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Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The main goals of this study were to investigate the expression of anti-Müllerian hormone (AMH) and its receptor (AMHR2) during follicular development in primates, and to evaluate the potential of AMH as a biomarker for follicle growth and oocyte maturation in vitro.

Methods

The mRNA and protein expression of AMH and AMHR2 were determined using isolated follicles and ovarian sections from rhesus macaques (n = 4) by real-time PCR and immunohistochemistry, respectively. Isolated secondary follicles were cultured individually. Follicle growth and media AMH concentrations were assessed by ELISA. The mRNA expression profiles, obtained from RNA sequencing, of in vitro- and in vivo-developed antral follicles were compared. Secondary follicles from additional animals (n = 35) were cultured. Follicle growth, oocyte maturation, and media AMH concentrations were evaluated for forecasting follicular development in vitro by AMH levels.

Results

AMH immunostaining was heterogeneous in the population of preantral follicles that were also stained for AMHR2. The mRNA expression profiles were comparable between in vivo- and in vitro-developed follicles. AMH levels produced by growing follicles were higher than those of nongrowing follicles in culture. With a cutoff value of 1.40 ng/ml, 85 % of nongrowing follicles could be identified while eliminating only 5 % of growing follicles. Growing follicles that generated metaphase II-stage oocytes secreted greater amounts of AMH than did those yielding immature germinal vesicle-stage oocytes.

Conclusions

AMH, co-expressed with AMHR2, was produced heterogeneously by preantral follicles in macaques with levels correlated positively with follicle growth and oocyte maturation. AMH may serve as a biomarker for primate follicular development in vitro.

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Acknowledgments

We are thankful for the assistance provided by members of the Division of Comparative Medicine, the Endocrine Technology Support Core, the Histopathology-Morphology Research Core, the Assisted Reproductive Technologies Support Core, the Molecular & Cellular Biology Support Core, and the Biostatistics and Bioinformatics Unit at ONPRC, as well as the OHSU Massively Parallel Sequencing Shared Resource. The valuable assistance of Ms. Maralee Lawson at ONPRC with follicle culture is appreciated. We are grateful to Dr. Richard L. Stouffer at ONPRC for his valuable expertise and critical review of the manuscript.

Research reported in this publication was supported by the National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01HD082208, NIH Office of Research on Women’s Health/NICHD K12HD043488 (Building Interdisciplinary Research Careers in Women’s Health, BIRCWH), NIH Office of the Director P51OD011092 ONPRC Pilot Grant, Collins Medical Trust, American Society for Reproductive Medicine, and Medical Research Foundation of Oregon. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Jing Xu & Fuhua Xu

  2. Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Jing Xu

  3. Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    John H. Letaw & Betsy M. Ferguson

  4. OHSU-PSU School of Public Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Byung S. Park

  5. Integrated Genomics Laboratory, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Robert P. Searles

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  1. Jing Xu
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Corresponding author

Correspondence to Jing Xu.

Ethics declarations

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This study was funded by the National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01HD082208, NIH Office of Research on Women’s Health/NICHD K12HD043488 (Building Interdisciplinary Research Careers in Women’s Health, BIRCWH), NIH Office of the Director P51OD011092 ONPRC Pilot Grant, Collins Medical Trust, American Society for Reproductive Medicine, and Medical Research Foundation of Oregon.

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Capsule

AMH, co-expressed with AMHR2, was produced heterogeneously by preantral follicles in macaques with levels correlated positively with follicle growth and oocyte maturation. AMH may serve as a biomarker for primate follicular development in vitro.

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Xu, J., Xu, F., Letaw, J.H. et al. Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro. J Assist Reprod Genet 33, 1665–1675 (2016). https://doi.org/10.1007/s10815-016-0804-3

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  • DOI: https://doi.org/10.1007/s10815-016-0804-3

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