Investigator Program in Membrane Biology, Mass General Research Institute

Professor of Medicine, Emerita Emeritus, Harvard Medical School

Richard Moerschner Endowed MGH Research Institute Chair in Men’s Health Massachusetts General Hospital

Charles and Ann Sanders MGH Research Scholar Massachusetts General Hospital

aquaporins; basal cell function; epididymis; epithelial cells; luminal acidification; luminal fluid; male reproductive physiology; proton-translocating atpases; pseudostratified epithelia; sperm concentration; sperm maturation; sperm storage; spermatozoa; vacuolar proton-translocating atpases; vas deferens

Our laboratory examines physiological and pathophysiological processes involved in the regulation of male fertility. In the United States, millions of couples are infertile. A significant number of these couples are affected by male fertility defects that are still unexplained.

A major cause of male infertility is the production of sperm that have reduced function, including low motility and poor interaction with oocytes. Spermatozoa acquire their ability to become motile and to fertilize an egg in the lumen of the tubules that form the epididymis, an organ that is located downstream of the testis.

Thus, the study of epididymal function might provide clues to understand better the causes of some unexplained cases of male infertility.

One critical feature of the epididymal luminal fluid is that it is maintained acidic (9). Acidic pH and low bicarbonate concentration are involved in maintaining sperm in an immotile, dormant state during their storage period in the epididymis. Thus, a defect in the acidification capacity of the epididymis might have important consequences for male reproductive physiology. A second major role of the epididymis is related to its concentrating capacity (2). Significant fluid reabsorption occurs in this organ, which results in a marked increase in spermatozoa concentration.

Our research is divided into four major themes:

a) luminal acidification and its regulation;

b) modeling of basal cell function in pseudostratified epithelia;

c) fluid and solute transport; and

d) interaction between the various cell types that are present in the epithelium, and that work in a concerted manner to establish and maintain the appropriate environment for sperm maturation, storage and concentration in the epididymis.

These four NIH-funded studies focus on the intact organ.

By using a multidisciplinary approach including high-resolution laser scanning confocal microscopy and intravital multiphoton microscopy, 3D reconstructions of single cells, and luminal perfusion of the epididymis in vivo, we are studying the function of epithelial cells while they reside in their native environment.