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RESEARCH ARTICLE

Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin

Kari A. Morfeld A B and Janine L. Brown A
+ Author Affiliations
- Author Affiliations

A Center for Species Survival, Smithsonian Conservation Biology Institute, National Zoological Park, 1500 Remount Road, Front Royal, VA 22630, USA.

B Corresponding author. Email: morfeldk@si.edu

Reproduction, Fertility and Development 28(5) 640-647 https://doi.org/10.1071/RD14140
Submitted: 29 April 2014  Accepted: 3 September 2014   Published: 7 November 2014

Abstract

The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world’s largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G : I) between cycling (n = 23; normal 14–16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n = 23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1 = thinnest, 5 = fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G : I ratio than cycling BCS 5 females. Using ‘non-cycling’ as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

Additional keywords: infertility, metabolic hormones, obesity, reproduction.


References

Althabe, F. (2012). Modified risk factors for stillbirth in high-income countries include overweight and obesity, maternal age and smoking. Evid. Based Med. 17, 65–66.
Modified risk factors for stillbirth in high-income countries include overweight and obesity, maternal age and smoking.Crossref | GoogleScholarGoogle Scholar | 21862500PubMed |

Ange, K., Crissey, S. D., Doyle, C., Lance, K., and Hintz, H. (2001). A survey of African (Loxodonta africana) and Asian (Elephas maximus) elephant diets and measured body dimensions compared to their estimated nutrient requirements. In ‘Proceedings of the Nutrition Advisory Group 4th Conference on Zoo and Wildlife Nutrition, Lake Buena Vista’. (Eds M. S. Edwards, K. J. Lisi, M. L Schlegel and R. E. Bray.) pp. 5–14. (San Diego Zoological Society: San Diego.)

Bailey, S. R., Habershon-Butcher, J. L., Ranson, K. J., Elliott, J., and Menzies-Gow, N. J. (2008). Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis. Am. J. Vet. Res. 69, 122–129.
Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht12ltrg%3D&md5=98db9610ad8defefc3368f736ccfc927CAS | 18167097PubMed |

Banks, W. A., Phillips-Conroy, J. W., Jolly, C. J., and Morley, J. E. (2001). Serum leptin levels in wild and captive populations of baboons (papio): implications for the ancestral role of leptin. J. Clin. Endocrinol. Metab. 86, 4315–4320.
Serum leptin levels in wild and captive populations of baboons (papio): implications for the ancestral role of leptin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmvFCku78%3D&md5=5d304379b94c804b079df67096276e45CAS | 11549667PubMed |

Bray, G. A. (1997). Obesity and reproduction. Hum. Reprod. 12, 26–32.
Obesity and reproduction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnsFKnsbc%3D&md5=30a3dbfc3403c76b625bba6438871013CAS | 9403319PubMed |

Brewer, C. J., and Balen, A. H. (2010). The adverse effects of obesity on conception and implantation. Reproduction 140, 347–364.
The adverse effects of obesity on conception and implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1Cnu7fI&md5=3a1d8cc7deb52b8c42689551c760f474CAS | 20395425PubMed |

Brown, J. L. (2000). Reproductive endocrine monitoring of elephants: an essential tool for assisting captive management. Zoo Biol. 19, 347–367.
Reproductive endocrine monitoring of elephants: an essential tool for assisting captive management.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXos12gs7o%3D&md5=69cc31e0a8a3fbe361a8419b0cdae192CAS |

Brown, J. L., and Lehnhardt, J. (1995). Serum and urinary hormones during pregnancy and the peri- and postpartum period in an Asian elephant (Elephas maximus). Zoo Biol. 14, 555–564.
Serum and urinary hormones during pregnancy and the peri- and postpartum period in an Asian elephant (Elephas maximus).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xlsl2ltw%3D%3D&md5=d136a31a3062b13803885cb84c990931CAS |

Brown, J. L., Hildebrandt, T. B., Theison, W., and Neiffer, D. L. (1999a). Endocrine and ultrasound evaluation of a non-cycling African elephant: identification of an ovarian follicular cyst. Zoo Biol. 18, 223–232.
Endocrine and ultrasound evaluation of a non-cycling African elephant: identification of an ovarian follicular cyst.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvVGhsLg%3D&md5=c22d7369565a03785ace05333a31b764CAS |

Brown, J. L., Schmitt, D. J., Bellem, A., Graham, L. H., and Lehnhardt, J. (1999b). Hormone secretion in the Asian elephant (Elephas maximus): characterization of ovulatory and anovulatory luteinizing hormone surges. Biol. Reprod. 61, 1294–1299.
Hormone secretion in the Asian elephant (Elephas maximus): characterization of ovulatory and anovulatory luteinizing hormone surges.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1MvlvVOmsA%3D%3D&md5=8f83f4b5b11ccab2d6076f7ff789dcf8CAS | 10529277PubMed |

Brown, J. L., Olson, D., Keele, M., and Freeman, E. W. (2004a). Survey of the reproductive cyclicity status of Asian and African elephants in North America. Zoo Biol. 23, 309–321.
Survey of the reproductive cyclicity status of Asian and African elephants in North America.Crossref | GoogleScholarGoogle Scholar |

Brown, J. L., Walker, S., and Moeller, T. (2004b). Comparative endocrinology of cycling and noncycling Asian (Elephas maximus) and African (Loxodonta africana) elephants. Gen. Comp. Endocrinol. 136, 360–370.
Comparative endocrinology of cycling and noncycling Asian (Elephas maximus) and African (Loxodonta africana) elephants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjtVegsbg%3D&md5=e9c16e467d218122024a26e0deb77a84CAS | 15081836PubMed |

Bützow, T. L., Lehtovirta, M., Siegberg, R., Hovatta, O., Koistinen, R., Seppalo, M., and Apter, D. (2000). The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. J. Clin. Endocrinol. Metab. 85, 3271–3275.
| 10999821PubMed |

Chang, R. J. (2007). The reproductive phenotype in polycystic ovary syndrome. Nat. Clin. Pract. Endocrinol. Metab. 3, 688–695.
The reproductive phenotype in polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVOgsrnP&md5=768f21e0ab0464c223a56b72cbf2e089CAS | 17893687PubMed |

Clark, A. M., Ledger, W., Galletly, C., Tomlinson, L., Blaney, F., Wang, X., and Norman, R. J. (1995). Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum. Reprod. 10, 2705–2712.
| 1:STN:280:DyaK287mtVGhsw%3D%3D&md5=6407ff060e0961e2b8086d0f8cc63445CAS | 8567797PubMed |

Clark, A. M., Thornley, B., Tomlinson, L., Galletley, C., and Norman, R. J. (1998). Weight loss in obese infertile women results improvement in reproductive outcome for all forms of fertility treatment. Hum. Reprod. 13, 1502–1505.
Weight loss in obese infertile women results improvement in reproductive outcome for all forms of fertility treatment.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1czltFKlug%3D%3D&md5=749f65ae6b5b018044350b3b1e6e3ea4CAS | 9688382PubMed |

Clubb, R., and Mason, G. (2002). ‘A Review of the Welfare of Zoo Elephants in Europe. Report Commissioned by the RSPCA.’ (University of Oxford, Animal Behaviour Research Group: Oxford.)

Clubb, R., Rowcliffe, M., Lee, P., Mar, K. U., Moss, C., and Mason, G. J. (2009). Fecundity and population viability in female zoo elephants: problems and possible solutions. Anim. Welf. 18, 237–247.
| 1:CAS:528:DC%2BD1MXpvFOgtbY%3D&md5=f72e165c5579813d73dae9d9afdd9761CAS |

Codner, E., and Cassorla, F. (2009). Puberty and ovarian function in girls with type 1 diabetes mellitus. Horm. Res. 71, 12–21.
Puberty and ovarian function in girls with type 1 diabetes mellitus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXntFelsQ%3D%3D&md5=66c4805aad84e210fb166e9eb3b642a1CAS | 19039232PubMed |

Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., and Ohannesian, J. P. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292–295.
Serum immunoreactive-leptin concentrations in normal-weight and obese humans.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK287jtlOnsw%3D%3D&md5=30caabc847e5f27108ee5597f29b58c9CAS | 8532024PubMed |

Dale, R. H. (2010). Birth statistics for African (Loxodonta africana) and Asian (Elephas maximus) elephants in human care: history and implications for elephant welfare. Zoo Biol. 29, 87–103.
Birth statistics for African (Loxodonta africana) and Asian (Elephas maximus) elephants in human care: history and implications for elephant welfare.Crossref | GoogleScholarGoogle Scholar | 20391462PubMed |

Dimitroulas, T., Douglas, K. M., Panoulas, V. F., Tomas, T., Smith, J. P., Treharne, G. J., Nightingale, P., Hodson, J., and Kitas, G. D. (2013). Derangement of hemostasis in rheumatoid arthritis: association with demographic, inflammatory and metabolic factors. Clin. Rheumatol. 32, 1357–1364.
Derangement of hemostasis in rheumatoid arthritis: association with demographic, inflammatory and metabolic factors.Crossref | GoogleScholarGoogle Scholar | 23673438PubMed |

Donaldson, M. T., McFarlane, D., Jorgensen, A. J. R., and Beech, J. (2004). Correlation between plasma alpha-melanocyte-stimulating hormone concentration and body mass index in healthy horses. Am. J. Vet. Res. 65, 1469–1473.
Correlation between plasma alpha-melanocyte-stimulating hormone concentration and body mass index in healthy horses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVahsL%2FN&md5=a221506e1a4b71c04e9bca39f4bf1cebCAS | 15566082PubMed |

Dow, T. L., and Brown, J. L. (2012). Evidence that hyperprolactinaemia is associated with ovarian acyclicity in female zoo African elephants. Reprod. Fertil. Dev. 24, 1019–1027.
Evidence that hyperprolactinaemia is associated with ovarian acyclicity in female zoo African elephants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsVKrt77F&md5=73bf2446aea2faa3c5fc42ef19bf331cCAS | 23043790PubMed |

Dow, T. L., Holaskova, I., and Brown, J. L. (2011). Results of the third reproductive assessment survey of North American Asian (Elephas maximus) and African (Loxodonta africana) female elephants. Zoo Biol. 30, 699–711.
Results of the third reproductive assessment survey of North American Asian (Elephas maximus) and African (Loxodonta africana) female elephants.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38%2Flt1GrsQ%3D%3D&md5=2ae7291c751c86f299da3a503a821c81CAS | 21319213PubMed |

Duggal, P. S., Van Der Hoek, K. H., Milner, C. R., Ryan, N. K., Armstrong, D. T., and Magoffin, D. A. (2000). The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology 141, 1971–1976.
| 1:CAS:528:DC%2BD3cXlt1Wnu7o%3D&md5=4c44a3f8bfb8b42c0c78a2edaa276f24CAS | 10830279PubMed |

Faust, L., and Marti, K. (2011). ‘Technical Report on ZooRisk Modeling of the North American African Elephant SSP Population.’ (Lincoln Park Zoo: Chicago.)

Fedorcsák, P., Dale, P. O., Storeng, R., Ertzeik, G., Bjercke, S., Oldereid, N., Omland, A. K., Abyhold, 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 | 15319380PubMed |

Fors, H., Matsuoka, H., Bosaeus, I., Rosberg, S., Wikland, K. A., and Bjarnason, R. (1999). Serum leptin levels correlate with growth hormone secretion and body fat in children. J. Clin. Endocrinol. Metab. 84, 3586–3590.
| 1:CAS:528:DyaK1MXms1OhtLw%3D&md5=d94d143ef8341d732b64d58eef33c27dCAS | 10523000PubMed |

Freeman, E. W., Guagnano, G., Olson, D., Keele, M., and Brown, J. L. (2009). Social factors influence ovarian acyclicity in captive African elephants (Loxodonta africana). Zoo Biol. 28, 1–15.
Social factors influence ovarian acyclicity in captive African elephants (Loxodonta africana).Crossref | GoogleScholarGoogle Scholar | 19358314PubMed |

Gao, Q., and Harvath, T. L. (2008). Cross-talk between estrogen and leptin signaling in the hypothalamus. Am. J. Physiol. Endocrinol. Metab. 294, E817–E826.
Cross-talk between estrogen and leptin signaling in the hypothalamus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlvFCjurg%3D&md5=23c810792b552f7f7f0edd6b0e08ad6cCAS | 18334610PubMed |

Garnsworthy, P. C., Lock, A., Mann, G. E., Sinclair, K. D., and Webb, R. (2008). Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and ovarian function. J. Dairy Sci. 91, 3824–3833.
Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and ovarian function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1SrurrN&md5=a7c8c2d632ebf8ff000b7845286e12b1CAS | 18832204PubMed |

Geor, R., and Frank, N. (2009). Metabolic syndrome: from human organ disease to laminar failure in equids. Vet. Immunol. Immunopathol. 129, 151–154.
Metabolic syndrome: from human organ disease to laminar failure in equids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltVCntLc%3D&md5=6a177d66e172ba064a84e9163add8db3CAS | 19110319PubMed |

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=94abdafaf81fa37c8513fb84dddac0fcCAS | 17095518PubMed |

Goudas, V. T., and Dumesic, D. A. (1997). Polycystic ovary syndrome. Endocrinol. Metab. Clin. North Am. 26, 893–912.
Polycystic ovary syndrome.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c%2FptFKquw%3D%3D&md5=759a102c9aa91081703bc0fae01722a7CAS | 9429864PubMed |

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=b5cb2031f36c5c5a9212357ca6dd38f7CAS | 8173001PubMed |

Hartz, A. J., Barboriak, P. N., Wong, A., Katayama, W. P., and Rimm, A. A. (1979). The association of obesity with infertility and related menstural abnormalities in women. Int. J. Obes. 3, 57–73.
| 1:STN:280:DyaL3c7hsVOgtA%3D%3D&md5=19bb73e21596676a91101835089a1df9CAS | 528119PubMed |

Hatt, J. M., and Clauss, M. (2006). Feeding Asian and African elephants (Elephas maximus and Loxodonta africana) in captivity. Int. Zoo Yearb. 40, 88–95.
Feeding Asian and African elephants (Elephas maximus and Loxodonta africana) in captivity.Crossref | GoogleScholarGoogle Scholar |

Henneke, D. R., Potter, G. D., Kreider, J. L., and Yeates, B. F. (1983). Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet. J. 15, 371–372.
Relationship between condition score, physical measurements and body fat percentage in mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c%2FlslKltg%3D%3D&md5=50d1f0605144b9f9952e050ce3b79992CAS | 6641685PubMed |

Hildebrandt, T. B., Goritz, F., Hermes, R., Reid, C., Dehnhard, M., and Brown, J. L. (2006). Aspects of the reproductive and breeding management of Asian and African elephants. Int. Ybk. 40, 20–40.
Aspects of the reproductive and breeding management of Asian and African elephants.Crossref | GoogleScholarGoogle Scholar |

Hill, J. W., Elmquist, J. K., and Elias, C. F. (2008). Hypothalamic pathways linking energy balance and reproduction. Am. J. Physiol. Endocrinol. Metab. 294, E827–E832.
Hypothalamic pathways linking energy balance and reproduction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlvFCjurk%3D&md5=c343f77845f180439ac544b2a7149297CAS | 18285524PubMed |

Hsueh, A. J., Billig, H., and Tsafriri, A. (1994). Ovarian follicle atresia: a hormonally controlled apoptotic process. Endocr. Rev. 15, 707–724.
| 1:CAS:528:DyaK2MXjs12lsb8%3D&md5=3f18409b017ab4d1de9b58c6e57f7854CAS | 7705278PubMed |

Irvine, L. M., and Shaw, R. W. (2003). The effects of patient obesity in gynaecological practice. Curr. Obstet. Gynaecol. 13, 179–184.
The effects of patient obesity in gynaecological practice.Crossref | GoogleScholarGoogle Scholar |

Johnson, P. J. (2002). The equine metabolic syndrome peripheral Cushing’s syndrome. Vet. Clin. North Am. Equine Pract. 18, 271–293.
The equine metabolic syndrome peripheral Cushing’s syndrome.Crossref | GoogleScholarGoogle Scholar | 15635908PubMed |

Johnson, P. J., Wiedmeyer, C. E., LaCarrubba, A., Ganjam, V. K., and Messer, N. T. (2012). Diabetes, insulin resistance, and metabolic syndrome in horses. J. Diabetes Sci. Technol. 6, 534–540.
Diabetes, insulin resistance, and metabolic syndrome in horses.Crossref | GoogleScholarGoogle Scholar | 22768883PubMed |

Kearns, C. F., McKeever, K. H., John-Alder, H., Abe, T., and Brechue, W. F. (2002). Relationship between body composition, blood volume and maximal oxygen uptake. Equine Vet. J. Suppl. 34, 485–490.
Relationship between body composition, blood volume and maximal oxygen uptake.Crossref | GoogleScholarGoogle Scholar | 12405738PubMed |

Keele, M., and Ediger, N. D. (2011). ‘AZA Elephant Master Plan.’ AZA publication no. 1999 10285.zooe. (Oregon Zoo: Portland.)

Lake, J. K., Power, C., and Cole, T. J. (1997). Women’s reproductive health: the role of body mass index in early and adult life. Int. J. Obes. Relat. Metab. Disord. 21, 432–438.
Women’s reproductive health: the role of body mass index in early and adult life.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szjsFGmuw%3D%3D&md5=7e300a67db9f8461586f47e8afa2d54dCAS | 9192225PubMed |

Lewis, K. D., Shepherdson, D. J., Owens, T. M., and Keele, M. (2010). A survey of elephant husbandry and foot health in North American zoos. Zoo Biol. 29, 221–236.
| 20014111PubMed |

Leyva, F., Godsland, I. F., and Ghatei, M. (1998). Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler. Thromb. Vasc. Biol. 18, 928–933.
Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXktFagt70%3D&md5=58c3e16a72baed47d251482cf8bafc18CAS | 9633933PubMed |

Mácajová, M., Lamosová, D., and Zeman, M. (2004). Role of leptin in farm animals: a review. J. Vet. Med. A Physiol. Pathol. Clin. Med. 51, 157–166.
Role of leptin in farm animals: a review.Crossref | GoogleScholarGoogle Scholar | 15265171PubMed |

Marín-Bevins, C. L., and Olster, D. H. (1999). Food restriction neither improves nor exacerbates reproduction in obese female Zucker rats. Physiol. Behav. 66, 893–897.
Food restriction neither improves nor exacerbates reproduction in obese female Zucker rats.Crossref | GoogleScholarGoogle Scholar |

Martins, M. C., Falerio, L. L., and Fonseca, A. (2012). Relationship between leptin and body mass and metabolic syndrome in an adult population. Rev. Port. Cardiol. 31, 711–719.
Relationship between leptin and body mass and metabolic syndrome in an adult population.Crossref | GoogleScholarGoogle Scholar |

Mason, G. J., and Veasey, J. S. (2010). What do population-level welfare indices suggest about the well-being of zoo elephants? Zoo Biol. 29, 256–273.
| 20140956PubMed |

Matthaei, S., Stumvoll, M., Kellerer, M., and Haring, H. U. (2000). Pathophysiology and pharmacological treatment of insulin resistance. Endocr. Rev. 21, 585–618.
| 1:STN:280:DC%2BD3M7jslKntg%3D%3D&md5=098587f75bb360e99ad54ac279b9cf7cCAS | 11133066PubMed |

Miller, P. B., Forstein, D. A., and Styles, S. (2008). Effect of short-term diet and exercise on hormone levels and menses in obese, infertile women. J. Reprod. Med. 53, 315–319.
| 1:CAS:528:DC%2BD1cXns1amsr8%3D&md5=a75f78a442481c732bbce132d428b063CAS | 18567275PubMed |

Morfeld, K. A., Lehnhardt, J., Alligood, C., Bolling, J., and Brown, J. L. (2014). Development of a body condition scoring index for female African elephants validated by ultrasound measurements of subcutaneous fat. PLoS ONE 9, e93802.
Development of a body condition scoring index for female African elephants validated by ultrasound measurements of subcutaneous fat.Crossref | GoogleScholarGoogle Scholar | 24718304PubMed |

Mouttham, L. L., Buhr, M., Freeman, E. W., Widowski, T. M., Graham, L. H., and Brown, J. L. (2011). Interrelationship of serum testosterone, dominance and ovarian cyclicity status in female African elephants. Anim. Reprod. Sci. 126, 115–121.
Interrelationship of serum testosterone, dominance and ovarian cyclicity status in female African elephants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXosVCku7Y%3D&md5=6bf035bbe133d84db3aacd65770dbdb0CAS | 21592691PubMed |

National Institute for Clinical Excellence (2004). ‘Fertility Update.’ (National Institute for Clinical Excellence: London.)

Norman, R. J., and Clark, A. M. (1998). Obesity and reproductive disorders: a review. Reprod. Fertil. Dev. 10, 55–63.
Obesity and reproductive disorders: a review.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1czpsVGktA%3D%3D&md5=3f39afd966deb58ab2f0617ea73b3859CAS | 9727593PubMed |

Norman, R. J., Noakes, M., Wu, R., Davies, M. J., Moran, L., and Wang, J. X. (2004). Improving reproductive performance in overweight/obese women with effective weight management. Hum. Reprod. Update 10, 267–280.
Improving reproductive performance in overweight/obese women with effective weight management.Crossref | GoogleScholarGoogle Scholar | 15140873PubMed |

Pasquali, R., and Casimirri, F. (1993). The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. Clin. Endocrinol. (Oxf.) 39, 1–16.
The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3szltFehuw%3D%3D&md5=3a0e445dbac2cdc4a724b3b6b20ef506CAS | 8348699PubMed |

Pasquali, R., Pelusi, C., Genghini, S., Cacciari, M., and Gambineri, A. (2003). Obesity and reproductive disorders in women. Hum. Reprod. Update 9, 359–372.
Obesity and reproductive disorders in women.Crossref | GoogleScholarGoogle Scholar | 12926529PubMed |

Poretsky, L., Cataldo, N. A., Rosenwaks, Z., and Giudice, L. C. (1999). The insulin-related ovarian regulatory system in health and disease. Endocr. Rev. 20, 535–582.
The insulin-related ovarian regulatory system in health and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXlvVOnsb0%3D&md5=3e7a17a14143ea4e927003094c5b2de6CAS | 10453357PubMed |

Proctor, C. M., Freeman, E. W., and Brown, J. L. (2010). Results of a second survey to assess the reproductive status of female Asian and African elephants in North America. Zoo Biol. 29, 127–139.
| 20391465PubMed |

Ralston, S. L. (2002). Insulin and glucose regulation. Vet. Clin. North Am. Equine Pract. 18, 295–304.
Insulin and glucose regulation.Crossref | GoogleScholarGoogle Scholar | 15635909PubMed |

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.
Adolescent body mass index and infertility caused by ovulatory disorder.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2czgtlOgsA%3D%3D&md5=5947dce95936b43619b801d66f15b1bdCAS | 8030695PubMed |

Roberts, C. K., Hevener, A. L., and Barnard, R. J. (2013). Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compr. Physiol. 3, 1–58.
| 23720280PubMed |

Rodríguez, F. M., Salvetti, N. R., Panzani, C. G., Barbeito, C. G., Ortega, H. H., and Rey, F. (2011). Influence of insulin-like growth factor-binding proteins-2 and -3 in the pathogenesis of cystic ovarian disease in cattle. Anim. Reprod. Sci. 128, 1–10.
Influence of insulin-like growth factor-binding proteins-2 and -3 in the pathogenesis of cystic ovarian disease in cattle.Crossref | GoogleScholarGoogle Scholar | 21940120PubMed |

Sessions, D. R., Reedy, S. E., Vick, M. M., Murphy, B. A., and Fitzgerald, B. P. (2004). Development of a model for inducing transient insulin resistance in the mare: preliminary implications regarding the estrous cycle. J. Anim. Sci. 82, 2321–2328.
| 1:CAS:528:DC%2BD2cXmtFeltb0%3D&md5=cd59361e7da59f30fccc211c554464f2CAS | 15318731PubMed |

Strong, A. L., Strong, T., Rhodes, L., Semon, J. A., Zhang, X., Zhenzhen, S., Shijia, Z., Gimble, J. M., Burow, M. E., and Bunnell, B. A. (2013). Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways. Breast Cancer Res. 15, R102.
Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways.Crossref | GoogleScholarGoogle Scholar | 24176089PubMed |

Tamer Erel, C., and Senturk, L. M. (2009). The impact of body mass index on assisted reproduction. Curr. Opin. Obstet. Gynecol. 21, 228–235.
The impact of body mass index on assisted reproduction.Crossref | GoogleScholarGoogle Scholar | 19395966PubMed |

Tena-Sempere, M. (2007). Roles of ghrelin and leptin in the control of reproductive function. Neuroendocrinology 86, 229–241.
Roles of ghrelin and leptin in the control of reproductive function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Kjtr%2FI&md5=038772e1319d516be562cb4d62eb1184CAS | 17851226PubMed |

Vick, M. M., Sessions, D. R., Murphy, B. A., Kennedy, E. L., Reedy, E., and Fitzgerald, B. P. (2006). Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity. Reprod. Fertil. Dev. 18, 609–617.
Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xms1ersbk%3D&md5=5074c6696b4a7cb6f863f2e1cb3aba44CAS | 16930507PubMed |

Vick, M. M., Adams, A. A., Murphy, B. A., Sessions, D. R., Horohov, D. W., Cook, R. F., and Shelton, B. J. (2007). Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. J. Anim. Sci. 85, 1144–1155.
Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksF2htLo%3D&md5=36f06511a9f9d56ec7b207bd0bcc32edCAS | 17264235PubMed |

Wade, G. N., Schneider, J. E., and Li, H. Y. (1996). Control of fertility by metabolic cues. Am. J. Physiol. 270, E1–E19.
| 1:CAS:528:DyaK28XhtVynsr8%3D&md5=de1dd299aa639304c5256cf501887eedCAS | 8772468PubMed |

Willis, D., Mason, H., Gilling-Smith, C., and Frank, S. (1996). Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J. Clin. Endocrinol. Metab. 81, 302–309.
| 1:CAS:528:DyaK28XkvVyqug%3D%3D&md5=db696aa583b4bcf74ed6f9a43413c0dfCAS | 8550768PubMed |