| dc.description.abstract | Endogenous retroviruses (ERVs) comprise a significant portion of the genome of
all mammals and have been implicated in placental development in multiple species.
The ovine genome contains approximately 27 copies of endogenous betaretroviruses
(enJSRVs) that are related to the exogenous Jaagsiekte sheep retrovirus (JSRV), an
oncogenic retrovirus tropic to the lung. The enJSRV loci are abundantly expressed in
the female reproductive tract and the conceptus, and they are essential to conceptus
development.
Studies were conducted to determine: 1) the effect of exogenous progesterone
administration on conceptus development after loss of enJSRV Env; 2) the specific
enJSRV env expressed in the developing conceptus; and 3) if the uterus produces
enJSRV viral particles that are capable of transducing the conceptus.
Study One determined the effects of exogenous progesterone on development of
the conceptus in which enJSRV Env was ablated. Despite rescuing conceptus survival,
the conceptuses were morphologically fragile and had reduced binucleate cell (BNC)
numbers. These results suggest that mononuclear trophectoderm cell (MTC) proliferation and differentiation is dependent on enJSRV Env, even in a uterine
environment supported by exogenous progesterone.
Study Two assessed the enJSRV loci transcribed in the ovine conceptus during
elongation before (day 13) and after (day 18) onset of BNC differentiation. The most
represented loci in both day 13 and day 18 conceptuses encoded truncated Env proteins
that did not contain membrane-spanning domains. Conceptuses from both time points
contained evidence of the transcription of full-length, biologically active enJSRV Env,
as well as completely intact proviral loci with the ability to produce viral particles in
vitro.
Study Three utilized a transpecies embryo transfer experiment to determine if the
intact enJSRVs loci could produce viral particles in vivo. The presence of enJSRV viral
particles in the uterus was confirmed, as was their ability to transduce the conceptus.
Collectively, these studies provide evidence of truncated Env proteins, intact
biologically active Env proteins, and enJSRVs viral particles within the ovine uterus and
conceptus that are necessary to stimulate proliferation and differentiation of MTCs even
in a uterine environment supported by exogenous progesterone. | en |
