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Reproductive Endocrinology and Science

Dr. Alan H. DeCherney, MD
  • Alan H. DeCherney, MD, Head, Section on Implantation and Oocyte Physiology
  • D. Randall Armant, PhD, Adjunct Scientist
  • Brian Kilburn, BS, Technician
  • Zhi-Bin Tong, MD, Staff Scientist

Deviations from the norm can prevent the establishment of pregnancy or contribute to obstetrical disorders associated with aberrant placentation. Through basic and translational research, our mission is to identify critical cellular and molecular events required for successful implantation and to understand their relationship to the pathologies of early pregnancy. Our objective is therefore to understand the biology of the developing blastocyst, which requires the differentiation of the trophectoderm—its outer epithelium—into invasive trophoblast cells and the maintenance of a cohort of pluripotent embryonic stem cells. We focus on the developing blastocyst, trophectoderm, and pluripotential embryonic stem cells and investigate the interactions between the uterine endometrium and implanting blastocyst at the inception of pregnancy. We are evaluating agents for cellular and molecular evidence of successful and pathologic implantation.

Regulation of blastocyst development

Armant, DeCherney; in collaboration with Brenner

Using in vitro approaches with both mouse and primate animal models, we investigated the role of the maternal environment on development of pre- and peri-implantation embryos. Previous work with mouse blastocysts revealed signaling pathways regulated by oxygen, growth factors, and the extracellular matrix; these pathways advance the trophoblast’s intrinsic developmental program. In the coming year, we plan to extend our studies of trophoblast differentiation and examine how the microenvironment sustains the pluripotent embryonic stem cell population within the blastocyst. Our collaborator Carol Brenner has established the rhesus monkey pre-implantation embryo model and works with several rhesus embryonic stem cell lines. Our upcoming studies will provide needed information on the comparative physiology of mouse and primate embryonic development and implantation.

Nuclear and cytoplasmic damage of pre-implantation embryos

Armant, DeCherney; in collaboration with Brenner

Fluorescent in situ hybridization analysis of blastomeres from pre-implantation embryos from young rhesus macaque females revealed a high chromosomal abnormality frequency that was surprisingly similar to rates demonstrated by in vitro–produced (IVP) human embryos. In the coming year, we plan to study monkey IVP embryos from older female animals and animals subjected to various ovulation-induction regimes. We are assessing mitochondrial replication and function to determine their impact on cytoplasmic cellular components, as the mitochondrion is central to energy and toxicity management. The proportion of mtDNA deletions in stimulated oocytes and embryos from rhesus macaques is significantly higher than that of mtDNA deletions in immature, unstimulated oocytes derived from ovaries of age-matched monkeys. These findings validate non-human primates as a model for investigating reproductive mechanisms relevant to human infertility. Our studies will have an impact on human in vitro fertilization where aneuploidy in embryos is common.

The evaluation of trophoblast differentiation and survival during human implantation is critical to the successful establishment of a pregnancy. We are studying multifunctional growth factors involved in normal trophoblast development and associated pathologies.

  • DeUgarte CM, Li M, Surrey M, Danzer H, Hill D, DeCherney AH. Accuracy of FISH analysis in predicting chromosomal status in patients undergoing preimplantation genetic diagnosis. Fertil Steril 2008;90:1049-1054.

Metabolomics of frozen/thawed immature human oocytes

Tong, DeCherney

Given that ATP is a principal donor of free energy and phosphate in many intracellular metabolic reactions and signal transduction pathways, we measured the ATP level in oocytes after a freezing/thawing process and compared the level to that in fresh oocytes (human oocytes from a stimulated IVF cycle that are discarded owing to their nuclear immaturity). ATP levels from surviving frozen/thawed oocytes are significantly lower than those in fresh oocytes. The low level results from cryopreservation, but, once the mitochondria begin to function after thawing, the ATP level rises to close to that of fresh oocyte. We are continuing our study to measure the ATP level in a larger number of oocytes and will extend our study by incubating post-thawed oocytes for either 2 or 3 hours to demonstrate the effect of the incubating time after thawing.

  • Manipalviratn S, DeCherney A. Clinical application of human oocyte cryopreservation. Rev Recent Clin Trials 2008;3:104-110.

Collaborators

  • Carol A. Brenner, PhD, Wayne State University School of Medicine, Detroit, MI
  • S.K. Dey, PhD, Vanderbilt Medical Center, Nashville, TN
  • Richard E. Leach, MD, Michigan State University, East Lansing, MI
  • Nita Mahile, PhD, Yale Medical Center, New Haven, CT
  • Roberto Romero, MD, Program in Perinatal Research and Obstetrics, NICHD, Detroit, MI
  • Susan M. Smith, PhD, University of Wisconsin, Madison, WI

For further information, contact decherna@mail.nih.gov.

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