Gene therapy for haemophilia: how far have we come?
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Adenoviruses, Human↗
Biomedical subjects
P A Fields
Publications and source records attributed to P A Fields.
Glial cell-specific differences in response to alkylation damage.
Oligodendrocytes are preferentially sensitive to the toxic, carcinogenic, and teratogenic effects of methylnitrosourea (MNU). The mechanisms responsible for this enhanced sensitivity have not been fully elucidated. One of the most vulnerable cellular targets for this chemical is mitochondrial DNA (mtDNA). To determine if differences in mtDNA damage and repair capacity exist among the different CNS glial cell types, the effects of MNU exposure on oligodendroglia, astroglia, and microglia cultured separately from neonatal rat brain were compared. Quantitative determinations of mtDNA initial break frequencies and repair efficiencies showed that whereas no cell type-specific differences in initial mtDNA damage were detected, mtDNA repair in oligodendrocytes, oligodendrocyte progenitors, and microglia was significantly reduced compared to that of astrocytes. In astrocytes, and all other cell types previously evaluated in our laboratory, >60% of N-methylpurines were removed from the mtDNA by 24 hr. In contrast, only 35% of lesions were removed from mtDNA of oligodendrocytes, oligodendrocyte progenitors, and microglia during the same time period. Mitochondrial perturbations by a variety of xenobiotics have been linked to apoptosis. In the present study, apoptosis, as determined by DNA laddering and ultrastructural analysis, was clearly induced by MNU treatment of cultured oligodendrocyte progenitors and microglia, but not in astroglia. These data demonstrate a correlation between diminished mtDNA repair capacity and the induction of apoptosis. However, further experimentation is necessary to determine if a causal relationship exists and contributes to the vulnerability of oligodendroglia following exposure to N-nitroso compounds in the environment or in chemotherapeutic regimen.
Alkylating Agents↗
Relaxin: an ovarian hormone in an avian species (Gallus domesticus).
The objective of this study was to characterize the biochemical, immunological, and biological activity of avian relaxin and to immunolocalize relaxin-like peptides in the ovary of the hen (Gallus domesticus). A relaxin-like peptide was partially purified from ovaries of actively laying hens by size-exclusion chromatography and further purified by ion-exchange chromatography on CM-cellulose. Those fractions containing relaxin immunoreactivity were identified with the use of a homologous porcine relaxin radioimmunoassay on selected column effluent and pooled, and a sample was subjected to SDS-gel electrophoresis. The SDS-gel-separated proteins were electrotransferred onto a nitrocellulose membrane and immunostained with an antiserum to porcine relaxin which showed the presence of a single band of approximately 6000 daltons. The dose-response curve generated by avian relaxin-like peptide in the homologous porcine relaxin radioimmunoassay was parallel to that produced by the porcine relaxin standard. Like porcine relaxin, avian relaxin-like peptide eluted from the Sephadex G-50 in an elution volume for a molecule of approximately 6000 daltons, was retained on CM-cellulose, and was bioactive in in vitro inhibition of spontaneous contractions of estrogen-primed mouse uterus (a relaxin bioassay). Using an antiserum specific to porcine relaxin, avian relaxin-like peptide was immunolocalized to the granulosa cells of postovulatory follicle from ovary of a hen less than 24 hr postoviposition. No immunostaining was detected in the cells of the largest preovulatory follicles or when the antiserum was preabsorbed with porcine relaxin prior to staining. The finding of this study indicates that the avian postovulatory follicle, like the corpus luteum of other vertebrate species (sharks and mammals), contains a relaxin-like peptide.
Animals↗
Synthesis and messenger ribonucleic acid expression of apolipoproteins E and A-I by the bovine corpus luteum during the estrous cycle and pregnancy.
In an attempt to characterize proteins secreted by the corpus luteum, explant cultures of luteal slices from cows taken on Days 3, 7, 11, 14, 17, and 19 of the estrous cycle, and Days 17, 88, 180, and > 240 of pregnancy were incubated with H-leucine for 24 h. Proteins in luteal-conditioned medium were separated by two-dimensional PAGE, transferred to polyvinylidene fluoride membrane, and subjected to N-terminal amino acid microsequencing. Microsequence analysis revealed that the bovine corpus luteum synthesized and released de novo synthesized apolipoproteins (Apo) E and A-I in culture during the estrous cycle and pregnancy. Release of Apo E was observed only on Day 3 of the estrous cycle. Release of Apo A-I was observed on Days 11, 14, 17, and 19 of the estrous cycle, and on all days of pregnancy examined. To demonstrate the presence of the appropriate mRNA and characterize the temporal relationship for these identified proteins, total RNA was isolated from corpora lutea on Days 2, 3, 7, 16, 17, and 20 of the estrous cycle, and on Days 17, 90, 170, 180, and 272 of pregnancy, and submitted to Northern and dot blot analysis. Apo E mRNA was expressed only on Days 2-3 of the estrous cycle and was not expressed on the other days of the cycle or during pregnancy. A single Apo E mRNA transcript about 1.0 kilobase (kb) in size was observed. Expression of Apo A-I mRNA was detected on all days of the estrous cycle and pregnancy examined. Apo A-I cDNA hybridized with a single mRNA transcript about 1.0 kb in size. Apo A-I mRNA levels did not differ among days of the estrous cycle, although higher levels of Apo A-I mRNA were observed during later stages of pregnancy. Serum concentrations of Apo A-I and progesterone were correlated across the estrous cycle but not during the prepartum period or after parturition. This study demonstrates for the first time that the corpus luteum synthesizes Apo E and Apo A-I and expresses their respective mRNAs. The pattern of expression of Apo E and Apo A-I mRNAs paralleled that of de novo synthesis of their respective proteins after incubation of luteal tissue with [H]leucine. The role of luteal apolipoproteins may involve an autocrine/paracrine function influencing luteal development, tissue remodeling, and steroidogenesis.
Amino Acid Sequence↗
Morphological characteristics of the bovine corpus luteum during the estrous cycle and pregnancy.
The corpus luteum, one of the biological clocks of the estrous cycle and pregnancy, is known foremost for its production of progesterone that blocks the pituitary release of gonadotropins and prepares the uterus for a pregnancy. The cellular sources of this progesterone are the steroidogenic small and large luteal cells. Other luteal cells that are not steroidogenic, but are believed to have an important role in the function of this gland are the fibroblast, macrophages and endothelial cells. The most prominent luteal cell is the large steroidogenic cell characterized by an abundance of smooth endoplasmic reticulum and densely packed spherical mitochondria that are indicative of its contribution to most of the circulating progesterone believed to be constitutively secreted and not under the control of LH. Other distinguishing features of the large luteal cell are the presence of rough endoplasmic reticulum, prominent Golgi, and secretory granules that are indicative of endocrine cells. This cell undergoes dynamic changes across the estrous cycle and pregnancy, believed to reflect a change in progesterone and protein secretion that will eventually influence a successful pregnancy or another ovulation if pregnancy fails. The morphological characteristics of the bovine luteal cells are the focus of this review.
Journal Article↗
Oxytocin receptors in bovine cervix: distribution and gene expression during the estrous cycle.
Oxytocin (OT) receptor (OTR) concentrations were determined in the cervix of nonpregnant cows on cycle Days 0, 3, 7-8, 17, and 19 (n = 3-4 cows each day); [3H]OT was used as the labeled ligand. Mucosal and muscle layers of the cervix were also analyzed separately for both ligand binding and expression of the OTR gene using a newly developed RNase protection assay (RAP). Cellular localization of OTR protein was determined by immunohistochemistry. All regions of cervix from cows at estrus had high concentrations of OTR; in the luteal phase, all were sharply down-regulated. At estrus the mucosal layer had about 30-fold higher concentrations than the muscle layer. OTR mRNA was readily detected by RAP in the mucosa from estrous cows, while much weaker signals were found in the muscle. On Days 7-17, the OTR mRNA signals in both mucosa and muscle were very faint or nondetectable. Thus, there was a good correlation between ligand binding and mRNA expression, which suggests that OTR concentrations are mainly regulated at the transcriptional level. The epithelial cells at the luminal surface of the mucosa were the principal site of immunoreactive OTR; muscle cells showed significantly weaker signals. Previously, OT was found to stimulate prostaglandin (PG) E2 output in vitro in bovine cervical tissues. Since PGE2 is capable of softening the cervix, our findings suggest that OT may have a novel physiological function to cause softening of the bovine cervix mediated by the release of PGE2.
Animals↗
A cellular and endocrine characterization of the original and induced corpus luteum after administration of a gonadotropin-releasing hormone agonist or human chorionic gonadotropin on day five of the estrous cycle.
To determine whether injection of hCG or GnRH-agonist on d 5 after estrus (d 0) has a differential functional effect on an induced and the original corpus luteum (CL), two experiments were conducted. In Exp. 1, nonlactating Holstein cows were injected on d 5 with saline (n = 4; T1), a GnRH-agonist (Buserelin, 8 micrograms i.m.; n = 4; T2), or hCG (1,000 i.u., i.v., and 2,000 i.u., i.m.; n = 4; T3). Induced CL were removed on d 13 and weights were different (GnRH-agonist < hCG). In vitro production of progesterone by CL tissue (microgram/g; microgram/CL) was affected by treatment (GnRH-agonist < hCG) and dose of LH (ng.mL) in culture media. Experiment 2 was a replicate of Exp. 1, except that the original CL was removed on d 17 for in vitro culture. Day-17 CL weights and in vitro production of progesterone by original CL were not affected by treatment. The daily rate of increase of plasma progesterone from d 6 to d 13 differed: saline < GnRH-agonist < hCG (P < .01). From d 14 to 17, the rate of plasma progesterone decrease was not different between treatments. Electron micrographic study of the original and induced CL indicates that LH-like exposure delays involution of steroidogenic luteal cells. In summary, the higher levels of progesterone from d 6 to d 13 of the estrous cycle following an injection of hCG vs GnRH-agonist on d 5 is due to a greater response of hCG-induced CL.
Animals↗
Cellular distribution of lesions in Batten disease.
One of the characteristic manifestations of chronic neuronal lipofuscinosis (Batten disease) is a marked predisposition for epileptic seizures. The management of these seizures is very difficult. The present study was initiated to determine what mechanisms could account for the seizure disorder. Tissue was examined from a patient with a history of Batten disease that was histologically verified. Reduced silver and Golgi impregnations were done on the parietal cortex of the patient. There was no evidence of the marked dendritic abnormalities seen in classic epileptic foci. Instead there was marked swelling and dilatation of the axon hillock and initial segment. This finding suggested that inhibition of these pyramidal neurons was markedly attenuated due to disruption of initial segment inhibitory synapses. Studies are continuing to determine if the GABA decreases seen in Batten disease may in part be due to trophic sequences brought about by loss of these critical inhibitory synapses.
Adolescent↗
In vitro transformation of rabbit cytotrophoblast cells into syncytiotrophoblast: stimulation of hormone secretion by progesterone and dibutyryl cyclic 3',5'-adenosine monophosphate.
Rabbit placenta syncytiotrophoblast cells exhibit immunostaining for the hormone relaxin. The objectives of this study were to evaluate the ability of cultured rabbit trophoblast cells to secrete immunoreactive (IR) relaxin and then to study the effects of progesterone, which is essential for maintenance of the placenta and of pregnancy in the rabbit, on that secretion. On Day 1, both treated and untreated trophoblast cell cultures consisted of 90% relaxin-negative mononuclear cells (cytotrophoblast and fibroblast) and 10% relaxin-positive multinuclear cells (syncytiotrophoblast). Media from untreated cultures, collected throughout 9 days of culture, contained low but constant levels of relaxin. Electron microscopy studies indicated that relaxin was localized in dense granules of the multinuclear cells and that these cells formed by fusion of mononuclear cytotrophoblast. Progesterone treatment (40 and 80 ng/ml) increased (p < 0.0001) media concentrations of relaxin, increased the number of desmosomes between cytotrophoblast cells (12 vs. 4 for controls on Day 5), and increased the percentage of multinuclear cells (73% of the cell population vs. 20% for controls on Day 7). Specificity of the progesterone effect was evaluated by treatment of cultures with dibutyryl cAMP (dbcAMP), insulin, hCG, estradiol-17 beta, prostaglandin E2, and prostaglandin F2 alpha. Only dbcAMP (2 mM and 4 mM) produced an increase (p < 0.0001) in media concentrations of relaxin. These results indicate that, like the intact placenta, cultured cytotrophoblast cells fuse to form syncytiotrophoblast and that the latter contain IR relaxin.
Animals↗
Insurance approaches for addressing home care liability.
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Home Care Services↗
Heavy metal intoxication from homeopathic and herbal remedies.
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Homeopathy↗
The physiological effects of relaxin during pregnancy: studies in rats and pigs.
For 50 years after its discovery in 1926, there was a general lack of interest in relaxin among both reproductive biologists and clinicians. A key reason for this lack of interest was the lack of information concerning relaxin's physiological importance during pregnancy in any species. Research conducted since the early 1980s has established that the hormone relaxin is essential during pregnancy in at least two species--rats and pigs. Two vital roles for relaxin during pregnancy have been identified. Relaxin promotes growth and softening of the uterine cervix and thereby enables rapid and safe delivery in both rats and pigs. Relaxin also promotes growth and development of the mammary apparatus in both species. Interestingly, the major effects of relaxin on mammary growth and development are targeted on the nipple in the rat, whereas they are targeted on the glandular parenchyma in the pig. Relaxin-dependent growth of the nipple in rats is required for normal lactational performance. Although likely, it remains to be established that relaxin's profound effects upon mammary gland development in pigs are required for normal lactational performance. The fact that relaxin has effects upon cervical and mammary gland development during pregnancy in both rats and pigs encourages the view that relaxin may have similar effects during pregnancy in other species. Nevertheless, one must keep in mind that there is great diversity in the physiology of relaxin among species (reviewed by Sherwood 1988). This diversity includes not only relaxin's source, regulation of synthesis and secretion, and secretory profiles during pregnancy, but also its biological effects. It seems essentially certain that relaxin's effects during pregnancy differ among species. For example, transformation of the pubic joint cartilage to a flexible and elastic interpubic ligament occurs during pregnancy in several species, including guinea pigs, mice, and bats. This pelvic adaptation, which is nearly certainly relaxin dependent, does not occur in species such as rats and sheep. It is possible that relaxin may have little or no physiological significance during pregnancy in some species. Although considerable progress has been made toward an understanding of the physiological role(s) of relaxin in pregnant rats and pigs, many fundamental questions remain unanswered.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Characterization of large luteal cells and their secretory granules during the estrous cycle of the cow.
Large steroidogenic cells of the bovine corpora lutea were evaluated for morphological changes on Days 3, 7, 11, 14, 17, and 19 of the estrous cycle. Large cells were readily identified by size (25-50 microns diameter), numerous mitochondria, and the presence of dense secretory granules (150-300 nm in diameter). These granules were found in a discrete cluster and were not dispersed throughout the cytoplasm. Only 3% of the large cells contained a cluster of granules on Day 3. The percentage was highest during midcycle (Day 7, 84%; Day 11, 64%), dropped on Day 14 (26%), and was lowest on Days 17 (16%) and 19 (8%). Electron microscopic immunocytochemistry showed that oxytocin and neurophysin were co-localized in these granules on all days evaluated. As early as Day 14, large cells were observed with characteristics typical of regressing corpora lutea, i.e., a reduction in cells with secretory granules, large cytoplasmic lipid droplets, and swollen mitochondria with dense inclusions. However, since this was a time of the cycle when plasma concentrations of progesterone were very high, this corpus luteum is referred to as involutive rather than regressive. Our results may be summarized as follows: 1) from Day 7 to Day 14 there was a 69% decline in the number of large cells containing oxytocin-laden secretory granules. This occurred prior to the rise in uterine oxytocin receptors and the large luteolytic pulses of prostaglandin that reportedly occur after Day 14. The role of this apparent early release of oxytocin is not known. 2) Large steroidogenic luteal cells of the estrous cycle have morphological characteristics similar to those of large luteal cells during pregnancy. However, large luteal cells of the estrous cycle contain oxytocin whereas those of pregnancy are devoid of oxytocin.
Animals↗
Monoclonal antibodies specific for rat relaxin. VI. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts histological changes associated with cervical softening at parturition in rats.
Relaxin, which is secreted by the corpora lutea throughout the second half of rat pregnancy, promotes the growth and softening of the cervix. The mechanisms at both the cellular and molecular levels by which relaxin brings about these effects remain to be determined. The present study examined the influence of endogenous relaxin on the histological changes associated with cervical softening. A monoclonal antibody for rat relaxin, designated MCA1, was injected iv daily on days 12-22 of gestation. Cervices were removed on day 22, fixed in 10% buffered formalin, embedded in paraffin, and processed for histological staining. Tissue sections (5 microns thick) were stained with Gomori's trichrome stain (collagen), Orcein stain (elastin), or periodic acid-Schiff (polysaccharide). Qualitative and quantitative analyses identified several histological parameters in MCA1-treated rats that differed markedly from those in control rats. Cervices obtained from MCA1-treated rats contained collagen fiber bundles with greater compactness; elastin fibers with greater density, length and interdigitation; arteries with smaller cross-sectional areas; and luminal involutions with smaller areas than controls. The cervices of MCA1-treated rats appeared to contain fewer vacuolated epithelial cells, which secrete polysaccharide-rich material, than did cervices obtained from controls. It seems plausible that most, if not all, of these relaxin-induced modifications of the histological characteristics of the cervix facilitate birth.
Animals↗
Evidence for a dual source of relaxin in the pregnant rat: immunolocalization in the corpora lutea and endometrium.
Uterine tissue was collected from intact pregnant rats on days 4, 10-15, 18, and 22 of pregnancy and day 2 postpartum and from rats on day 22 of pregnancy after ovariectomy (day 9) and progesterone-estrogen treatment. Placental, cervical, mammary, and pituitary tissues were collected from intact pregnant rats on day 22. Ovarian tissue was collected from intact pregnant rats on days 15, 20, and 22. These tissues were evaluated for relaxin immunostaining at the light microscope level using an antiserum to purified rat relaxin and the avidin biotin immunostaining technique. Since the corpus luteum is the major source of relaxin in the rat, this tissue was used as a positive control. Relaxin immunostaining in the corpus luteum was observed in a discrete region of the cytoplasm. This pattern of staining corresponded with the discrete clustering of relaxin-containing secretory granules found in the rat luteal cells. Relaxin was not observed in the day 22 placenta, cervix, mammary gland, pituitary gland, or day 4-13 pregnant uterus. Relaxin immunostaining was detected in endometrial epithelial cells on days 14-22 of pregnancy and day 2 postpartum. Relaxin immunostaining was more evident at implantation sites than between implantation sites. Antimesometrial epithelial cells at implantation sites contained relaxin immunostaining. The mesometrial surface, which consists of the placenta and decidualized endometrium, did not contain relaxin immunostaining. Relaxin immunostaining was also present in the endometrial epithelial cells of the day 22 pregnant rats that had been ovariectomized on day 9 and given subsequent replacement therapy with ovarian steroids. The presence of relaxin immunostaining in the ovariectomized rat indicates the endometrium is not sequestering relaxin secreted from the corpus luteum. These data provide evidence that the pregnant rat endometrium is a source of relaxin in addition to the corpus luteum. The appearance of relaxin in endometrial epithelial cells after implantation and its prominence at implantation sites may indicate that locally secreted conceptus factors stimulate endometrial relaxin synthesis.
Animals↗
Conceptus-mediated integrity of endometrial epithelial cells and maintenance of relaxin synthesis in pregnant rabbits: effects of unilateral oviduct ligation.
A previous study indicated rabbit endometrial relaxin synthesis is stimulated by blastocyst (Lee VH, Fields PA, Biol Reprod 1990; 40:737-745). To evaluate this hypothesis, unilateral oviduct ligations were placed (A) at the oviduct isthmus on Day 1 post-copulation and (B), in a separate group of rabbits, at the infundibulum before copulation. Blastocysts migrate into and implant in the uterine horn contralateral to the ligated oviduct only (conceptus-bearing uterus). The uterine horn ipsilateral to the ligated oviduct will be referred to as the non-conceptus-bearing uterus. Uteri and ovaries were removed on Days 4-28 of pregnancy and were evaluated for relaxin using guinea pig anti-porcine relaxin serum and avidin-biotin light microscopy immunohistochemistry. Results were identical for both models. Blastocysts first attach to the antimesometrial uterine surface by Day 7 post-copulation. Implantation on the mesometrial surface occurs on Days 8-11. Relaxin was observed in antimesometrial endometrial glands of both conceptus and non-conceptus-bearing uteri on Days 4-7 of pregnancy. Beyond Day 7, relaxin was observed in antimesometrial and mesometrial endometrial glandular and luminal epithelial cells at implantation sites of the conceptus-bearing uterus only. Relaxin was not found between implantation sites. Endometrial epithelial cells of the non-conceptus-bearing uterus were regressing by Day 9. These data indicate a conceptus-mediated maintenance of endometrial epithelial cells. Furthermore, the data suggest a paracrine maintenance of epithelial cell integrity and relaxin synthesis since these parameters are preserved only in the conceptus-bearing uterus. Cell-cell communication between conceptus and endometrium appears to be specific since endometrium between implantation sites does not contain relaxin. Uterine tissue from pseudopregnant rabbits (Days 1-16) was evaluated. Relaxin was observed in the antimesometrial glands on Day 7 only. Like the endometrium in the ligation model, endometrial epithelial cells of the pseudopregnant rabbit uterus were regressing by Day 9. These results indicate that pregnancy is not required for, but may enhance, relaxin synthesis. In addition, endometrial epithelial cells regress in the absence of pregnancy. Regression of endometrial epithelial cells on Day 9 suggests that maternal recognition of pregnancy occurs during the preimplantation period (Days 4-8).
Animals↗
Rabbit relaxin: the influence of pregnancy and ovariectomy during pregnancy on the plasma profile.
A porcine relaxin radioimmunoassay was developed to evaluate the profile of immunoreactive relaxin in rabbit plasma. Relaxin was nondetectable in pseudopregnant (Days 1, 4, 5-8, 12, and 16), nonpregnant, and male rabbits. However, in pregnant rabbits, relaxin was detected during the peri-implantation period (Days 4-9). Peak concentrations were reached on Day 15 and were maintained until parturition (Day 32). Relaxin concentrations abruptly decreased on Day 1 postpartum to low but detectable concentrations that were unchanged during the first week postpartum. In contrast, progesterone concentrations peaked earlier (Day 13), decreased after Day 25, and were not detectable on Day 1 postpartum. The effect of ovariectomy on the profile of plasma relaxin was evaluated. Four pregnant rabbits were ovariectomized (Day 13) and treated with medroxyprogesterone acetate to maintain pregnancy. As in normal pregnant rabbits, relaxin was observed initially during the peri-implantation period (Days 4-9) and increased to peak concentrations by Day 16. These concentrations were maintained until parturition and abruptly decreased on Day 1 postpartum to low yet detectable concentrations during the first week postpartum. The concentrations of relaxin in the plasma of ovariectomized medroxyprogesterone-treated rabbits were not different from those in three sham controls. These results indicate that the ovary is not a significant source of relaxin in pregnant rabbits. The unique observation of the presence of relaxin during the peri-implantation period suggests that this hormone has a role in preparing the rabbit uterus for implantation. The continued presence of relaxin during the first week postpartum may represent residual hormone, or it may suggest a physiological role during the early postpartum period.
Animals↗
Monoclonal antibodies specific for rat relaxin. V. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts development of the mammary apparatus and, hence, lactational performance in rats.
There were two related objectives to this study. The first was to determine the influence of relaxin on development of the mammary apparatus (nipples and glands) during the second half of pregnancy. The second was to determine whether the relaxin-dependent development of the mammary apparatus was required for normal postpartum lactational performance. Both objectives were accomplished by neutralizing endogenous relaxin throughout the second half of pregnancy with a monoclonal antibody specific for rat relaxin (MCA1). MCA1 was administered iv to rats daily from days 12-22 of pregnancy. On day 22 the morphology of the mammary apparatus of MCA1-treated rats differed from that of controls; nipples were dramatically smaller, collagen fibers had significantly greater mean density and consistency, and elastin fibers had greater mean density, length, and interdigitation. In addition, the mean number of alveoli surrounding lactiferous ducts was significantly smaller in MCA1-treated rats than in controls. There were no differences between MCA1-treated rats and controls in the mean thickness of connective tissue surrounding ducts, the height or density of luminal cells lining lactiferous ducts, or the sizes of either adipocytes or arteries. To examine lactational performance, MCA1-treated and control rats were cesarean sectioned between 2100-2400 h on day 22 of pregnancy and given foster pups born of untreated intact donors. Although both MCA1-treated rats and control rats exhibited a high incidence of maternal behavior after cesarean delivery, mean pup weight and incidence of live pups declined markedly during days 1-5 of fosterage in MCA1-treated rats compared to controls. Furthermore, unlike controls, there was no observable postpartum nipple development in MCA1-treated rats by day 5 of fosterage. Mammary glands obtained from MCA1-treated rats on day 5 of fosterage had markedly lower mean weight than controls. This study demonstrates that passive immunization of endogenous relaxin throughout the second half of pregnancy disrupts development of the nipples and mammary glands in the rat. Moreover, it establishes that relaxin's effects on the development of the mammary apparatus during pregnancy are essential for growth and survival of the young during lactation.
Animals↗