| dc.description.abstract | Endogenous retroviruses (ERVs) account for a substantial portion of the genetic
pool of every animal species (e.g. ~ 8% of the human genome). Despite their
overwhelming abundance in nature, many questions on the basic biology of ERVs are
unanswered. Sheep harbor approximately 20 copies of endogenous betaretroviruses
(enJSRVs), which are related to an exogenous oncogenic virus, Jaagsiekte sheep
retrovirus (JSRV). Therefore, they are an attractive model for investigation of the
potential beneficial roles of ERVs in reproductive biology.
Studies were conducted to determine: 1) expression of enJSRVs envelope (env)
and HYAL2 mRNAs in the ovine uterus and conceptus (embryo/fetus and
extraembryonic membranes) throughout gestation; 2) regulation of enJSRVs expression
by progesterone; and 3) the role of enJSRVs in regulating peri-implantation placental
growth and differentiation.
Study One determined the localization of enJSRVs env and HYAL2 mRNAs
throughout gestation. Results demonstrate that alterations in expression of enJSRVs and
HYAL2 in the sheep uterus and placenta suggest the probability of a variety of
physiological roles in implantation and placentation. Partial sequencing of the transcriptionally active enJSRVs from ovine uteroplacental tissues revealed expression
of multiple enJSRV loci.
Study Two assessed the influence of progesterone, interferon tau, and pregnancy
stage on enJSRVs expression, as an effort to understand factors that may regulate
enJSRVs. Results of this study support the hypothesis that expression of enJSRVs is
modulated by progesterone, but not IFNτ in vivo.
Study Three provides for enJSRVs regulating trophectoderm growth and
differentiation in the peri-implantation conceptus. Blocking conceptus enJSRVs Env
expression compromised pregnancy by retarding trophoblast outgrowth and
differentiation. Inhibition of enJSRVs Env in vitro also reduced proliferation of
mononuclear trophectoderm cells. Consequently, these results demonstrate that
enJSRVs Env regulates trophectoderm growth and differentiation in the ovine conceptus,
strongly supporting the biological significance of ERVs in placental evolution and
animal reproduction
Collectively, these studies illustrate that enJSRVs play an integral role in success
of pregnancy. While the definitive roles of the enJSRVs have not yet been elucidated, it
is evident that enJSRVs are an important component of the ovine genome and that they
influence recognition and maintenance of pregnancy and placental formation. | en |
