FEMALE REPRODUCTIVE TRACT - B
Wednesday, August 4, 2004
10:30 AM–12:30 PM
(805) UTERINE AND OVIDUCT EXPRESSION OF CUBILIN, MEGALIN, APOLIPOPROTEIN J AND APOLIPOPROTEIN AI.
Argraves, Scott1, Morales, Carlos2, 1 Medical University of South Carolina, Charleston, SC2 McGill Univeristy, Montreal, Canada
ABSTRACT- Sperm maturation and capacitation involve the remodeling of the plasma membrane. Capacitation occurs during the transit of the spermatozoon in the uterus and oviduct. Luminal proteins secreted by the epithelial cells lining the male and female reproductive tracts largely mediate these processes and a selective reduction and a rearrangement of cholesterol in various domains of the sperm plasma membrane occur in these organs. Capacitation, is essential in establishing acrosomal responsiveness and fertilizing capacity. Candidate proteins for lipid exchange to and from the sperm membrane includes apolipoprotein J (apoJ) and apoA-I, two soluble lipid-binding proteins associated with high-density lipoproteins (HDL) in human plasma. Both proteins have been shown to bind to the sperm plasma membrane and apoJ is thought to retrieve lipids from the sperm membrane and to be taken up into the endocytic apparatus of epithelial cells lining the male reproductive tract. ApoJ uptake is mediated by the low-density lipoprotein receptor-related protein-2 (LRP-2/megalin), and this process may be one of multiple modifications of the sperm membrane that occurs during sperm maturation in the epididymis. Cubilin, a membrane-associated epithelial receptor, co-localizes with megalin in various absorptive epithelia, including the epididymis. While both mediate the endocytosis of various ligands, cubilin requires the endocytic activity of megalin for its own internalization. The objectives of this investigation were to localize megalin and cubilin and their ligands apoJ and apoAI in the female reproductive tract and to investigate if cubilin shares the same distribution of megalin. Our results show that: 1) apo J and apoAI are secreted by the uterine glands and internalized by the uterine epithelium during estrous and metestrous; 2) megalin is maximally expressed at estrous and metestrous; 3) cubilin exhibits the same distribution than megalin; 4) apoJ and apoAI staining is weak in the epithelial lining of the distal oviduct particularly at estrous, 5) the staining of cubilin and megalin is strong and granular near the apex of the epithelial lining of the distal oviducts. In conclusion, the observed pattern of expression of megalin, cubilin, apo AI and apo J is consistent with their playing joint roles in the process of capacitation.
KEY WORDS: megalin, clusterin, capacitation, cubilin