Year: 2004
Type: article
Abstract: Transforming Growth Factor ß1 (TGFß1) is essential for normal female reproduction. Mice with a targeted deletion in the TGFß1 gene (TGFß1–/–) have severely impaired fertility with pregnancy occurring in <25% of mated females. TGFß1 is implicated in several aspects of ovarian function, including potentiation of granulosa cell proliferation and suppression of luteal cell apoptosis. Our initial observations indicate that estrous cycling is disrupted in TGFß1–/– mice and that ovulation rate is reduced. To further investigate how impaired ovarian function contributes to the infertility of TGFß1–/– mice, ovaries were isolated from TGFß1+/+ and TGFß1–/– littermates at proestrus and fixed and sectioned for examination of follicle morphology and growth. BrdU labelling was performed to detect granulosa cell proliferation and blood samples were obtained for analysis of gonadotrophins and ovarian steroid hormones. Histological examination showed that ovaries from TGFß1–/– mice were smaller than those of TGF–1+/+ mice, however large antral follicles were observed, indicating that TGFß1 is not essential for granulosa cell proliferation. Compared to TGFß1+/+ ovaries however, there were fewer antral follicles and only rare corpora lutea. Interestingly, in some cases there were large numbers of macrophages surrounding small follicles suggesting increased follicular atresia and/or altered macrophage activity in the TGFß1–/– ovaries. Ovaries and serum were also isolated from females at d4 post-coital for assessment of corpora lutea morphology. TGFß1–/– ovaries weighed less and had fewer corpora lutea than TGFß1+/+ ovaries. TGFß1–/– corpora lutea also contained increased numbers of apoptotic cells and infiltrating macrophages indicative of premature luteal regression. Circulating progesterone levels were reduced in TGFß1–/– females, as was progesterone production per corpus luteum further indicating a functional defect in luteal maintenance. Cumulatively these observations show that TGFß1 has essential roles in regulation of ovarian macrophage populations, in normal follicular development and in the generation, maintenance and steroidogenic function of corpora lutea.
DOI: 10.1071/srb04abs220
Authors: R. L. Robker, W. V. Ingman, S. A. Robertson
Institution: The University of Adelaide
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2049624836