Molecular Recognition in Biological Systems and Bioinformatics

• Ovarian reproductive aging
• Biomarkers of chemotherapy induced ovarian damage
• Healthcare issues in maternal health
  Infertility

Our recent laboratory work has demonstrated that cisplatin, a commonly used chemotherapeutic agent causes ovarian damage by affecting the function of small growing follicles. Furthermore, the damage caused to the ovarian follicles can be monitored using serum biomarkers such as MIS and stimulated inhibin A and inhibin B. We have recently demonstrated that the FDA approved drug, mesna, currently used in the clinical setting to reduce systemic side effects of various chemotherapeutics, will reduce the cytotoxic effects of cisplatin on the ovary.

In addition to investigating the effects of chemotherapy on the ovary, we have investigated the use of different serum biomarkers to monitor ovarian reserve and identify biomarkers that are more accurate and earlier indicators of ovarian reserve than those currently used in clinical practice. Our recent work supports the use of MIS and stimulated inhibin A and inhibin B to monitor ovarian reserve as both appear to be more accurate and better early indicators of ovarian decline in reproductive aging.

Our laboratory was the first to discover the presence of HCN channels in the ovary. We identified their decline throughout the reproductive aging process and we are also investigating the effects of cisplatin administration on HCN channel distribution in the ovary.

We are also investigating the presence of ion channels in GnRH neurons and whether or not they may play a role in the rhythmic bursting of GnRH. We have recently identified the presence of HCN channels in the GnRH neuron from both the rat brain and from GT1-7 cells. Further studies are determining the presence or absence of other ion channels.

Rat, mouse

MIS, HCN, inhibin A, inhibin B, FSH, progesterone, caspases, NFkB signaling pathway, GnRH, Kv family

Infertility, reproductive medicine, chemotherapy

Western blot, ELISA, immunohistochemistry, TUNEL, RT-PCR, whole animal studies, cell culture

GT1-7 cells, human luteinized granulosa cells

Premature ovarian failure, chemotherapy induced ovarian damage, ovarian aging, ovary, channel expression in the ovary leading to decreased ovarian function, ion channel expression in GnRH neurons

Yeh J, Kim BS, Gaines L, Peresie J, Page C, Arroyo A. The expression of hyperpolarization activated cyclic nucleotide gated (HCN) channels in the rat ovary are dependent on the type of cell and the reproductive age of the animal: a laboratory investigation. Reprod Biol Endocrinol. 2008;6:35.

Yeh J, Kim BS, Peresie J. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. Am J Obstet Gynecol. 2008 Apr;198(4):463 e1-7.

Yeh J, Kim BS, Liang YJ, Peresie J. Baseline and stimulated serum inhibin levels as biomarkers of cisplatin-induced ovarian damage in female rats. Am J Obstet Gynecol. 2008 Jan;198(1):82 e1-6.

Yeh J, Kim BS. Increasing blunting of inhibin responses to dynamic ovarian challenge is associated with reproductive aging in the rat. Reproductive Sciences. 2007;14(1):10-9.

Yeh J, Kim BS, Peresie J, Liang YJ, Arroyo A. Serum and ovarian Müllerian inhibiting substance, and their decline in reproductive aging. Fertil Steril. 2007;87(5):1227-30.

Arroyo A, Kim B, Rasmusson RL, Bett G, Yeh J. Hyperpolarization-activated cation channels are expressed in rat hypothalamic gonadotropin-releasing hormone (GnRH) neurons and immortalized GnRH neurons. J Soc Gynecol Investig. 2006;13(6):442-50.

Yeh J, Kim B, Liang YJ, Peresie J. Müllerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage. Biochem Biophys Res Commun. 2006 September;348(2):337-44

Yeh J, Wactawski-Wende J, Shelton JA, Reschke J. Temporal trends in the rates of trial of labor in low-risk pregnancies and their impact on the rates and success of vaginal birth after cesarean (VBAC). Am J Obstet Gynecol. 2006 January;194(1):144-52.

Yeh J, Shelton JA. Increasing prepregnancy body mass index: analysis of trends and contributing variables. Am J Obstet Gynecol. 2005;193:1994-8.

Arroyo A, Yeh J. Understanding the menopausal transition, and managing its clinical challenges. Sex Reprod Menopause. 2005;3(1):12-17.