The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia.
Mice homozygous for a mutant allele (an/an) causing a lifelong macrocytic anemia (Hertwig's anemia) also demonstrate an inability to deliver their offspring, despite normal ovulation, conception, implantation, and fetal development. We investigated the roles of estrogen and relaxin in the etiology of the reproductive defect in the Hertwig's anemia mice. Immunoreactive relaxin levels were undetectable in the nonpregnant controls, whereas levels in both timed-pregnant controls and timed-pregnant affected mice were significantly higher than in nonpregnant controls, but not significantly different from each other. Mean interpubic ligament length in the pregnant Hertwig's anemia mice was significantly greater than that in nonpregnant controls, but significantly less than that in the pregnant controls on Day 18 of pregnancy. Porcine relaxin was administered to nonpregnant affected and unaffected littermates and to nonpregnant controls. Whereas controls showed a significant response to porcine relaxin, neither the Hertwig's anemia mice nor their unaffected littermates responded to the porcine relaxin. Additional study was performed to determine estradiol effects in the affected and control animals utilizing detailed computerized morphometric analysis of uterine horns and cervices from immature, estradiol-injected controls and Hertwig's anemia mice. Results demonstrated a statistically significant trophic effect of estradiol upon uterine horn and cervical enlargement, as assessed by weight and volume, in controls. Only a slight, non-significant effect was seen in Hertwig's anemia mice. Additional histological effects of estradiol, including endometrial enfolding observed in controls, were not present in Hertwig's anemia mice. Lack of response to both estrogen and relaxin is responsible for the parturitional defect in Hertwig's anemia mice.
Taney
F H
FH
Department of Obstetrics and Gynecology, UMDNJ-New Jersey Medical School, Newark 07103.
Vasilenko
P
P
Steinetz
B G
BG
Weiss
G
G
Cole
D
D
Goldsmith
L T
LT
D000748:Anemia, Macrocytic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D007744:Obstetric Labor Complications / Q000209:etiology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012065:Relaxin / Q000494:pharmacology / Q000502:physiology*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D004967:Estrogens; D004958:Estradiol; D012065:Relaxin