Zelieann R Craig
Assistant Professor, BIO5 Institute
Assistant Professor, Physiological Sciences - GIDP
Associate Professor, Animal and Comparative Biomedical Sciences
Primary Department
Department Affiliations
(520) 621-9965
Work Summary
We investigate how the chemicals in our daily lives interact with the female reproductive system and influence fertility. We hope that our discoveries will help reduce the incidence of infertility and improve women's health.
Research Interest
Nearly 50 million couples experience some form of infertility worldwide. Several factors increase a woman’s risk for infertility including aging, stress, and exposure to chemicals. A group of chemicals collectively known as phthalates have been classified as endocrine disruptors based on their ability to interact with the reproductive system. Phthalates have been detected in human urine, animal tissues, and feed. Despite these observations, how phthalates interact with the female reproductive system and what this means for overall fertility is currently unknown. Dr. Craig's work focuses on understanding how phthalates affect the function of the ovary, the major reproductive organ in females. Thus, work in her laboratory is focused on using animal models to help us understand the mechanisms by which phthalates exert their effects on the ovary, determine whether phthalates cause female infertility, and examine whether the effects of phthalates on female reproduction can be prevented or reversed. Using this knowledge she hopes to inspire and guide future work aimed at reducing, preventing, and/or reversing chemical-related infertility in humans and animals. Keywords: Infertility, Toxicology, Endocrine Disruptors, Phthalates, Reproduction

Publications

Barton, J. K., Connolly, D. C., Craig, Z. R., Chambers, S. K., Hutchens, G. V., Dominguez Cooks, J. P., Koevary, J. W., Howard, C. C., Rice, P. F., & Hoyer, P. (2018). Comparison of Markers of Reproductive Function in Female C57Bl/6 versus TgMISIIR-TAg Transgenic Mice: Effect of VCD exposure on Ovarian Failure.. Comparative Medicine.
BIO5 Collaborators
Jennifer Kehlet Barton, Zelieann R Craig
Craig, Z. R., Davis, J. R., Marion, S. L., Barton, J. K., & Hoyer, P. B. (2010). 7,12-Dimethylbenz[A]Anthracene Induces Sertoli-Leydig-Cell Tumors in the Follicle-Depleted Ovaries of Mice Treated with 4-Vinylcyclohexene Diepoxide. COMPARATIVE MEDICINE, 60(1), 10-17.
BIO5 Collaborators
Jennifer Kehlet Barton, Zelieann R Craig
Rivera, Z., Christian, P. J., Marion, S. L., Brooks, H. L., & Hoyer, P. B. (2009). Steroidogenic capacity of residual ovarian tissue in 4-vinylcyclohexene diepoxide-treated mice. Biology of reproduction, 80(2), 328-36.
BIO5 Collaborators
Heddwen L Brooks, Zelieann R Craig

Menopause is an important public health issue because of its association with a number of disorders. Androgens produced by residual ovarian tissue after menopause could impact the development of these disorders. It has been unclear, however, whether the postmenopausal ovary retains steroidogenic capacity. Thus, an ovary-intact mouse model for menopause that uses the occupational chemical 4-vinylcyclohexene diepoxide (VCD) was used to characterize the expression of steroidogenic genes in residual ovarian tissue of follicle-depleted mice. Female B6C3F1 mice (age, 28 days) were dosed daily for 20 days with either vehicle or VCD (160 mg kg(-1) day(-1)) to induce ovarian failure. Ovaries were collected on Day 181 and analyzed for mRNA and protein. Acyclic aged mice were used as controls for natural ovarian senescence. Relative to cycling controls, expression of mRNA encoding steroidogenic acute regulatory protein (Star); cholesterol side-chain cleavage (Cyp11a1); 3beta-hydroxysteroid dehydrogenase (Hsd3b); 17alpha-hydroxylase (Cyp17a1); scavenger receptor class B, type 1 (Scarb1); low-density lipoprotein receptor (Ldlr); and luteinizing hormone receptor (Lhcgr) was enriched in VCD-treated ovaries. In acyclic aged ovaries, mRNA expression for only Cyp17a1 and Lhcgr was greater than that in controls. Compared to cycling controls, ovaries from VCD-treated and aged mice had similar levels of HSD3B, CYP17A1, and LHCGR protein. The pattern of protein immunofluorescence staining for HSD3B in follicle-depleted (VCD-treated) ovaries was homogeneous, whereas that for CYP17A1 was only seen in residual interstitial cells. Circulating levels of FSH and LH were increased, and androstenedione levels were detectable following follicle depletion in VCD-treated mice. These findings support the idea that residual ovarian tissue in VCD-treated mice retains androgenic capacity.

Craig, Z. R., Curran, M. A., Barnett, M. A., Pollitt, A. M., & Helm, S. V. (2017). RC1: Differentiating environmental concern in the context of psychological adaption to climate change. Global Environmental Change. doi:https://doi.org/10.1016/j.gloenvcha.2017.11.012
Craig, Z. R., Singh, J., Gupta, R. K., & Flaws, J. A. (2014). Co-treatment of mouse antral follicles with 17β-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression. Reproductive toxicology (Elmsford, N.Y.), 45, 45-51.

Mono-2-ethyhexyl phthalate (MEHP) is a metabolite of a plasticizer found in many consumer products. MEHP inhibits mouse ovarian follicle growth by reducing 17β-estradiol (E2) production. Yet, whether MEHP causes follicle death (atresia) is unclear. We hypothesized that MEHP causes atresia by altering apoptosis gene expression, and that E2 co-treatment blocks these effects. Follicles were exposed to MEHP (0.36-36μM)±E2 for 48-96h to determine the effect of MEHP±E2 on atresia and gene expression. MEHP increased atresia, but this effect was blocked by co-treatment with E2. MEHP increased the expression of the pro-apoptotic gene Aifm1, but decreased that of the pro-apoptotic gene Bok and the anti-apoptotic gene Bcl2l10. E2 interfered with MEHP-induced changes in Aifm1 and Bcl2l10. Our findings suggest that decreased E2 levels are required for MEHP-induced follicle atresia and that Aifm1, Bok, and Bcl2l10 are involved in this process.