PARENT SESSION
Gonadal Function
349
PRENATAL EXPOSURE TO GALACTOSE ADVERSELY AFFECTS GERM CELL MIGRATION POSSIBLY BY WAY OF INHIBITING URIDINE DIPHOSPHATE GALACTOSE 4-EPIMERASE ACTIVITY IN RATS.
Bandyopadhyay, Soma1, Chakrabarti, Jana 1, Bhattacharyya, Debasish1, Chakravarty, Baidyanath2, Kabir, Syed1, 1 2
ABSTRACT- In rat, prenatal exposure to high galactose concentration through a galactose-rich diet may contribute to the premature ovarian failure (POF) component of human galactosemia. We observed that migration of primordial germ cells (PGC) is adversely affected in embryos from high galactose fed mother. PGC possess a unique N-acetylgalactosamine (GalNac)-containing glycoconjugate on their surface, which is of functional importance in regulating the guidance and locomotion of these cells during the course of their extensive migration. The present study explores if prenatal exposure to high galactose concentration affects the activity of uridine diphosphate galactose 4-epimerase, the enzyme involved in the inter-conversion between UDP-glucose and UDP-galactose in the process of biosynthesis of GalNac. Pregnant rats were fed commercial pellets supplemented with, or without 35% galactose from day 3 of conception (presence of spermatozoa in vaginal lavage = day 1) continuing through parturition. On day 11, rats were laparotomized under light ether anesthesia. Embryos from one uterine horn were dissected out. They were fixed, processed and stained for histochemical localization of PGC on the basis of binding of horseradish peroxide-conjugated Dolichos biflorus (DB), a lectin specific for GalNac. The embryos of the other uterine horn were maintained until parturition. The liver content of crude epimerase activity of 1-2 day old pups was assayed according the coupled assay procedure, and was expressed as Beckman Unit (0.001 O.D.)/mg protein. In day 11 control embryos, DB reactivity evidencing terminal GalNac was observed in PGC scattered singly or in clusters along the posterior epithelium and caudal to the epithelium of the hind gut. In the galactose-exposed group, no DB reactivity was apparent at the expected sites in ~ 20% of embryos, while the rest exhibited comparatively lower number of PGC. As compared to that of the control, liver epimerase activity was reduced to ~60% (control: 157+/-36 vs. gal-fed: 97+/-12).We conclude that under galactosemic state germ cell migration may be impaired as a consequence of impaired epimerase activity; and an eventual deficient initial pool of germ cells in the gonad may be one of the causal links between galactosemia and POF.
KEY WORDS: galactosemia, premature ovarian failure, germ cell migration, epimerase activity