Postnatal development of the uterus involves, particularly, development of uterine glands. Studies with ovariectomized ewe lambs demonstrated a role for ovaries in uterine growth and endometrial gland development between postnatal days (PNDs) 14 and 56. The uterotrophic ovarian factor(s) is presumably derived from the large numbers of growing follicles in the neonatal ovary present after PND 14. The Inverdale gene mutation (FecXI) results in an increased ovulation rate in heterozygous ewes; however, homozygous ewes (II) are infertile and have ‘streak’ ovaries that lack normal developing of preantral and antral follicles. Uteri were obtained on PND 56 to determine whether postnatal uterine development differs between wild-type (++) and II Inverdale ewes. When compared with wild-type ewes, uterine weight of II ewes was 52% lower, and uterine horn length tended to be shorter, resulting in a 68% reduction in uterine weight:length ratio in II ewes. Histomorphometrical analyses determined that endometria and myometria of II ewes were thinner and intercaruncular endometrium contained 38% fewer endometrial glands. Concentrations of estradiol in the neonatal ewes were low and not different between ++ and II ewes, but II ewes had lower concentrations of testosterone and inhibin-α between PNDs 14 and 56. Receptors for androgen and activin were detected in the neonatal uteri of both ++ and II ewes. These results support the concept that developing preantral and/or antral follicles of the ovary secrete uterotrophic factors, perhaps testosterone or inhibin-α, that acts in an endocrine manner to stimulate uterine growth and endometrial gland development in the neonatal ewes.
Kanako Hayashi, Anne R O'Connell, Jennifer L Juengel, Ken P McNatty, George H Davis, Fuller W Bazer and Thomas E Spencer
Zaramasina L Clark, Derek A Heath, Anne R O’Connell, Jennifer L Juengel, Kenneth P McNatty and Janet L Pitman
Ewes with single copy mutations in GDF9, BMP15 or BMPR1B have smaller preovulatory follicles containing fewer granulosa cells (GC), while developmental competency of the oocyte appears to be maintained. We hypothesised that similarities and/or differences in follicular maturation events between WT (++) ewes and mutant ewes with single copy mutations in BMP15 and BMPR1B (I+B+) are key to the attainment of oocyte developmental competency and for increasing ovulation rate (OR) without compromising oocyte quality. Developmental competency of oocytes from I+B+ animals was confirmed following embryo transfer to recipient ewes. The microenvironment of both growing and presumptive preovulatory (PPOV) follicles from ++ and I+B+ ewes was investigated. When grouped according to gonadotropin-responsiveness, PPOV follicles from I+B+ ewes had smaller mean diameters with fewer GC than equivalent follicles in ++ ewes (OR = 4.4 ± 0.7 and 1.7 ± 0.2, respectively; P < 0.001). Functional differences between these genotypes included differential gonadotropin-responsiveness of GC, follicular fluid composition and expression levels of cumulus cell-derived VCAN, PGR, EREG and BMPR2 genes. A unique microenvironment was characterised in I+B+ follicles as they underwent maturation. Our evidence suggests that GC were less metabolically active, resulting in increased follicular fluid concentrations of amino acids and metabolic substrates, potentially protecting the oocyte from ROS. Normal expression levels of key genes linked to oocyte quality and embryo survival in I+B+ follicles support the successful lambing percentage of transferred I+B+ oocytes. In conclusion, these I+B+ oocytes develop normally, despite radical changes in follicular size and GC number induced by these combined heterozygous mutations.