Chronically elevated androgen and/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle

Cecily Bishop, Taylor E. Reiter, David Erikson, Carol Hanna, Brittany L. Daughtry, Shawn Chavez, Jon Hennebold, Richard Stouffer

Research output: Contribution to journalArticle

Abstract

Purpose: To investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n = 10/treatment) near the onset of menarche with implants containing either cholesterol (C) or testosterone (T, 4–5-fold increase above C) and a standard or “Western-style” diet alone (WSD) or in combination (T+WSD). Following ~ 3.5 years of treatment, females underwent controlled ovulation (COv, n = 7–10/treatment) cycles, and contents of the naturally selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas several degenerated oocytes were recovered in other groups (33–43% of T, WSD, and T+WSD samples). Levels of two chemokines and one growth factor were reduced (p < 0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p < 0.02). Changes in the expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.

Original languageEnglish (US)
JournalJournal of Assisted Reproduction and Genetics
DOIs
StatePublished - Jan 1 2019

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Granulosa Cells
Primates
Androgens
Oocytes
Diet
Follicular Fluid
RNA
Chemokines
Intercellular Signaling Peptides and Proteins
Menarche
Chromosome Mapping
Fibroblast Growth Factor 2
Periodicity
Metaphase
Ovulation
Macaca mulatta
Hydrocortisone
Testosterone
Steroids
Cholesterol

Keywords

  • Androgen
  • Follicular cytokines
  • Nonhuman primate
  • Oocyte quality
  • Periovulatory follicle
  • Western-style diet

ASJC Scopus subject areas

  • Reproductive Medicine
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Genetics(clinical)

Cite this

@article{5cf8d603680e4c64ab9d1eedacfb7264,
title = "Chronically elevated androgen and/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle",
abstract = "Purpose: To investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n = 10/treatment) near the onset of menarche with implants containing either cholesterol (C) or testosterone (T, 4–5-fold increase above C) and a standard or “Western-style” diet alone (WSD) or in combination (T+WSD). Following ~ 3.5 years of treatment, females underwent controlled ovulation (COv, n = 7–10/treatment) cycles, and contents of the naturally selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100{\%}) were retrieved in the C group, whereas several degenerated oocytes were recovered in other groups (33–43{\%} of T, WSD, and T+WSD samples). Levels of two chemokines and one growth factor were reduced (p < 0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p < 0.02). Changes in the expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.",
keywords = "Androgen, Follicular cytokines, Nonhuman primate, Oocyte quality, Periovulatory follicle, Western-style diet",
author = "Cecily Bishop and Reiter, {Taylor E.} and David Erikson and Carol Hanna and Daughtry, {Brittany L.} and Shawn Chavez and Jon Hennebold and Richard Stouffer",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s10815-019-01497-8",
language = "English (US)",
journal = "Journal of Assisted Reproduction and Genetics",
issn = "1058-0468",
publisher = "Springer New York",

}

TY - JOUR

T1 - Chronically elevated androgen and/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle

AU - Bishop, Cecily

AU - Reiter, Taylor E.

AU - Erikson, David

AU - Hanna, Carol

AU - Daughtry, Brittany L.

AU - Chavez, Shawn

AU - Hennebold, Jon

AU - Stouffer, Richard

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n = 10/treatment) near the onset of menarche with implants containing either cholesterol (C) or testosterone (T, 4–5-fold increase above C) and a standard or “Western-style” diet alone (WSD) or in combination (T+WSD). Following ~ 3.5 years of treatment, females underwent controlled ovulation (COv, n = 7–10/treatment) cycles, and contents of the naturally selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas several degenerated oocytes were recovered in other groups (33–43% of T, WSD, and T+WSD samples). Levels of two chemokines and one growth factor were reduced (p < 0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p < 0.02). Changes in the expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.

AB - Purpose: To investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n = 10/treatment) near the onset of menarche with implants containing either cholesterol (C) or testosterone (T, 4–5-fold increase above C) and a standard or “Western-style” diet alone (WSD) or in combination (T+WSD). Following ~ 3.5 years of treatment, females underwent controlled ovulation (COv, n = 7–10/treatment) cycles, and contents of the naturally selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas several degenerated oocytes were recovered in other groups (33–43% of T, WSD, and T+WSD samples). Levels of two chemokines and one growth factor were reduced (p < 0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p < 0.02). Changes in the expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.

KW - Androgen

KW - Follicular cytokines

KW - Nonhuman primate

KW - Oocyte quality

KW - Periovulatory follicle

KW - Western-style diet

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U2 - 10.1007/s10815-019-01497-8

DO - 10.1007/s10815-019-01497-8

M3 - Article

JO - Journal of Assisted Reproduction and Genetics

JF - Journal of Assisted Reproduction and Genetics

SN - 1058-0468

ER -