Hypothyroid induced reproductive malfunction in both the sexes is a common phenomenon of global concern. In an attempt to characterize the differentially expressed genes that might be responsible for these disorders, we have identified a number of clones in hypothyroid rat ovary by subtractive hybridization. One of such clones is procollagen lysyl hydroxylase2 (Plod-2), the key enzyme for the first step of collagen biosynthetic pathway, which was down regulated in hypothyroid condition. We have also demonstrated the reduced expression of other isoforms of Plods, namely Plod1 and 3 in hypothyroid rat ovary. The current studies are the first of its kind to report that thyroid hormone regulates the Plod gene in rat ovary. Moreover, we have shown the up-regulation of matrix degrading enzyme(s), matrix metalloproteinase(s) in hypothyroid rat ovary, whereas the tissue inhibitory metalloproteinase is down regulated. Finally, the results of the present studies indicate that in hypothyroid condition collagen biosynthesis in ovary seems to be disturbed with concomitant enhancement in collagen degradation resulting in disintegration of overall ovarian structure.