Mary B. Zelinski
The American Cancer Society estimated that 1 in 52 human females between birth and age 39 – that is, the pre-reproductive and reproductive years – are diagnosed with cancer per year. Currently, 1 in 250 people in the U.S. will be survivors of childhood cancer. Many patients will be treated with chemo- and/or radiation therapy. Premature ovarian failure and infertility are well-known side-effects of many cancer treatments. The ultimate goal of our work is to develop safe and effective methods for protecting female ovaries that contain follicles and their enclosed oocytes (eggs) from side-effect damage caused by anti-cancer therapies.With collaborators in Boston, we are testing agents administered directly to the ovary to see if they can protect follicles and oocytes from X-irradiation, and also whether normal offspring can be born after ovarian protection prior to ovarian X-irradiation in the mothers.With collaborators in the Oncofertility Consortium (http://oncofertility.northwestern.edu/) , we are growing monkey follicles in a bioengineered matrix that maintains the 3-dimensional architecture of the follicle, evaluating autotransplantation of ovarian cortex to readily accessible sites in primates, and optimizing cryopreservation methods for preserving ovarian tissue for subsequent transplantation or follicle culture. We will ultimately test whether each method will yield oocytes that can fertilize and lead to live offspring.
We developed a low dose treatment of a specific progesterone receptor modulator in female rhesus monkeys that permits normal ovarian and menstrual cycles, prevents pregnancy, and is reversible. These studies provided the basis for use of this female contraceptive in China. A Contraceptive Development Research Center was established in the Division of Reproductive & Developmental Sciences to further develop novel female contraceptives that act at specific sites in the ovary or reproductive tract. In the Nonhuman Primate Contraceptive Core, we conduct contraceptive and reversibility trials of the drugs developed in each project in the Contraceptive Center, we are testing agents that block receptor function to inhibit oocyte/embryo transport or fertilization within the oviduct thereby providing multiple novel approaches to female contraception.
KEY PUBLICATIONSTing AY, Yeoman RR, Lawson MS, Zelinski MB. In vitro development of secondary follicles from cryopreserved rhesus macaque ovarian tissue after slow-rate freeze or vitrification. Hum Reprod, 26:2461-2472, 2011. PMID: 21705370
Zelinski, MB, Murphy M, Lawson M, Pau F, Toscano N, Jacob D, Fanton J, Tilly JL. Intraovarian delivery of a spingosine-1 phosphate (S1O) agonist, FTY720, prior to ovarian X-irradiation yields fertilization, embryonic development and pregnancy in rhesus monkeys. Fertil Steril, 15:1440-1445.e1-7, 2011. Scientific Program Prize paper, 64th Annual Meeting of the American Society for Reproductive Medicine, 2008. PMID: 21316047
Xu J, Lawson MS, Yeoman RR, Zelinski MB, Stouffer RL. Secondary follicle growth and oocyte maturation during encapsulated three-dimensional culture in rhesus monkeys: effects of gonadotropins, oxygen, and fetuin. Hum Reprod, 26:1061-1072, 2011. PMID: 21362681Xu J, Bernuci MP, Lawson MS, Yeoman RR, Fisher TE, Zelinski MB, and Stouffer RL. Survival, growth, and maturation of secondary follicles from prepubertal, young and older adult, rhesus monkeys during encapsulated three-dimensional (3D) culture: effects of gonadotropins and insulin. Reproduction, 140:685-97, 2010. PMID: 20729335
Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK, Zelinski MB. Current achievements and future research directions in ovarian tissue culture, in bitro follicle development and transplantation: implications for fertility preservation. Hum Reprod, 16(4):395-414. PMID: 20124287
Peluffo M, Stouffer RL, Hennebold JD, Zelinski MB. Cumulus oocyte complexes from small antral follicles during the early follicular phase of spontaneous cycles in rhesus monkeys can expand and yield oocytes capable of maturation in vitro. Biol Reprod. 2010 Jun 2. [Epub ahead of print]. PMCID: PMC2957158
Shiying Jin S, Lei L, Shea LD, Zelinski MB, StoufferRL, Woodruff TK. Markers of growth and development in primate primordial follicles are preserved after slow cryopreservation. Fertil Steril, 93:2627-32, 2010.PMID: 20074723
Jensen JT, Vance J, Zelinski MB, Fanton JW, Stouffer RL. The phosphodiestrase inhibitor ORG 9935 inhibits oocyte maturation in the naturally-selected dominant follicle in rhesus monkeys. Contraception, 77:303-307, 2008. PMCID: PMC2505347
Lee DM, Yeoman RR, Battaglia DE, Stouffer RL, Zelinski-Wooten MB, Fanton JW, Wolf DP. Live birth after ovarian tissue transplant. Nature, 428:137-138, 2004. PMID: 15014485