Endocrine disrupting compounds (EDCs) are ubiquitous, they threaten the reproduction and health of adults, yet the field fails to grasp their exact risks and mechanisms of action. Normal oocyte development is at the root of embryogenesis, development to term, and even the health of the resulting adult into late in life. There is thus a clear impetus to ensure the quality of oocytes, particularly in face of a large lis of chemical insults in our environment. Once risks, effects, and mechanisms are identified, we will then be in a position to eliminate the insult as well as manage, and even prevent, infertility and certain adult diseases. A complex, dynamic, and vulnerable follicular microenvironment permits the development of a good quality oocyte. It is thus essential to begin addressing the influences of EDCs, including bisphenol-A (BPA), on the function and development of not only the oocyte itself but also each cellular compartment making up the antral follicle. There are numerous experimental limitations to investigations thus far, among which is the fact that an animal model in which the specifics of folliculogenesis and oogenesis recapitulate most closely those occurring in human has not been employed. The bovine model fills in such gap, along with providing many other experimental advantages. With a focus on the bovine oocyte and antral follicle, this research program is particularly well suited to resolve the existing challengs in the field. The proposed experiments will: 1) measure systemic (in serum and urine) and intrafollicular (in follicular fluid) levels of EDCs in three groups of cows (abattoir animals, a conventional dairy herd, and an organic dairy herd);and 2) determine the effects of BPA on the development and function of bovine oocytes, granulosa cells, and theca cells derived from antral follicles. The assessment of cellular differentiation state and function will include meioti progression and chromosomal segregation (for oocytes), cell proliferation and cell death (for granulosa and theca cells), production of steroids and other essential secreted factors (for granulosa and theca cells), redox and pro-/anti-oxidant states (for all cell types), and ability to support early embryonic development (for oocytes). Such comprehensive assessment of EDCs in the follicular milieu and BPA effects on the antral follicle will provide essential knowledge fo future studies and in the long-term, for the protection of human reproductive and adult health.

Public Health Relevance

Using a clinically relevant animal model, this proposal aims to determine the effects of endocrine disrupting compounds on the oocyte and the ovarian follicle, which is the complex and specialized structure that nurtures the developing oocyte. With the health of adults, neonates, fetuses, and embryos all depending upon normal development of the oocytes from which they arise, findings will help ensure that humans can rely on oocytes of optimal quality, thereby providing critical foundations for the improvement of not only female reproductive but also adult health.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Academic Research Enhancement Awards (AREA) (R15)
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Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
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Heindel, Jerrold
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Middlebury College
Schools of Arts and Sciences
United States
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Campen, Kelly A; Kucharczyk, Katherine M; Bogin, Benjamin et al. (2018) Spindle abnormalities and chromosome misalignment in bovine oocytes after exposure to low doses of bisphenol A or bisphenol S. Hum Reprod 33:895-904
Campen, K A; Lavallee, M; Combelles, Cmh (2018) The impact of bisphenol S on bovine granulosa and theca cells. Reprod Domest Anim 53:450-457