Das Debabrata, Arur Swathi

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.| Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Mol Reprod Dev. 2017 Jun;84(6):444-459. doi: 10.1002/mrd.22806. Epub 2017 Apr 24.

Insulin signaling regulates various aspects of physiology, such as glucose homeostasis and aging, and is a key determinant of female reproduction in metazoans. That insulin signaling is crucial for female reproductive health is clear from clinical data linking hyperinsulinemic and hypoinsulinemic condition with certain types of ovarian dysfunction, such as altered steroidogenesis, polycystic ovary syndrome, and infertility. Thus, understanding the signaling mechanisms that underlie the control of insulin-mediated ovarian development is important for the accurate diagnosis of and intervention for female infertility. Studies of invertebrate and vertebrate model systems have revealed the molecular determinants that transduce insulin signaling as well as which biological processes are regulated by the insulin-signaling pathway. The molecular determinants of the insulin-signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to mammals-yet, physiological differences in signaling still exist. Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates. In contrast, insulin signaling in Drosophila and Caenorhabditis elegans directly regulates oocyte growth and maturation. In this review, we compare and contrast insulin-mediated regulation of ovarian functions in mammals, lower vertebrates, C. elegans, and Drosophila, and highlight conserved signaling pathways and regulatory mechanisms in general while illustrating insulin's unique role in specific reproductive processes.

Lan Chen-Wei, Chen Mei-Jou, Tai Kang-Yu, Yu Danny Cw, Yang Yu-Chieh, Jan Pey-Shynan, Yang Yu-Shih, Chen Hsin-Fu, Ho Hong-Nerng

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Genome and Systems Biology Degree Program, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan university Taipei, Taiwan.| Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan university Taipei, Taiwan.

Sci Rep. 2015 Oct 13;5:14994. doi: 10.1038/srep14994.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Although its aetiology and pathogenesis remain unclear, recent studies suggest that the dysfunction of granulosa cells may partly be responsible. This study aimed to use cDNA microarray technology to compare granulosa cell gene expression profiles in women with and without PCOS to identify genes that may be aetiologically implicated in the pathogenesis of PCOS. The study cohort included 12 women undergoing in vitro fertilization, six with PCOS and six without PCOS. Differential gene expression profiles were classified by post-analyses of microarray data, followed by western blot analyses to confirm the microarray data of selected genes. In total, 243 genes were differentially expressed (125 upregulated and 118 downregulated) between the PCOS and non-PCOS granulosa cells. These genes are involved in reproductive system development, amino acid metabolism and cellular development and proliferation. Comparative analysis revealed genes involved in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) signaling pathways. Western blot analyses confirmed that mitogen-activated protein kinase kinase kinase 4 and phospho-ERK1/2 were decreased in PCOS granulosa cells. This study identified candidate genes involved in MAPK/ERK signaling pathways that may influence the function of granulosa cells in PCOS.