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The effect of diet and cardiovascular risk on ovarian aging in cynomolgus monkeys (Macaca fascicularis)

Appt, Susan E. DVM1; Chen, Haiying MD, PhD2; Goode, Amanda K. MA1; Hoyer, Patricia B. PhD3; Clarkson, Thomas B. DVM1; Adams, Michael R. DVM1; Wilson, Mark E. PhD4; Franke, Adrian A. PhD5; Kaplan, Jay R. PhD1

doi: 10.1097/gme.0b013e3181d20cd2

Objective: The aim of this study was to determine the relationships among dietary protein source, cardiovascular risk, reproductive hormones, and ovarian aging.

Methods: Adult female cynomolgus monkeys (Macaca fascicularis) were assigned randomly to one of two diets containing saturated fat and cholesterol, differing only by protein source: (1) casein-lactalbumin (n = 29) or (2) soy protein with isoflavones (n = 32). Cardiovascular risk markers and reproductive hormones were measured at baseline and after 32 months of treatment, at which time the ovaries were removed and serially sectioned and ovarian follicles were counted in every 100th section.

Results: Casein-lactalbumin-fed monkeys had fewer primordial, primary, and secondary follicles (all P values < 0.05) than did their soy-fed counterparts. Antimüllerian hormone was significantly correlated with all follicle types (r values ≥ 0.66, P < 0.001) for casein-fed monkeys and was significantly correlated with primary (rsoy = 0.47, P = 0.005) and secondary (rsoy = 0.45, P = 0.007) follicles in soy-fed monkeys. No significant associations were seen between any of the other reproductive hormones measured and follicle counts. Casein-lactalbumin-fed monkeys had a more atherogenic lipoprotein profile and increased atherosclerosis extent (P < 0.05), but despite these differences in cardiovascular risk between monkeys fed with casein-lactalbumin and monkeys fed with soy, none of the individual cardiovascular risk markers measured in this study explained the relationship between dietary protein source and follicle counts (linear regression, all P values > 0.05).

Conclusions: Diet influences the rate of follicular depletion in cynomolgus macaques; however, the mechanism for this effect remains undetermined.

The present study provides evidence that the source of dietary protein, or isoflavones, affects ovarian reserve in cynomolgus monkeys. These results highlight the importance of nutrition with respect to ovarian aging, although the mechanism underlying this relationship remains to be determined.

1Wake Forest University Primate Center and the Department of Pathology/Comparative Medicine, 2Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; 3Department of Physiology, University of Arizona, Tucson, AZ; 4Yerkes National Primate Research Center and the Division of Psychobiology, Emory University, Atlanta, GA; and 5The Cancer Research Center of Hawaii, Honolulu, HI.

Received September 8, 2009; revised and accepted December 17, 2009.

Funding/support: This work was supported by grant R01 HL079421 from the National Heart, Lung, and Blood Institute (J.R.K.), grant R24 RR022191 (J.R.K.) and S10 RR020890 (A.A.F.) from the National Center for Research Resources, grant R01 AG027847 from the NationalInstitute on Aging (J.R.K.), grant R01 AG021948 from the NationalInstitute on Aging (P.B.H.), and Center Grant ES06694 (P.B.H.).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Susan E. Appt, DVM, Wake Forest University Primate Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail:

©2010The North American Menopause Society