The developmental origins of adult disease hypothesis has gained strength as a powerful explanation for risk of some of the most prevalent and morbid human conditions. According to this theory, risk of disease in adulthood is initially induced by fetal responses to maternal conditions and exposures. Central to the developmental origins hypothesis is the concept of developmental plasticity which involves altered gene expression as a result of non-genomic modifications to DNA. Growing evidence supports the concept that developmental programming may occur from a window that spans periconception through postnatal life. Epidemiologic data supporting a relationship between assisted reproductive technologies, low birth-weight and rare conditions involving imprinted genes makes it plausible that additional exposures around the time of conception may also impact fetal growth. The full impact of impaired fetal growth may not be completely evident until years after birth when later developmental and reproductive milestones can be affected. We hypothesize that specific maternal exposures around the time of conception and in utero are associated with neonatal markers of metabolism, development and ovarian function. This study will measure several maternal exposures around conception and in utero that may impact developmental plasticity and post natal disease risk. Maternal levels of folate, vitamin B12, Vitamin D and the endocrine disrupting chemical Bisphenol-A will be measured. Cohorts of fertile women, infertile women seeking treatment will be recruited for study. At birth, neonatal weight and placental dimensions will be measured. Samples of cord blood from neonates will also be collected to measure biomarkers of metabolism (leptin, 1GF1, IFG2, Insulin, IGFBP3) and ovarian function (Anti-Mullerian Hormone). Results from this pilot study should help us design an appropriately powered clinical trial with the potential for the Reproductive Medicien Network to undertake.

Public Health Relevance

It is anticipated that results from the proposed pilot project could lead to larger scale investigations that would explore the impact of maternal exposures on developmental and reproductive outcomes in mechanistic detail. Such studies could make significant impact on clinical practice as and education of women attempting pregnancy in ways that could optimize fetal outcomes and minimize disease risk in adults.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD068157-03
Application #
8446935
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$121,067
Indirect Cost
$45,401
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hur, Stella K; Freschi, Andrea; Ideraabdullah, Folami et al. (2016) Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes. Proc Natl Acad Sci U S A 113:10938-43
Meyer-Ficca, Mirella L; Ihara, Motomasa; Bader, Jessica J et al. (2015) Spermatid head elongation with normal nuclear shaping requires ADP-ribosyltransferase PARP11 (ARTD11) in mice. Biol Reprod 92:80
Bryant, Jessica M; Donahue, Greg; Wang, Xiaoshi et al. (2015) Characterization of BRD4 during mammalian postmeiotic sperm development. Mol Cell Biol 35:1433-48
Hu, Jialei; Donahue, Greg; Dorsey, Jean et al. (2015) H4K44 Acetylation Facilitates Chromatin Accessibility during Meiosis. Cell Rep 13:1772-80
Butts, Samantha F; Guidotti, Tee L (2014) What are some potential reproductive hazards in the hospital environment? J Occup Environ Med 56:e163-5
Ihara, Motomasa; Meyer-Ficca, Mirella L; Leu, N Adrian et al. (2014) Paternal poly (ADP-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression. PLoS Genet 10:e1004317
Mainigi, Monica A; Olalere, Devvora; Burd, Irina et al. (2014) Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod 90:26
Butts, Samantha F; Owen, Carter; Mainigi, Monica et al. (2014) Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011. Fertil Steril 102:1041-1047.e1
Butts, Samantha F; Ratcliffe, Sarah; Dokras, Anuja et al. (2013) Diagnosis and treatment of diminished ovarian reserve in assisted reproductive technology cycles of women up to age 40 years: the role of insurance mandates. Fertil Steril 99:382-8
Butts, Samantha F; Guo, Wensheng; Cary, Mark S et al. (2013) Predicting the decline in human chorionic gonadotropin in a resolving pregnancy of unknown location. Obstet Gynecol 122:337-43

Showing the most recent 10 out of 17 publications