Western style diet with and without chronic androgen treatment alters the number structure and function of small antral follicles in ovaries of young adult monkeys

Capsule:
Consumption of a Western-style diet by female nonhuman primates with and without mildly elevated testosterone alters small antral follicle morphology, numbers, health, and RNA transcriptome.

Authors:
Cecily V. Bishop, Ph.D., Fuhua Xu, Ph.D., Jing Xu, Ph.D., Alison Y. Ting, Ph.D., Etienne Galbreath, B.S., Whitney K. McGee, D.V.M., Ph.D., Mary B. Zelinski, Ph.D., Jon D. Hennebold, Ph.D., Judy L. Cameron, Ph.D., Richard L. Stouffer, Ph.D.

Volume 105, Issue 4, Pages 1023-1034

Abstract:

Objective:
To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consumption of a Western-style diet (WSD), with or without chronically elevated androgen levels since before puberty.

Design:
Cholesterol or T (n = 6 per group) implants were placed SC in female rhesus macaques beginning at 1 year of age (prepubertal), with addition of a WSD (high fat/fructose) at 5.5 years (menarche approximately 2.6 years). Ovaries were collected at 7 years of age. One ovary per female was embedded in paraffin for morphologic and immunohistochemical analyses. The SAFs (<2.5 mm) were dissected from the other ovary obtained at or near menses in a subgroup of females (n = 3 per group) and processed for microarray analyses of the SAF transcriptome. Ovaries of adult monkeys consuming a standard macaque diet (low in fats and sugars) were obtained at similar stages of the menstrual cycle and used as controls for all analyses. Setting:
Primate research center.

Animal(s):
Adult, female rhesus monkeys (Macaca mulatta).

Intervention(s):
None.

Main Outcome Measures:
Histologic analyses, SAF counts and morphology, protein localization and abundance in SAFs, transcriptome in SAFs (messenger RNAs [mRNAs]).

Result(s):
Compared with controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary, owing to the presence of more atretic follicles. Numbers of granulosa cells expressing cellular proliferation markers (pRb and pH3) was greater in healthy SAFs, whereas numbers of cells expressing the cell cycle inhibitor (p21) was higher in atretic SAFs. Intense CYP17A1 staining was observed in the theca cells of SAFs from WSD with or without T groups, compared with controls. Microarray analyses of the transcriptome in SAFs isolated from WSD and WSD plus T–treated females and controls consuming a standard diet identified 1,944 genes whose mRNA levels changed twofold or more among the three groups. Further analyses identified several gene pathways altered by WSD and/or WSD plus T associated with steroid, carbohydrate, and lipid metabolism, plus ovarian processes. Alterations in levels of several SAF mRNAs are similar to those observed in follicular cells from women with polycystic ovary syndrome.

Conclusion(s):
These data indicate that consumption of a WSD high in fats and sugars in the presence and absence of chronically elevated T alters the structure and function of SAFs within primate ovaries.

  • Amanda N. Kallen

    Thanks for a very interesting study – results are impressive and certainly suggest an effect of western style diet and elevated androgens on ovarian morphology. Have the authors done (or are planning to do) further study to see if a) this effect is ameliorated by metformin or anti-androgen therapy, and b) if dietary modification reverses the effects?

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