younger groups. We observed age-related changes in mRNA of receptors for metabolic hormones, inflammatory processes, steroidogenic hormones, tissue remodelling and mitochondrial function, which could contribute to and/or mark alterations in follicular function and fertility.

Additional keywords: follicular maturation, inflammation, metabolism, mitochondrial stress, steroidogenesis, tissue remodelling.


References

Acevedo, N., Ding, J., and Smith, G. D. (2007). Insulin signaling in mouse oocytes. Biol. Reprod. 77, 872–879.
Insulin signaling in mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Cnu77I&md5=2da0592138676b6d7abd2c4c83909ef6CAS | 17625112PubMed |

Altun, T., Jindal, S., Greenseid, K., Shu, J., and Pal, L. (2011). Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. J. Assist. Reprod. Genet. 28, 245–251.
Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy.Crossref | GoogleScholarGoogle Scholar | 21046223PubMed |

Baranao, J. L., and Hammond, J. M. (1984). Comparative effects of insulin and insulin-like growth factors on DNA synthesis and differentiation of porcine granulosa cells. Biochem. Biophys. Res. Commun. 124, 484–490.
Comparative effects of insulin and insulin-like growth factors on DNA synthesis and differentiation of porcine granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXmt1ehs7Y%3D&md5=ce985344881f34ee8c0bb6636569f214CAS | 6093801PubMed |

Carnevale, E. M. (2008). The mare model for follicular maturation and reproductive aging in the woman. Theriogenology 69, 23–30.
The mare model for follicular maturation and reproductive aging in the woman.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVSmu7nN&md5=b1d730b243c0636c9f9498a2aecbc1f0CAS | 17976712PubMed |

Carnevale, E. M., Bergfelt, D. R., and Ginther, O. J. (1993). Aging effects of follicular activity and concentrations of FSH, LH, and progesterone in mares. Anim. Reprod. Sci. 31, 287–299.
Aging effects of follicular activity and concentrations of FSH, LH, and progesterone in mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXltV2nsb0%3D&md5=447aae172b61b197d75fb8805cae2dfaCAS |

Carnevale, E. M., Maclellan, L. J., Coutinho da Silva, M. A., Scott, T. J., and Squires, E. L. (2000). Comparison of culture and insemination techniques for equine oocyte transfer. Theriogenology 54, 981–987.
Comparison of culture and insemination techniques for equine oocyte transfer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M%2Fot1Cisw%3D%3D&md5=88d00f25912447b6f17486cab9450e8cCAS | 11097049PubMed |

de Bruin, J. P., Dorland, M., Spek, E. R., Posthuma, G., van Haaften, M., Looman, C. W., and te Velde, E. R. (2004). Age-related changes in the ultrastructure of the resting follicle pool in human ovaries. Biol. Reprod. 70, 419–424.
Age-related changes in the ultrastructure of the resting follicle pool in human ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnsl2jsQ%3D%3D&md5=9dacbd3dad7969b2c0ae63d066409881CAS | 14561658PubMed |

Eppig, J. J., and O’Brien, M. (1995). In vitro maturation and fertilization of oocytes isolated from aged mice: a strategy to rescue valuable genetic resources. J. Assist. Reprod. Genet. 12, 269–273.
In vitro maturation and fertilization of oocytes isolated from aged mice: a strategy to rescue valuable genetic resources.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28%2FlvFKmuw%3D%3D&md5=56aa89f86ffeca7be138095c08a4601eCAS | 7580024PubMed |

Ershler, W. B., and Keller, E. T. (2000). Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu. Rev. Med. 51, 245–270.
Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXisVelsbY%3D&md5=eb95e7247bf7c1668991455232a53c30CAS | 10774463PubMed |

Fajas, L., Debril, M. B., and Auwerx, J. (2001). Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J. Mol. Endocrinol. 27, 1–9.
Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmtlCrtbw%3D&md5=07494e043563e7a967eff4157d1e7fb3CAS | 11463572PubMed |

Fülöp, C., Kamath, R. V., Li, Y., Otto, J. M., Salustri, A., Olsen, B. R., Glant, T. T., and Hascall, V. C. (1997). Coding sequence, exon–intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes. Gene 202, 95–102.
Coding sequence, exon–intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes.Crossref | GoogleScholarGoogle Scholar | 9427551PubMed |

Fülöp, C., Szántó, S., Mukhopadhyay, D., Bárdos, T., Kamath, R. V., Rugg, M. S., Day, A. J., Salustri, A., Hascall, V. C., Glant, T. T., and Mikecz, K. (2003). Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development 130, 2253–2261.
Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice.Crossref | GoogleScholarGoogle Scholar | 12668637PubMed |

Ginther, O. J., and Bergfelt, D. R. (1992). Associations between FSH concentrations and major and minor follicular waves in pregnant mares. Theriogenology 38, 807–821.
Associations between FSH concentrations and major and minor follicular waves in pregnant mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvF2nsQ%3D%3D&md5=ba9a27280de01e870df5df803a1670c8CAS | 16727181PubMed |

Ginther, O. J., Gastal, E. L., Gastal, M. O., Bergfelt, D. R., Baerwald, A. R., and Pierson, R. A. (2004). Comparative study of the dynamics of follicular waves in mares and women. Biol. Reprod. 71, 1195–1201.
Comparative study of the dynamics of follicular waves in mares and women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnvVGqtLo%3D&md5=1cea972231e85796c187aa4e767ad3a9CAS | 15189824PubMed |

Glass, D., Vinuela, A., Davies, M. N., Ramasamy, A., Parts, L., Knowles, D., Brown, A. A., Hedman, A. K., Small, K. S., Buil, A., Grundberg, E., Nica, A. C., Di Meglio, P., Nestle, F. O., Ryten, M., Durbin, R., McCarthy, M. I., Deloukas, P., Dermitzakis, E. T., Weale, M. E., Bataille, V., and Spector, T. D. (2013). Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biol. 14, R75.
Gene expression changes with age in skin, adipose tissue, blood and brain.Crossref | GoogleScholarGoogle Scholar | 23889843PubMed |

Healy, D. L., Trouson, A. O., and Andersen, A. N. (1994). Female infertility: causes and treatment. Lancet 343, 1539–1544.
Female infertility: causes and treatment.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c3ns1KrsA%3D%3D&md5=4faebccd04bb87f6292d1fe06ebdb76fCAS | 7911874PubMed |

Hsieh, M., Lee, D., Panigone, S., Horner, K., Chen, R., Theologis, A., Lee, D. C., Threadgill, D. W., and Conti, M. (2007). Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Mol. Cell. Biol. 27, 1914–1924.
Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXit1Wgu74%3D&md5=be93cc934352fca4b72bf486bd6342ddCAS | 17194751PubMed |

Klein, N. A., Battaglia, D. E., Woodruff, T. K., Padmanabhan, V., Giudice, L. C., Bremner, W. J., and Soules, M. R. (2000). Ovarian follicular concentrations of activin, follistatin, inhibin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3, and vascular endothelial growth factor in spontaneous menstrual cycles of normal women of advanced reproductive age. J. Clin. Endocrinol. Metab. 85, 4520–4525.
| 1:CAS:528:DC%2BD3MXis1CmsQ%3D%3D&md5=ca3bf2599af2a9b95512b48ce62a9511CAS | 11134102PubMed |

Ledoux, S., Campos, D. B., Lopes, F. L., Dobias-Goff, M., Palin, M. F., and Murphy, B. D. (2006). Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology 147, 5178–5186.
Adiponectin induces periovulatory changes in ovarian follicular cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFCgsL3E&md5=780dbbc5db2c097a932fd952164b297fCAS | 16916953PubMed |

Li, M., Karakji, E. G., Xing, R., Fryer, J. N., Carnegie, J. A., Rabbani, S. A., and Tsang, B. K. (1997). Expression of urokinase-type plasminogen activator and its receptor during ovarian follicular development. Endocrinology 138, 2790–2799.
| 1:CAS:528:DyaK2sXktVKgsrg%3D&md5=5d3c8614f60315580cca58fddcd53b82CAS | 9202219PubMed |

Lim, J., and Luderer, U. (2011). Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary. Biol. Reprod. 84, 775–782.
Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjvFanu7s%3D&md5=eec782bd39451450c8f7010a225bd8d2CAS | 21148108PubMed |

Liu, Z., de Matos, D. G., Fan, H. Y., Shimada, M., Palmer, S., and Richards, J. S. (2009). Interleukin-6: an autocrine regulator of the mouse cumulus cell–oocyte complex expansion process. Endocrinology 150, 3360–3368.
Interleukin-6: an autocrine regulator of the mouse cumulus cell–oocyte complex expansion process.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXotlCrsbg%3D&md5=81fdba836dc043793a221c43f8b2f369CAS | 19299453PubMed |

Lovekamp-Swan, T., and Chaffin, C. L. (2005). The peroxisome proliferator-activated receptor gamma ligand troglitazone induces apoptosis and p53 in rat granulosa cells. Mol. Cell. Endocrinol. 233, 15–24.
The peroxisome proliferator-activated receptor gamma ligand troglitazone induces apoptosis and p53 in rat granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXitlCit7k%3D&md5=6bb7b0424e70a0e26c73158f8246ec2aCAS | 15767042PubMed |

Madill, S. (2002). Reproductive considerations: mare and stallion. Vet. Clin. North Am. Equine Pract. 18, 591–619.
Reproductive considerations: mare and stallion.Crossref | GoogleScholarGoogle Scholar | 12516936PubMed |

Matoba, S., Bender, K., Fahey, A. G., Mamo, S., Brennan, L., Londergan, P., and Fair, T. (2014). Predictive value of bovine follicular components as markers of oocyte developmental potential. Reprod. Fertil. Dev. 26, 337–345.
Predictive value of bovine follicular components as markers of oocyte developmental potential.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXjtFCmtg%3D%3D&md5=8eae6be14f9b9332b909d0b368e84058CAS | 23514964PubMed |

Ny, T., Bjersing, L., Hsueh, A. J., and Loskutoff, D. J. (1985). Cultured granulosa cells produce two plasminogen activators and an antiactivator, each regulated differently by gonadotropins. Endocrinology 116, 1666–1668.
Cultured granulosa cells produce two plasminogen activators and an antiactivator, each regulated differently by gonadotropins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2MXhsl2ntLo%3D&md5=0f6d7e2d85ea0249776ffc9e059b829dCAS | 3918858PubMed |

Park, J. Y., Su, Y. Q., Ariga, M., Law, E., Jin, S. L., and Conti, M. (2004). EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science 303, 682–684.
EGF-like growth factors as mediators of LH action in the ovulatory follicle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmvVKlsg%3D%3D&md5=5d954a7ad7a1fe0e2878c16ac4ee2563CAS | 14726596PubMed |

Poretsky, L., and Kalin, M. F. (1987). The gonadotropic function of insulin. Endocr. Rev. 8, 132–141.
The gonadotropic function of insulin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXltV2gtLw%3D&md5=435aaa94d18c9df1149e80921f3904d3CAS | 3301317PubMed |

Roubenoff, R., Harris, T. B., Abad, L. W., Wilson, P. W., Dallal, G. E., and Dinarello, C. A. (1998). Monocyte cytokine production in an elderly population: effect of age and inflammation. J. Gerontol. A Biol. Sci. Med. Sci. 53A, M20–M26.
Monocyte cytokine production in an elderly population: effect of age and inflammation.Crossref | GoogleScholarGoogle Scholar |

Russell, D. L., and Robker, R. L. (2007). Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum. Reprod. Update 13, 289–312.
Molecular mechanisms of ovulation: co-ordination through the cumulus complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmtlCisbc%3D&md5=1e06188007ef054c9e97ae3f7cf6eae2CAS | 17242016PubMed |

Sayasith, K., Dore, M., and Sirois, J. (2007). Molecular characterization of tumor necrosis alpha-induced protein 6 and its human chorionic gonadotropin-dependent induction in theca and mural granulosa cells of equine preovulatory follicles. Reproduction 133, 135–145.
Molecular characterization of tumor necrosis alpha-induced protein 6 and its human chorionic gonadotropin-dependent induction in theca and mural granulosa cells of equine preovulatory follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjs1aju7g%3D&md5=7f765109f0a6120fa54ff1cb3b2f2865CAS | 17244740PubMed |

Schoppee, P. D., Garmey, J. C., and Veldhuis, J. D. (2002). Putative activation of the peroxisome proliferator-activated receptor gamma impairs androgen and enhances progesterone biosynthesis in primary cultures of porcine theca cells. Biol. Reprod. 66, 190–198.
Putative activation of the peroxisome proliferator-activated receptor gamma impairs androgen and enhances progesterone biosynthesis in primary cultures of porcine theca cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xht1yrsQ%3D%3D&md5=6179e6b9d47fc2afa8832d42b9a8681dCAS | 11751282PubMed |

Shigenaga, M. K., Hagen, T. M., and Ames, B. N. (1994). Oxidative damage and mitochondrial decay in aging. Proc. Natl Acad. Sci. USA 91, 10 771–10 778.
Oxidative damage and mitochondrial decay in aging.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXmvFyjtL4%3D&md5=d5737fece840ef48be6b3d4666685182CAS |

Spicer, L. J., Alpizar, E., and Echternkamp, S. E. (1993). Effects of insulin, insulin-like growth factor I, and gonadotropins on bovine granulosa cell proliferation, progesterone production, estradiol production, and(or) insulin-like growth factor I production in vitro. J. Anim. Sci. 71, 1232–1241.
| 1:CAS:528:DyaK3sXks1els7s%3D&md5=09e0d5e14f87c21b6b5bc8bd62137881CAS | 8505257PubMed |

Tabandeh, M. R., Hosseini, A., Saeb, M., Kafi, M., and Saeb, S. (2010). Changes in the gene expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in ovarian follicular cells of dairy cow at different stages of development. Theriogenology 73, 659–669.
Changes in the gene expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in ovarian follicular cells of dairy cow at different stages of development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitVOhsr4%3D&md5=6bcef271c0f76a643e49ab1ab5a172aaCAS | 20047754PubMed |

Tang, B., Matsuda, T., Akira, S., Nagata, N., Ikehara, S., Hirano, T., and Kishimoto, T. (1991). Age-associated increase in interleukin 6 in MRL/lpr mice. Int. Immunol. 3, 273–278.
Age-associated increase in interleukin 6 in MRL/lpr mice.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M3msFCltg%3D%3D&md5=d622d7c904e7ce451589d6ad679867acCAS | 2049341PubMed |

Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., Ito, Y., Kamon, J., Tsuchida, A., Kumagai, K., Kozono, H., Hada, Y., Ogata, H., Tokuyama, K., Tsunoda, M., Ide, T., Murakami, K., Awazawa, M., Takamoto, I., Froguel, P., Hara, K., Tobe, K., Nagai, R., Ueki, K., and Kadowaki, T. (2007). Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med. 13, 332–339.
| 1:CAS:528:DC%2BD2sXisVKku7g%3D&md5=d9997e75f4907d40de7ef41d670c8f86CAS | 17268472PubMed |

Zhang, H., Go, Y. M., and Jones, D. P. (2007). Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress. Arch. Biochem. Biophys. 465, 119–126.
Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpsFGhtLo%3D&md5=314b945492d4c74198dde4b3f541f1baCAS | 17548047PubMed |