Vol 10, Issue 11, 2017 Online - 2455-3891 Print - 0974-2441 NEW INSIGHTS OF MAMMARY GLAND DURING DIFFERENT STAGES OF DEVELOPMENT MANOJ KUMAR JENA 1 , ASHOK KUMAR MOHANTY 2 * 1 Department of Biotechnology, Lovely Professional University, Phagwara - 144 411, Punjab, India. 2 Animal Biotechnology Centre, National Dairy Research Institute, Karnal - 132 001, Haryana, India. Email: ashokmohanty1@gmail.com Received: 17 June 2017, Revised and Accepted: 20 July 2017 ABSTRACT Mammary gland is a unique organ with its function of milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells proliferate, differentiate, undergo apoptosis, and tissue remodeling following a cyclic pathway in lactation – involution – lactation cycle, thus fine tuning the molecular events through hormones, and regulatory molecules. Several studies are performed on the mammary gland development, lactogenesis, and involution process in molecular details. The developmental stages of mammary gland are embryonic, pre- pubertal, pubertal, pregnancy, lactation, and involution. Major developmental processes occur after puberty with hormones and growth factors playing crucial role. The two major pathways such as Janus kinases-signal transducer and activator of transcription pathway and PI3K-Akt pathway play a major role in maintaining the lactation. The involution process is a well-orchestrated event involving several signaling molecules and making the gland ready for subsequent lactation. The review focuses on findings with molecular details of different stages of the mammary gland development and signaling pathways involved in lactation–involution cycle. Deep insight into the developmental stages of mammary gland will pave the way to understand mammary gland biology, apoptosis, oncogenesis, and it will help the researchers to use mammary gland as a model for research on various aspects. Keywords: Mammary gland, Lactation, Involution, Apoptosis, Development. INTRODUCTION Mammary gland (modified sebaceous gland) is exocrine in nature and made up of branched network of ducts ending in alveoli [1]. This gland is an excellent system to study the molecular events occurring in proliferation and differentiation of cells as well as cancer cell development (oncogenesis) [2]. This organ is unique in the sense; it can involute and regain its shape in each pregnancy-lactation-involution cycle. Mammary gland development mainly occurs after birth regulated by peptide and steroid hormones [3]. A complex cross-talk exists among various proteins expressed in different stages (pregnancy, lactation, and involution) during the functional mammary gland development. Intensive efforts have been made to unravel the molecular mechanisms involved in lactogenesis, apoptosis of mammary epithelial cells (MECs), and organ remodeling [1,4-7]. A number of previous studies at transcriptome level have been performed on this aspect. For example, cDNA library prepared from pooled sample of bovine mammary tissues - with a number of ESTs, paved the way for functional genomics studies of mammary gland [8]. Similarly, DNA microarray study comparing gene expression profiles of lactating and non-lactating bovine mammary tissue revealed many novel and interesting differentially expressed genes such as cell cycle regulators, mediators of apoptosis, and oncogenes [9]. Microarray analysis of transcriptional changes during pregnancy cycle of mouse mammary gland with a focus on lactation–involution transition revealed putative roles of death receptors and immune mediators in post-lactational regression [10]. Involution is associated with an immune cascade and acute phase response genes such as LBP, CD14, and signal transducer and activator of transcription (STAT)3 [11]. The CCAAT/enhancer binding protein delta is a crucial regulator of pro-apoptotic gene expression positioned with STAT3 at upstream and several pro- and anti-apoptotic genes at downstream level. A number of differentially expressed genes were identified by microarray analysis to understand the molecular events during the transition from late pregnancy to lactation in the mammary gland of Holstein cows [12]. It is observed that milk composition varies with stage of lactation which is specific to each species [13]. Milk is rich source of bioactive peptides (derived from milk proteins) which have antioxidant and antibacterial property [14]. Thus, it is important to understand the molecular events occurring during lactation which will help to unravel more about the milk components. This review focuses on the molecular details of mammary gland development with latest findings on changes in the mammary gland during pregnancy and lactation. This will help the researchers to understand mammary gland biology and use this organ as a model for different research area. FUNCTIONAL ANATOMY OF MAMMARY GLAND Mammary gland is a cutaneous gland such as sebaceous and sweat glands, producing milk to feed the young offspring in female. Histologically, it is a compound tubuloalveolar gland in the advanced mammals originating from the ectoderm and evolved from apocrine glands [15,16]. Bovine mammary gland is composed of two halves separated by the median suspensory ligament which primarily supports the udder along with the lateral suspensory ligament. Blood supply is mainly through the external pudendal artery, and venous drainage through the venous circle located at the base of the abdominal wall [16]. Mammary gland is made up of a branching network of ducts that end in alveoli. Alveoli are the basic functional units of the milking mammary gland and are grouped as lobules which connect to the collecting duct system. Mammary gland is a complex secretory organ with number of cell types: Epithelial cells (form the ductal network); adipocytes (constitute the fat pad); vascular endothelial cells (form blood vessels); stromal cells, including fibroblasts; and different immune cells [17]. The epithelial cells are of two types: Luminal and basal. Luminal epithelia form alveoli and duct system, whereas the basal one form myoepithelial cells involved in milk ejection. DEVELOPMENT OF MAMMARY GLAND Hormones play significant role in mammary gland development through distinct stages (Fig. 1). The mammary gland mainly consists of fat and connective tissue before puberty, and there is moderate elongation of epithelia into the fat pad which is not hormone-dependent. Ovarian steroid hormones stimulate the extension, and branching of ducts after © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2017.v10i11.20801. Review Article