Kelly E. Mayo Gene regulation in the mammalian neuroendocrine system

Research Interests

Our research program investigates hormone action and signal transduction in the mammalian reproductive system. We focus on the ovary, and our recent work studies cellular communication through the Notch pathway and its integration with hormonal signaling. The ovary is central to female reproduction, secreting critical hormones and serving to nurture the female germ cell, the oocyte, through ovulation. Ovarian follicles serve as a critical niche for supporting the growth and maturation of the oocyte, and bidirectional signaling between the oocyte and surrounding somatic granulosa cells is crucial to the establishment and function of this niche.

Multiple Notch ligands and receptors are expressed in the developing and adult mouse ovary, and use of a transgenic Notch reporter line has revealed spatially, temporally, and hormonally regulated Notch pathway activity. Using both pharmacologic inhibition of Notch signaling and conditional knockout of genes for the receptor Notch2 or the ligand Jagged1, we demonstrated functional roles for Notch signaling in the formation and growth of ovarian follicles, and in female fertility. Based on the finding that pituitary gonadotropins regulate Notch signaling in mature preovulatory ovarian follicles, we used siRNA knockdown of the ligand Jag1 or the canonical Notch transcriptional regulator Rbpj in cultured granulosa cells to reveal a suppression of steroid hormone secretion (estradiol and progesterone) and an enhanced rate of proliferation, indicating that Notch modulates the balance between proliferation and differentiation in granulosa cells of mature follicles. Other aspects of our work explore relationships between Notch and Inhibin/Activin signaling in granulosa cells of growing ovarian follicles.

Our research focuses on molecular mechanisms regulating normal reproductive function, but is substantially informed by, and relevant to, reproductive disorders that impact fertility or result in infertility. Given the many conserved features of follicle function and ovarian regulation across mammalian species, these studies in mice are expected to have direct applicability to human reproductive health and disease.

Selected Publications

Regulation of Follicle Formation and Development by Ovarian Signaling Pathways. Prasasya RD and Mayo KE (2019). In The Ovary (eds. P. Leung and E. Adashi) 3rd edition. Elsevier (Academic Press): 23-42.

Notch Signaling Regulates Differentiation and Steroidogenesis in Female Mouse Ovarian Granulosa Cells. Prasasya RD and Mayo KE. Endocrinology. 2018 January 1;159(1):184-198.

The role of Notch signaling in the mammalian ovary. Vanorny DA and Mayo KE. Reproduction. 2017 June 1;153(6):R187-R204.

Gonadotropin Signaling in the Ovary. Hunzicker-Dunn M and Mayo KE. In Knobil and Neill's Physiology of Reproduction (eds. T. Plant and A. Zeleznik) 4th edition. Academic Press, Waltham, MA, 2015:895-945.

Notch Signaling Regulates Ovarian Follicle Formation and Coordinates Follicular Growth.  Vanorny DA, Prasasya RD, Chalpe AJ, Kilen SM, and Mayo KE. Molecular Endocrinology. 2014 April 1;28(4):499-511.

View all publications by Kelly E. Mayo listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.