reproductive system
|
|
(J:91352)
(J:145805)
|
|
|
• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
|
|
|
• at P21, the number of primary follicles is significantly decreased
|
|
|
• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
|
|
|
• at P21, the number of small pre-antral follicles is significantly decreased
|
|
|
• at P21, the number of antral follicles is significantly decreased
|
|
|
• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
|
|
|
• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
|
|
|
• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
|
|
|
• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
|
|
|
• at E14.5, testes display delayed organization of the testes cords
|
small testis
(
J:91352
)
|
|
• at E14.5 and E16.5, testes are significantly smaller than wild-type
|
|
|
• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
|
cryptorchism
(
J:91352
)
|
|
• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
|
|
|
• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
|
|
• at 8-10 weeks of age, uterine histology revealed a reduction in epithelial, myometrial, and stromal layers
|
|
|
• the glandular elements of the endometrial layer appear less complex
|
|
|
• endometrial glands exhibit a less differentiated glandular structure than in control uteri
|
|
|
• only a few scattered endometrial glands are detected in the stroma
|
|
|
• at 8-10 weeks of age, uterine weight is significantly lower than in control females
|
|
|
• spermatogonia fail to develop into mature sperm
|
|
|
• male mice display significantly hypoplastic internal genitalia
|
|
• both male and female mice display no postnatal sexual maturation
• however, both male and female mice exhibit normal external genitalia at birth
|
|
|
• absence of corpora lutea indicates impaired ovulation
|
|
|
• after gonadotropin-induced ovulation, 8- to 12-wk-old females ovulate an average of only 1.0 +/- 0.7 oocytes per female versus 35.3 +/- 2.9 oocytes per female in wild-type controls (i.e. females heterozygous for the Nr5a1tm2Klp allele but negative for the Amhr2tm3(cre)Bhr allele)
• following superovulation induction, 80% of females had no oocytes retrieved from the oviducts; 2 females released 3 and 4 oocytes each, some found in immature stages of development
|
|
|
• estrous cycles range from abnormally prolonged cycles (50%) to complete acyclicity (50%)
|
short estrus
(
J:145805
)
|
|
• when observed, estrous phase length is significantly shorter than in control females
|
|
|
• 50% of females are completely acyclic
|
|
|
• 50% of females show abnormally prolonged cycles
|
|
|
• female mice are sterile
(J:91352)
• when mated with young wild-type male mice, no adult females delivered any pups during a >1 yr observation period
(J:145805)
|
|
|
• male mice are sterile
|
endocrine/exocrine glands
|
• adrenal glands are smaller than wild-type but appear histologically intact
|
|
|
• the glandular elements of the endometrial layer appear less complex
|
|
|
• endometrial glands exhibit a less differentiated glandular structure than in control uteri
|
|
|
• only a few scattered endometrial glands are detected in the stroma
|
|
|
(J:91352)
(J:145805)
|
|
|
• adult ovaries show a reduction in the total number of ovarian follicles
(J:91352)
• at P21 (just before the initiation of puberty), the number of growing follicles as well as the total number of follicles is significantly reduced
(J:145805)
|
|
|
• at P21, the number of primary follicles is significantly decreased
|
|
|
• at P21, the number of primordial follicles (the primordial follicle pool) is significantly decreased
• decreased reserve of follicles persists into adulthood
|
|
|
• at P21, the number of small pre-antral follicles is significantly decreased
|
|
|
• at P21, the number of antral follicles is significantly decreased
|
|
|
• adult ovaries exhibit the normal range of follicles up to the preovulatory stage but no corpora lutea, suggesting a defect in the final steps of folliculogenesis and/or ovulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• adult ovaries weigh significantly less than those from wild-type controls (1.79 +/- 0.15 mg versus 7.39 +/- 0.52 mg)
|
|
|
• adult ovaries are normally positioned adjacent to the oviducts but appear hypoplastic
(J:91352)
• however, at E14.5 and E16.5, ovaries and internal genital structures show no differences in size or histology relative to wild-type ovaries
(J:91352)
(J:145805)
|
|
|
• in adult males, the lumens of the seminiferous tubules fail to open, suggesting impaired Sertoli cell secretion of fluid
|
|
|
• at E14.5, testes are located adjacent to the kidneys but are significantly smaller and do not contain distinct testes cords
• at E16.5, testes remain smaller than wild-type testes but have organized into testicular cords
• delayed testis development is associated with decreased Leydig cell expression of essential components of testosterone biosynthesis
|
|
|
• at E14.5, testes display delayed organization of the testes cords
|
small testis
(
J:91352
)
|
|
• at E14.5 and E16.5, testes are significantly smaller than wild-type
|
|
|
• adult male mice display significantly hypoplastic testes
• at E14.5 and E16.5, decreased testis size is associated with reduced cell proliferation in somatic cells of the testes
|
cryptorchism
(
J:91352
)
|
|
• testes remain at the level of the bladder within the abdominal cavity
• however, no structures derived from the Mullerian ducts (such as oviducts or uterus) are observed
|
|
|
• adult ovaries show significantly reduced basal and eCG-stimulated expression of Amh (anti-Mullerian hormone) as well as decreased eCG-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2) relative to control ovaries
• in contrast, ovaries exhibit increased basal expression of Inha (inhibin-alpha) but -- unlike control ovaries -- fail to show increased Inha expression in response to eCG stimulation
|
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
|
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
homeostasis/metabolism
|
• adult males exhibit plasma testosterone levels that are indistinguishable from those of prepubertal wild-type males
|
|
|
• in response to eCG stimulation, 8-12-wk-old females show a significantly blunted increase in plasma estradiol levels relative to control females
• however, basal plasma estradiol levels are normal
|
|
|
• basal plasma FSH levels are significantly higher than in wild-type females
|
growth/size/body
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|
cellular
|
|
• granulosa cells of growing follicles show significantly reduced expression of CCND2 (cyclin D2) and MKI67 (Ki67) but increased expression of CDKN1B (p27), suggesting impaired granulosa cell proliferation
|
cardiovascular system
|
|
• the few remaining ovarian follicles contain hemorrhagic cysts
|


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