The impact of obesity on oocytes: evidence for lipotoxicity mechanisms
Linda L.-Y. Wu A , Robert J. Norman A and Rebecca L. Robker A B
+ Author Affiliations
- Author Affiliations
A The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
B Corresponding author. Email: rebecca.robker@adelaide.edu.au
Reproduction, Fertility and Development 24(1) 29-34 https://doi.org/10.1071/RD11904
Published: 6 December 2011
Abstract
Obesity can have detrimental effects on pregnancy rates in natural conceptions and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This review summarises the most recent clinical literature investigating whether obesity impacts oocyte quality and early embryo growth. In other tissues, obesity leads to lipotoxicity responses including endoplasmic reticulum stress, mitochondrial dysfunction and apoptosis. Recent reports indicate that lipotoxicity is a mechanism by which obesity may impact oocyte quality.
Additional keywords: endoplasmic reticulum stress, palmitate.
References
Aardema, H., Vos, P. L., Lolicato, F., Roelen, B. A., Knijn, H. M., Vaandrager, A. B., Helms, J. B., and Gadella, B. M. (2011). Oleic acid prevents detrimental effects of saturated fatty acids on bovine oocyte developmental competence. Biol. Reprod. 85, 62–69.| Oleic acid prevents detrimental effects of saturated fatty acids on bovine oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotFOls74%3D&md5=9bf74be82533275f9a36a6981f11dbebCAS |
Awartani, K. A., Nahas, S., Al Hassan, S. H., Al Deery, M. A., and Coskun, S. (2009). Infertility treatment outcome in sub groups of obese population. Reprod. Biol. Endocrinol. 7, 52.
| Infertility treatment outcome in sub groups of obese population.Crossref | GoogleScholarGoogle Scholar |
Bausenwein, J., Serke, H., Eberle, K., Hirrlinger, J., Jogschies, P., Hmeidan, F. A., Blumenauer, V., and Spanel-Borowski, K. (2010). Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women. Mol. Hum. Reprod. 16, 117–124.
| Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXktlCjuw%3D%3D&md5=7b4fc7fcc1bbfced9516f1c92660bf65CAS |
Bellver, J., Ayllon, Y., Ferrando, M., Melo, M., Goyri, E., Pellicer, A., Remohi, J., and Meseguer, M. (2010). Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil. Steril. 93, 447–454.
| Female obesity impairs in vitro fertilization outcome without affecting embryo quality.Crossref | GoogleScholarGoogle Scholar |
Bender, K., Walsh, S., Evans, A. C., Fair, T., and Brennan, L. (2010). Metabolite concentrations in follicular fluid may explain differences in fertility between heifers and lactating cows. Reproduction 139, 1047–1055.
| Metabolite concentrations in follicular fluid may explain differences in fertility between heifers and lactating cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXns12qsbs%3D&md5=ff5024631d313e20abbc79b01d8fd3fdCAS |
Breckenridge, D. G., Germain, M., Mathai, J. P., Nguyen, M., and Shore, G. C. (2003). Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22, 8608–8618.
| Regulation of apoptosis by endoplasmic reticulum pathways.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptFOmtbk%3D&md5=43c1e94fb43dc21972cf014d173a217bCAS |
Cnop, M., Hannaert, J. C., Hoorens, A., Eizirik, D. L., and Pipeleers, D. G. (2001). Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50, 1771–1777.
| Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlslKnu74%3D&md5=407d6b10c0ae698cbb549e9f399fd38fCAS |
Esinler, I., Bozdag, G., and Yarali, H. (2008). Impact of isolated obesity on ICSI outcome. Reprod. Biomed. Online 17, 583–587.
| Impact of isolated obesity on ICSI outcome.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cnlvFygtw%3D%3D&md5=fa32d3865b59ccde71022bbde3bc7baeCAS |
Fedorcsak, P., Dale, P. O., Storeng, R., Ertzeid, G., Bjercke, S., Oldereid, N., Omland, A. K., Abyholm, T., and Tanbo, T. (2004). Impact of overweight and underweight on assisted reproduction treatment. Hum. Reprod. 19, 2523–2528.
| Impact of overweight and underweight on assisted reproduction treatment.Crossref | GoogleScholarGoogle Scholar |
Garris, D. R. (2005). Ovarian follicular lipoapoptosis: structural, cytochemical and metabolic basis of reproductive tract atrophy following expression of the hypogonadal diabetes (db/db) syndrome. Reprod. Toxicol. 20, 31–38.
| Ovarian follicular lipoapoptosis: structural, cytochemical and metabolic basis of reproductive tract atrophy following expression of the hypogonadal diabetes (db/db) syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXivFSisLY%3D&md5=2105777d0442126833d9993993fa8f51CAS |
Gesink Law, D. C., Maclehose, R. F., and Longnecker, M. P. (2007). Obesity and time to pregnancy. Hum. Reprod. 22, 414–420.
| Obesity and time to pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2s%2FhvFCktA%3D%3D&md5=5d27a3cd32172baa41fadc51432d745fCAS |
Grodstein, F., Goldman, M. B., and Cramer, D. W. (1994). Body mass index and ovulatory infertility. Epidemiology 5, 247–250.
| Body mass index and ovulatory infertility.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c3islWltg%3D%3D&md5=16b6cea535c8bcfd3365dba1f2a7e367CAS |
Hill, M. J., Hong, S., and Frattarelli, J. L. (2011). Body mass index impacts in vitro fertilization stimulation. ISRN Obstet. Gynecol. 2011, 929251.
| Body mass index impacts in vitro fertilization stimulation.Crossref | GoogleScholarGoogle Scholar |
Igosheva, N., Abramov, A. Y., Poston, L., Eckert, J. J., Fleming, T. P., Duchen, M. R., and McConnell, J. (2010). Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS ONE 5, e10074.
| Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.Crossref | GoogleScholarGoogle Scholar |
Jensen, T. K., Scheike, T., Keiding, N., Schaumburg, I., and Grandjean, P. (1999). Fecundability in relation to body mass and menstrual cycle patterns. Epidemiology 10, 422–428.
| Fecundability in relation to body mass and menstrual cycle patterns.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1MzivVejtw%3D%3D&md5=1e8e85faa30a20127848ef7749f7815cCAS |
Jungheim, E. S., Schoeller, E. L., Marquard, K. L., Louden, E. D., Schaffer, J. E., and Moley, K. H. (2010). Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring. Endocrinology 151, 4039–4046.
| Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1Oju7rN&md5=c59f4f61ea442fc0ca6c5f02f3574d1bCAS |
Jungheim, E. S., Louden, E. D., Chi, M. M., Frolova, A. I., Riley, J. K., and Moley, K. H. (2011a). Preimplantation exposure of mouse embryos to palmitic acid results in fetal growth restriction followed by catch-up growth in the offspring Biol Reprod. , .
Jungheim, E. S., Macones, G. A., Odem, R. R., Patterson, B. W., Lanzendorf, S. E., Ratts, V. S., and Moley, K. H. (2011b). Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertil. Steril. 95, 1970–1974.
| Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltFymt7s%3D&md5=881394caab6ed1c5b685d8cb0adfdaafCAS |
Leroy, J. L., Vanholder, T., Mateusen, B., Christophe, A., Opsomer, G., de Kruif, A., Genicot, G., and Van Soom, A. (2005). Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro. Reproduction 130, 485–495.
| Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFent7rJ&md5=28b8e4b714ca8128dba0a3e5acb8b0b5CAS |
Li, Y., Yang, D., and Zhang, Q. (2010). Impact of overweight and underweight on IVF treatment in Chinese women. Gynecol. Endocrinol. 26, 416–422.
| Impact of overweight and underweight on IVF treatment in Chinese women.Crossref | GoogleScholarGoogle Scholar |
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., and Schaffer, J. E. (2003). Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. USA 100, 3077–3082.
| Triglyceride accumulation protects against fatty acid-induced lipotoxicity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXisVCnsLs%3D&md5=69f7beac378388f350db806da407d289CAS |
Luke, B., Brown, M. B., Stern, J. E., Missmer, S. A., Fujimoto, V. Y., and Leach, R. (2011). Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum. Reprod. 26, 245–252.
| Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates.Crossref | GoogleScholarGoogle Scholar |
Maheshwari, A., Stofberg, L., and Bhattacharya, S. (2007). Effect of overweight and obesity on assisted reproductive technology–a systematic review. Hum. Reprod. Update 13, 433–444.
| Effect of overweight and obesity on assisted reproductive technology–a systematic review.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2svnvVKgsA%3D%3D&md5=d58b6d6f696ec3a364a666a97c33df34CAS |
Malhotra, J. D., and Kaufman, R. J. (2007). Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid. Redox Signal. 9, 2277–2294.
| Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1GrsLzL&md5=38fdce30d0946d99fdb47a46adda68f1CAS |
Marquard, K.L., Stephens, S.M., Jungheim, E.S., Ratts, V.S., Odem, R.R., Lanzendorf, S., and Moley, K.H. (2011). Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil. Steril. 95, 2146–2149.e1.
Martinuzzi, K., Ryan, S., Luna, M., and Copperman, A. B. (2008). Elevated body mass index (BMI) does not adversely affect in vitro fertilization outcome in young women. J. Assist. Reprod. Genet. 25, 169–175.
| Elevated body mass index (BMI) does not adversely affect in vitro fertilization outcome in young women.Crossref | GoogleScholarGoogle Scholar |
Matalliotakis, I., Cakmak, H., Sakkas, D., Mahutte, N., Koumantakis, G., and Arici, A. (2008). Impact of body mass index on IVF and ICSI outcome: a retrospective study. Reprod. Biomed. Online 16, 778–783.
| Impact of body mass index on IVF and ICSI outcome: a retrospective study.Crossref | GoogleScholarGoogle Scholar |
McCormick, B., Thomas, M., Maxwell, R., Williams, D., and Aubuchon, M. (2008). Effects of polycystic ovarian syndrome on in vitro fertilization-embryo transfer outcomes are influenced by body mass index. Fertil. Steril. 90, 2304–2309.
| Effects of polycystic ovarian syndrome on in vitro fertilization-embryo transfer outcomes are influenced by body mass index.Crossref | GoogleScholarGoogle Scholar |
Metwally, M., Cutting, R., Tipton, A., Skull, J., Ledger, W. L., and Li, T. C. (2007). Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod. Biomed. Online 15, 532–538.
| Effect of increased body mass index on oocyte and embryo quality in IVF patients.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2sjgslWruw%3D%3D&md5=e88bbbcdc8e291fff4f0cea036568a73CAS |
Minge, C. E., Bennett, B. D., Norman, R. J., and Robker, R. L. (2008). Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality. Endocrinology 149, 2646–2656.
| Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Gmsb%2FO&md5=c300ee70125853a914f07c599717216aCAS |
Moran, L., and Teede, H. (2009). Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum. Reprod. Update 15, 477–488.
| Metabolic features of the reproductive phenotypes of polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXntF2hs74%3D&md5=7bc854628d3b1255d46cb65e75b4aa1fCAS |
Orvieto, R., Meltcer, S., Nahum, R., Rabinson, J., Anteby, E. Y., and Ashkenazi, J. (2009). The influence of body mass index on in vitro fertilization outcome. Int. J. Gynaecol. Obstet. 104, 53–55.
| The influence of body mass index on in vitro fertilization outcome.Crossref | GoogleScholarGoogle Scholar |
Ozcan, U., Cao, Q., Yilmaz, E., Lee, A. H., Iwakoshi, N. N., Ozdelen, E., Tuncman, G., Gorgun, C., Glimcher, L. H., and Hotamisligil, G. S. (2004). Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457–461.
| Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.Crossref | GoogleScholarGoogle Scholar |
Ozcan, L., Ergin, A. S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M. G., and Ozcan, U. (2009). Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 9, 35–51.
| Endoplasmic reticulum stress plays a central role in development of leptin resistance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptFWquw%3D%3D&md5=aa2668dce6f26d10b783e637d394ef42CAS |
Rich-Edwards, J. W., Goldman, M. B., Willett, W. C., Hunter, D. J., Stampfer, M. J., Colditz, G. A., and Manson, J. E. (1994). Adolescent body mass index and infertility caused by ovulatory disorder. Am. J. Obstet. Gynecol. 171, 171–177.
| 1:STN:280:DyaK2czgtlOgsA%3D%3D&md5=02dd4e31cf93e3f648e0788a4a86670fCAS |
Rich-Edwards, J. W., Spiegelman, D., Garland, M., Hertzmark, E., Hunter, D. J., Colditz, G. A., Willett, W. C., Wand, H., and Manson, J. E. (2002). Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology 13, 184–190.
| Physical activity, body mass index, and ovulatory disorder infertility.Crossref | GoogleScholarGoogle Scholar |
Robker, R. L. (2008). Evidence that obesity alters the quality of oocytes and embryos. Pathophysiology 15, 115–121.
| Evidence that obesity alters the quality of oocytes and embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXpt1Kjurs%3D&md5=34c8ab82683da443c7d93193a595d080CAS |
Robker, R. L., Akison, L. K., Bennett, B. D., Thrupp, P. N., Chura, L. R., Russell, D. L., Lane, M., and Norman, R. J. (2009). Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J. Clin. Endocrinol. Metab. 94, 1533–1540.
| Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlvVCqtrw%3D&md5=6dbea83daa67f3b7ff7a916b7ec93c6cCAS |
Robker, R. L., Yang, X., Wu, L. L., Lane, M., and Norman, R. J. (2011). Follicle fluid of obese women induces endoplasmic reticulum stress in cumulus-oocyte complexes and blocks oocyte maturation. Endocr. Rev. 32, P1-291.
Shah, D. K., Missmer, S. A., Berry, K. F., Racowsky, C., and Ginsburg, E. S. (2011). Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet. Gynecol. 118, 63–70.
| Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization.Crossref | GoogleScholarGoogle Scholar |
Sneed, M. L., Uhler, M. L., Grotjan, H. E., Rapisarda, J. J., Lederer, K. J., and Beltsos, A. N. (2008). Body mass index: impact on IVF success appears age-related. Hum. Reprod. 23, 1835–1839.
| Body mass index: impact on IVF success appears age-related.Crossref | GoogleScholarGoogle Scholar |
Spandorfer, S. D., Kump, L., Goldschlag, D., Brodkin, T., Davis, O. K., and Rosenwaks, Z. (2004). Obesity and in vitro fertilization: negative influences on outcome. J. Reprod. Med. 49, 973–977.
van der Steeg, J. W., Steures, P., Eijkemans, M. J., Habbema, J. D., Hompes, P. G., Burggraaff, J. M., Oosterhuis, G. J., Bossuyt, P. M., van der Veen, F., and Mol, B. W. (2008). Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum. Reprod. 23, 324–328.
| Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women.Crossref | GoogleScholarGoogle Scholar |
Vilarino, F. L., Christofolini, D. M., Rodrigues, D., de Souza, A. M., Christofolini, J., Bianco, B., and Barbosa, C. P. (2011). Body mass index and fertility: is there a correlation with human reproduction outcomes? Gynecol. Endocrinol. 27, 232–236.
| Body mass index and fertility: is there a correlation with human reproduction outcomes?Crossref | GoogleScholarGoogle Scholar |
Wass, P., Waldenstrom, U., Rossner, S., and Hellberg, D. (1997). An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer. Hum. Reprod. 12, 2057–2060.
| An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c%2FivVemuw%3D%3D&md5=d3d19445e043e3af6fa711e63a7704b6CAS |
Wu, L. L., Dunning, K. R., Yang, X., Russell, D. L., Lane, M., Norman, R. J., and Robker, R. L. (2010). High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology 151, 5438–5445.
| High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVKks7bL&md5=977b6a60fa2feca2c1d2436652aa5f28CAS |
Wu, L. L., Russell, D. L., Norman, R. J., and Robker, R. L. (2011). Elucidation of mechanisms by which fatty acids impair oocyte quality and fertilization. The Society for Reproductive Biology [Abstract]
Zaadstra, B. M., Seidell, J. C., Van Noord, P. A., te Velde, E. R., Habbema, J. D., Vrieswijk, B., and Karbaat, J. (1993). Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. BMJ 306, 484–487.
| Fat and female fecundity: prospective study of effect of body fat distribution on conception rates.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s7pt1KqsA%3D%3D&md5=06873d6ee5b7ed05e57d34de8c036e22CAS |
Zhang, D., Zhu, Y., Gao, H., Zhou, B., Zhang, R., Wang, T., Ding, G., Qu, F., Huang, H., and Lu, X. (2010). Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women. Gynecol. Endocrinol. 26, 325–332.
| Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women.Crossref | GoogleScholarGoogle Scholar |
