An estrogen-dependent secretory protein, which shares identity with chitinases, is expressed in a temporally and regionally specific manner in the sheep oviduct at the time of fertilization and embryo development.

Abstract

An estrogen (E2)-dependent 90,000-92,000 M(r) protein is synthesized and released by the sheep oviduct in a temporally and regionally specific manner during the first few days of pregnancy, where it associates with the embryo. The present study was undertaken to further define the nature of this protein and its regulation at a time when fertilization and early embryonic cleavage occur in the oviduct. The complete complementary DNA (cDNA) sequence for the 90,000-92,000 M(r) protein was determined, and steady state messenger RNA (mRNA) levels were measured during early pregnancy (estrus and days 1, 2, 3, 4, 6, and 16). The composite cDNA possessed an open reading frame of 1633 bases with a single potential N-glycosylation site. The inferred amino acid (aa) sequence predicted a prepolypeptide of 539 aa (69,151 M(r)) and a mature polypeptide of 518 aa (66,477 M(r)). Nucleotide and deduced aa sequence shared identity with translated E2-dependent cow, human, and partially sequenced baboon oviduct protein cDNAs; a human articular cartilage protein, gp 39; and chitinases. Northern blot hybridization revealed a single RNA species (2.2 kilobases) in the fimbria and ampulla, which was not detected in the isthmus or other reproductive and nonreproductive tract tissue RNAs. Steady state levels of mRNA encoding the 90,000-92,000 M(r) were highest in the fimbria and ampulla at estrus and on day 1 of pregnancy, when gamete transport and fertilization occur in the E2-dominated fallopian tube. Oviduct protein mRNA levels declined significantly (P < 0.05) on day 2 and underwent a further significant reduction on day 3 of pregnancy coincident with transport of the embryo from the oviduct to the uterus, a reproductive stage associated with rising progesterone levels. By day 16 of pregnancy, the mRNA encoding the E2-dependent oviduct protein was virtually undetectable. The temporally and regionally specific regulation of gene expression for the 90,000-92,000 M(r) E2-dependent protein correlates with protein synthesis data and emphasizes the precise regulation of its synthesis at a time when fertilization and embryonic cleavage are taking place in the oviduct. Identity with a growing class of steroid-regulated oviduct secretory proteins and chitinase enzymes suggests a possible structural and/or functional relationship, which may be important in mediating these latter reproductive events.

Epithelial Lining of the Sheep Ampulla Oviduct Undergoes Pregnancy-Associated Morphological Changes in Secretory Status and Cell Height1

“…The lamellar secretory granules have been shown to be the cellular source of highmolecular-weight E 2 -dependent oviduct secretory glycoproteins [5,7,18,211. Molecular cloning has recently demonstrated that these E 2 -dependent glycoproteins represent a family of oviduct-specific macromolecules that share nucleotide and primary amino acid sequence identity [13,. Collectively, these data show that the oviducts of several mammalian species synthesize, store, and export comparable secretory products in a similar biosynthetic and cytological manner.…”

“…The secretory activity of the sheep ampulla oviduct is modified in response to E 2 and progesterone (P) and during early pregnancy [5,6]. An E 2 -dependent M, 90 000-92 000 glycoprotein is expressed, synthesized, and released by the ampulla at the time of fertilization and early embryonic cleavage and prior to a systemic rise in serum P levels [6,13] where it associates with the fertilized ovum [14]. Changes in the secretory status of the sheep ampulla that occur during the first few days of pregnancy are likely to be accompanied by changes in the protein-synthesizing organelles of nonciliated epithelial cells.…”

Human enzymatic activities related to the therapeutic administration of chitin derivatives

“…This is the case for estrogen-dependent secretory proteins from sheep, human, baboon, cow, pig and hamster, expressed in a temporally and regionally specific manner in the oviducts at the time of fertilization and embryo development. Alignments of their aminoacid sequences showed various degrees of identity (from 26 to 36%) to chitinase [36]. mRNA for human cartilage gp-39 is present in human articular chondrocytes as well as in liver, but not in muscle, lung, pancreas, mononuclear cells or fibroblasts.…”

Expression of C-20, 22 Desmolase Activity by the Human Fallopian TubeIn Vitro: Evidence for Steroidogenesis

“…ries its own genomic program of developmental events from the first mitotic division 1221, steroid hormone induced glycoproteins are elaborated by the Fallopian tubes imparting an embryotrophic role [23,24]. The identification and characterization of pregnenolone in this study implicates a steroidogenic role for Fallopian tubes necessary for the release of oviductal glycoproteins, which facilitate fertilization and subsequent embryo cleavage.…”