Extracellular acidosis enhances Zika virus infection both in human cells and ex-vivo tissue cultures from female reproductive tract.

Zika virus (ZIKV) is a flavivirus transmitted by mosquitoes of the genus Aedes, but unlike other flaviviruses, ZIKV can be sexually transmitted by vaginal intercourse. The healthy vaginal pH ranges from 4.0 to 6.0, reaching values of 6.0-7.0 after semen deposition. Here, we report that low extracellular pH values (range 6.2-6.6) dramatically increase ZIKV infection on cell lines of different origin including some derived from the female genital tract and monocyte-derived macrophages. Furthermore, low pH significantly increased ZIKV infection of human ectocervix and endocervix cultured ex-vivo. Enhancement of infection by low pH was also observed using different ZIKV strains and distinct methods to evaluate viral infection, i.e. plaque assays, RT-PCR, flow cytometry, and fluorescence microscopy. Analysis of the mechanisms involved revealed that the enhancement of ZIKV infection induced by low pH was associated with increased binding of the viral particles to the heparan sulphate expressed on the target cell surface. Acidosis represents a critical but generally overlooked feature of the female genital tract, with major implications for sexual transmission diseases. Our results suggest that low vaginal pH might promote male-to-female transmission of ZIKV infection.

Collagen, glycosaminoglycans and matrix metalloproteinase-2 and metalloproteinase-9 in the cervix of the ewe during prepubertal development.

The tortuous nature of the ovine cervix restricts the transcervical passage of the cannula, and many studies have aimed to understand the endocrine mechanism of the remodelling of cervical tissue in adult ewe. However, little is known about the remodelling of the cervical tissue during the prepubertal development of the lambs. To obtain histochemical and biochemical evidence about the nature of the prepubertal development of the cervix of the ewe, cervices of Corriedale lambs obtained at 0, 1, 2, 4, 6 and 8 months of age (n = 5 to 6 in each) were processed. Neutral and acidic glycosaminoglycans (by PAS-Alcian stain) were weakly in the cervical stroma and not shown change during the development, whereas the percentage volume of fibrillar collagen (by van Gieson stain) increases throughout the experimental period in the superficial fold stroma and deep wall stroma (p < 0.05). The relative cervical weight (g/kg of body weight) and the collagen concentration (by spectrophotometry, mg/mg wet tissue) showed an early decreasing phase from months 0 to 4 and a later increasing phase from months 4 to 8 (p < 0.05). The latent form of matrix metalloproteinase-2 (MMP-2) detected by gelatin zymography (ng/mg protein) decreased from months 0 to 2 and increased from months 4 to 8, whereas the activated form decreased from months 0 to 2, remained low until month 6 and then recovered on month 8 (p < 0.0001). Data suggest that the relative cervical weight biphasic pattern during the development is related to MMP-2-dependent changes in the collagen content.

Determination of carbofuran in surface water and biological tissue by sol-gel immunoaffinity extraction and on-line preconcentration/HPLC/UV analysis.

A selective and simple analytical method for the trace level determination of carbofuran in complex environmental and biological samples was developed based on immunoaffinity extraction (IAE) followed by on-line preconcentration and HPLC/UV analysis of the purified extract. The immunosorbent for IAE was prepared by sol-gel encapsulation of monoclonal anti-carbofuran antibodies, and was fully characterized for capacity, repeatability, binding strength, binding kinetics and cross-reactivity. Method performance was evaluated with two different types of difficult samples: dam water and methanolic extracts of epithelial cervical-uterine tissue. Linear behavior and quantitative recoveries were obtained from the analysis of samples spiked with carbofuran at 0.2-4 ng/mL (dam water, 50 mL samples) and 10-40 ng/mL (biological tissue extract, 2 mL samples). RSD (n=7) and detection limits were, respectively, 10.1% (spike 0.40 ng/mL) and 0.13 ng/mL for dam water; 8.5% (spike 20 ng/mL) and 5 ng/mL for the biological tissue extract. The excellent sample purification achieved with the IAE column allows precise and accurate determination of carbofuran in complex matrices, even when using non-selective UV detection in the chromatographic analysis.

Presence of HPV DNA in placenta and cervix of pregnant Mexican women.

PURPOSE: To identify the presence of HPV DNA in cervical as well as in placental tissue of pregnant Mexican women and to determine which type is more frequent. METHODS: In a cross-sectional study, 56 placental samples were obtained from 72 pregnant women. HPV DNA was extracted and amplified with polymerase chain reaction using a consensus primer and then identified by type using RsaI endonuclease. The main outcome measures were placenta with/without HPV relation and HPV types in placenta. RESULTS: HPV DNA was identified in 75% of cervical tissue samples and 47.2% of placental tissue samples. Type 18 was the most frequently identified HPV type. CONCLUSIONS: There was a higher frequency of HPV DNA found in the cervix of Mexican women during pregnancy than reported in the previous studies. Its identification in full-term placental tissue has no relation to the type of delivery in childbirth.

Immunohistochemical expression of granzyme B and vascular endothelial growth factor (VEGF) in normal uterine cervices and low and high grade squamous intraepithelial lesions.

PURPOSE: This study aimed to evaluate the immunoexpression of granzyme B and vascular endothelial growth factor (VEGF) in the variants of cervical squamous intraepithelial neoplasia. METHODS: Granzyme B immunohistochemical expression was studied in the epithelium, stroma and in both the epithelium + stroma of 142 fragments of uterine cervix; there were 34 grade 1 cervical intraepithelial neoplasias (CIN 1), 36 grade 2 cervical intraepithelial neoplasias (CIN 2), 33 grade 3 cervical intraepithelial neoplasias (CIN 3) and 39 uterine cervix fragments without abnormalities - control group. Immunoexpression of VEGF was studied in 160 uterine cervix fragments, with 43 grade 1 cervical intraepithelial neoplasias (CIN 1), 33 grade 2 cervical intraepithelial neoplasias (CIN 2), 31 grade 3 cervical intraepithelial neoplasias (CIN 3) and 53 uterine cervix fragments without abnormalities--control group. RESULTS: In the stroma, immunoexpression of granzyme B in grade 1 cervical intraepithelial neoplasias was smaller than in grade 3 cervical intraepithelial neoplasias. High VEGF immunoexpression was found in grade 3 cervical intraepithelial neoplasias while it was low in grade 1 cervical intraepithelial neoplasias and in the control group. CONCLUSION: The higher the severity of the cervical intraepithelial lesion, the higher the immunoexpression of granzyme B. A progressive increase in VEGF immunoexpression was found in the intense grade, according to the severity of the cervical intraepithelial neoplasia.

Glycosaminoglycan distribution in the rat uterine cervix during the estrous cycle.

OBJECTIVE: To analyze the amount of glycosaminoglycans in the uterine cervix during each phase of the rat estrous cycle. DESIGN: Based on vaginal smears, forty female, regularly cycling rats were divided into four groups (n = 10 for each group): GI - proestrous, GII - estrous, GIII - metaestrous and GIV - diestrous. Animals were sacrificed at each phase of the cycle, and the cervix was immediately removed and submitted to biochemical extraction and determination of sulfated glycosaminoglycans and hyaluronic acid. The results were analyzed by ANOVA followed by the Bonferroni post-hoc test. RESULTS: The uterine cervix had the highest amount of total sulfated glycosaminoglycans and dermatan sulfate during the estrous phase (8.90 +/- 0.55 mg/g of cetonic extract, p<0.001; and 8.86 +/- 0.57 mg/g of cetonic extract, p<0.001). In addition, there was more heparan sulfate at the cervix during the proestrous phase (0.185 +/- 0.03 mg/g of cetonic extract) than during any other phase (p<0.001). There were no significant changes in the concentration of hyaluronic acid in the uterine cervix during the estrous cycle. CONCLUSION: Our data suggest that the amount of total sulfated glycosaminoglycans may be influenced by hormonal fluctuations related to the estrous cycle, with dermatan sulfate and heparan sulfate being the glycosaminoglycans most sensitive to hormonal change.

Glycosaminoglycan distribution in the rat uterine cervix during the estrous cycle

OBJECTIVE: To analyze the amount of glycosaminoglycans in the uterine cervix during each phase of the rat estrous cycle. DESIGN: Based on vaginal smears, forty female, regularly cycling rats were divided into four groups (n = 10 for each group): GI - proestrous, GII - estrous, GIII - metaestrous and GIV - diestrous. Animals were sacrificed at each phase of the cycle, and the cervix was immediately removed and submitted to biochemical extraction and determination of sulfated glycosaminoglycans and hyaluronic acid. The results were analyzed by ANOVA followed by the Bonferroni post-hoc test. RESULTS: The uterine cervix had the highest amount of total sulfated glycosaminoglycans and dermatan sulfate during the estrous phase (8.90 ± 0.55 mg/g of cetonic extract, p<0.001; and 8.86 ± 0.57 mg/g of cetonic extract, p<0.001). In addition, there was more heparan sulfate at the cervix during the proestrous phase (0.185 ± 0.03 mg/g of cetonic extract) than during any other phase (p<0.001). There were no significant changes in the concentration of hyaluronic acid in the uterine cervix during the estrous cycle. CONCLUSION: Our data suggest that the amount of total sulfated glycosaminoglycans may be influenced by hormonal fluctuations related to the estrous cycle, with dermatan sulfate and heparan sulfate being the glycosaminoglycans most sensitive to hormonal change.

Immunohistochemical expression of ubiquitin and telomerase in cervical cancer.

Ubiquitin and telomerase immunohistochemical expression patterns in cervical cancer were compared with normal cervical tissue samples. Eighty-one cervical cancer cases and 22 normal exo-endocervical tissue were examined with polyclonal antibody for ubiquitin and 44G12 clone for telomerase using tissue microarrays. The results were interpreted using a semiquantitative scale The average age of patients was 50.67 years. The most frequent histological types were moderately differentiated epidermoid carcinoma (43.5%), according to the degree of differentiation, and endocervical adenocarcinoma (42.1%). Immunohistochemical findings were as follows: 98.7% of cervical cancers showed immunoexpression for ubiquitin and 52.6% for telomerase. Statistically significant differences were found in tumor immunoreactivity when compared with control tissue (p < 0.0007) for both biomarkers. There was no significant difference in biomarker expression at different histological types of tumors, although telomerase was less expressed in endocervical adenocarcinoma. Our findings confirm that abnormal immunoexpression pattern of ubiquitin and telomerase is common in HPV-positive cervical cancer, indicating the existence of an intense degradation of proteins, subsequent cellular immortalization and maintenance of the malignant phenotype.

[Histochemical changes of the glycosaminoglycans in the uterine cervix of pregnant rats after local injection of hyaluronidase]. / Alterações histoquímicas das glicosaminoglicanas na cérvice uterina no final da prenhez da rata albina após ministração local de hialuronidase.

PURPOSE: to study the histochemical changes related to the uterine cervix glycosaminoglycan of the albino female rat, after local administration of hyaluronidases at the end of pregnancy. METHODS: ten female rats with positive pregnancy tests were randomly distributed in two numerically equal groups. The control group (Cg) was built up with rats that received a single dose of 1 mL of distilled water in the uterine cervix, under anesthesia, at the 18th pregnancy day. In the experimental group (Exg), the rats received 0.02 mL of hyaluronidase, diluted in 0.98 mL of distilled water (1 mL as a total), under the same conditions as the Cg. At the 20th pregnancy day, the rats were anesthetized once again and submitted to dissection, and the cervix prepared for histochemical study with alcian blue dye and its blockades (pH=0.5, pH=2.5, methylation and saponification). RESULTS: strongly positive reaction in the lamina propria (+3) has been seen in the Cg, and negative reaction in the Exg, with pH=0.5 alcian blue staining. With pH=2.5, staining has also been strongly positive (+4) in the Cg, and weakly positive (+1) in the Exg slide. After methylation, both groups have shown negative reaction, with pH=2.5 alcian blue staining. The lamina propria staining became negative after methylation in both groups, followed by saponification and enzymatic digestion on slide. CONCLUSIONS: there is clear predominance of sulphated glycosaminoglycans in the Cg as compared to the Exg and a small amount of identified carboxylated glycosaminoglycans in the Exg. The changes evidenced in the extracellular matrix have suggested that the hyaluronidase injected in the uterine cervix has promoted biochemical changes compatible with cervix maturation.

Relation between vaginal and endocervical pH in patients undergoing cold-knife conization and hysterectomy.

OBJECTIVE: This study aimed to investigate the influence of endocervical pH on vaginal pH, and also the changes in these pH values following hysterectomy and cold-knife conization. Vaginal pH is important for maintaining the equilibrium of the vaginal microflora. PATIENTS AND METHODS: Two groups of women were studied: the first (n = 20, median age 45, range 33-50 years-old), before and after hysterectomy (without ovariectomy) for myomatosis; the second group (n = 18, median age 38.5, range 37-65 years-old), before and after cold-knife conization for cervical intraepithelial neoplasia (CIN) grade II or III. Four samples (before and 90 days after surgery) were collected from the women by means of swabs: (1) anterior vaginal fornix, (2) posterior vaginal fornix, (3) posterior wall of lower vagina, and (4) endocervix (except in cases after hysterectomy). The pH was measured using a digital pHmeter (Sentron). RESULTS: We observed that endocervical pH was less acidic than were all the vaginal locations measured, before both surgeries. After both surgeries, all vaginal pH measurements were higher, but without reaching statistical significance. Endocervical pH correlated with vaginal pH. CONCLUSIONS: We concluded that recent hysterectomy does not alter vaginal pH and that vaginal and endocervical pH values are related.

Immunohistochemical expression of p16(INK4A) in normal uterine cervix, nonneoplastic epithelial lesions, and low-grade squamous intraepithelial lesions.

OBJECTIVES: In this study, the authors analyzed the immunoexpression of p16 in high-risk human papillomavirus DNA-negative normal and nonneoplastic cervical epithelia, in low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, and squamous cell carcinoma. MATERIALS AND METHODS: A retrospective study, in which 58 normal cervical hysterectomy samples, 56 nonneoplastic cervical biopsies, 88 CIN 1, 33 CIN 2, 32 CIN 3, and 47 invasive squamous cell carcinoma biopsies, were evaluated for p16 immunoexpression. Human papillomavirus tests were also performed. RESULTS: p16 immunohistochemistry seems to reveal possible different biological subgroups of lesions among morphologically similar mildly dysplastic cervical epithelia. CONCLUSION: Distribution patterns of p16 protein might be useful to predict different outcomes in CIN 1.

Relation between vaginal and endocervical pH in pre- and post-menopausal women.

We aimed to verify whether vaginal fornix pH is related to endocervical pH and whether or not acid pH could contribute to the prophylactic treatment of vaginal infections. Four groups of healthy women with or without uterus were selected: pre-menopausal (>39 years) and post-menopausal (<61 years). Pre-menopausal non-hysterectomized women were further analysed in proliferative (8-12 days) and secretory phase (18-22 days) of the menstrual cycle. Endocervical and vaginal pH was determined by a digitally pH metro during the gynaecological examination. Vaginal pH is more acid than endocervical pH in pre- and post-menopausal women, 5.1 versus 6 and 5.4 versus 6.4 (P<0.001), respectively. Vaginal pH is related to endocervical pH in proliferative phase of menstrual cycle and post-menopausal women (P=0.009). Pre- and post-menopausal hysterectomized women presented more acid vaginal pH than non-hysterectomized women, 4.35 versus 5.1 and 4.9 versus 5.4 (P<0.05), respectively. Endocervical pH has not presented change during menstrual cycle and menopause, 6 and 6.4, respectively. Vaginal pH is related to endocervical pH in proliferative phase of menstrual cycle phase and post-menopausal women.

Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes.

OBJECTIVE: The purpose of this study was to examine the diagnostic performance of ultrasonographic measurement of the cervical length and vaginal fetal fibronectin determination in the prediction of preterm delivery in patients with preterm uterine contractions and intact membranes. STUDY DESIGN: Ultrasound examination of the cervical length and fetal fibronectin determination in vaginal secretions were performed in 215 patients admitted with preterm uterine contractions (22-35 weeks) and cervical dilatation of

Estrogen and progesterone receptors in human papilloma virus-related cervical neoplasia.

Estrogen (ER) and progesterone (PR) receptors in the normal uterine cervix, cervical intraepithelial neoplasia and invasive carcinoma were studied in consecutive samples from Hospital do Cáncer, São Paulo, between 1996 and 1997. Tissue was collected by removing a fragment of the tumoral area using a 5-mm diameter biopsy punch, followed by removal of a macroscopically normal area as close as possible from the tumor. Histopathological confirmation was obtained for all specimens analyzed. A total of 24 normal tissues, 17 cases of cervical intraepithelial neoplasia and 7 of invasive carcinomas were studied. The ER/PR ratio was determined by immunohistochemistry using monoclonal antibodies specific for each receptor. Adjacent tissue slides were submitted to generic PCR for human papillomavirus (HPV) DNA detection followed by typing by dot blot hybridization. About half (45.8%) of the tumors were HPV DNA positive while 29.1% of the patients were also HPV positive in their respective normal tissue. ER was negative in the tumoral epithelium of 11 HPV-positive patients (P=0.04). There was a trend in the ER distribution in normal tissue that was opposite to that from lesions, but it was not statistically significant (P=0.069). No difference in ER distribution in stromal tissues was observed between HPV-positive and HPV-negative tissues. PR staining was negative in the epithelium of all cases studied. The results obtained from this small number of cases cannot be considered to be conclusive but do suggest that factors related to viral infection affect the expression of these ER/PR cervix receptors.

Collagen remodelling in the guinea-pig uterine cervix at term is associated with a decrease in progesterone receptor expression.

In human and guinea-pig parturition, progesterone withdrawal and estrogen action are not mediated by changes in their circulating levels. Instead, these events might be promoted by changes in the responsiveness of the uterus and cervix to progesterone and estrogen via changes in their receptors. In this study, the guinea-pig model was used to investigate whether high levels of progesterone and estrogen at term are associated with regional changes in PR and ERalpha levels in uterus and cervix. PR and ERalpha profiles were established in both subepithelium and the muscular layer of the cervix and the lower uterine horns during pregnancy, parturition and postpartum; while collagen remodelling was measured in the subepithelium. Our data showed that collagen remodelling involved in cervical ripening is temporally and spatially associated with a decrease in PR, whereas high expression of ERalpha is observed. This association was found in the subepithelium of the cervical tissue but not in the same region of the uterus. The muscular region of the cervix and uterus also present a transiently decreased expression of PR while ERalpha levels remain high. Thus, the present results indicate that, before parturition, diminished responsiveness of the cervix to progesterone might be caused by a decrease in PR levels and that this may be the mechanism of functional progesterone withdrawal. The guinea-pig was further validated as an animal model for human parturition studies.

Cellular turnover in the rat uterine cervix and its relationship to estrogen and progesterone receptor dynamics.

Histoarchitectural changes of the uterine cervix allow its successful adaptation to different physiological conditions. In this study, we evaluated cell turnover in each cellular compartment of the uterine cervix in association with steroid hormone receptor expression in order to establish the range of physiological changes. Proliferation, apoptosis, and progesterone receptor (PR) and estrogen receptor alpha (ERalpha) expression were evaluated in cycling, pregnant, and postpartum rats. In estrus and diestrus II, ERalpha and PR expression exhibited variations according to the region evaluated. Proliferation and apoptosis showed a reciprocal pattern, the epithelium being the region with higher cell turnover. High apoptotic index (AI) in estrus was associated with the lowest ERalpha and the highest PR scores. During pregnancy, proliferation of the epithelium was the predominant event and AI was low. On Postpartum Day 1 (PPD1), proliferation decreased while apoptosis increased. As described for the estrous cycle, during pregnancy and PPD1, AI and ERalpha were negatively correlated. In the fibroblastic stroma, low proliferation was observed throughout pregnancy; however, there was a net increase in cell number because very few cells underwent apoptosis. No difference in ERalpha was observed in fibroblastic cells during pregnancy and postpartum; however, a great decrease of this receptor in the epithelial compartment was observed after delivery. Unlike cervical epithelium, PR was highly expressed in stromal cells. At term, a dramatic increase in epithelial PR was observed. While epithelial PR remained high on PPD1, a decrease was observed in muscle stroma. These results show that, in all stages studied, 1) ERalpha and PR have different patterns of expression with differential responses to signals that modulate proliferation and/or apoptosis depending on the cellular compartment, and 2) even though the epithelium is the region with the highest cell turnover, the fibroblastic and muscle stroma are active regions that have their own patterns of behavior.

Changes in retinoblastoma gene expression during cervical cancer progression.

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.

Presence of proliferating (MiB-1-positive) cells in cervical smears of women infected with HIV is associated with clinical outcome: a study of Brazilian women.

The hypothesis tested was that there is an association between the presence of proliferating (MiB-1-positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV-positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV- women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB-1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB-1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB-1-positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient.

Expression of Ki-67 in cervical epithelial cells in preneoplastic lesions of patients with AIDS.

The objective of the present investigation was to study the expression of the proliferation marker Ki-67 in cervical intraepithelial lesions in women with AIDS. We studied 18 low-grade cervical intraepithelial lesions (Lo-CIN) and 8 high-grade cervical intraepithelial lesions (Hi-CIN ) in AIDS patients and 18 Lo-CIN and 14 Hi-CIN in patients from the general population. Positive Ki-67 nuclei were counted. A significantly higher number of Ki-67-positive cells (p < 0.001) was found in Lo-CIN of AIDS patients (mean 29.18 +/- 10.44) as compared with Lo-CIN of general-population women (mean 17.08 +/- 7.40), whereas no significant difference in positive Ki-67 nuclei was observed in the Hi-CIN of AIDS patients and of patients from the general population (p > 0.05). We conclude that the proliferative potential of cervical cells in Lo-CIN - as studied by the expression of the proliferation marker Ki-67 - is higher in AIDS patients than in the general population.

Estrogen and progesterone receptors in the ovine cervix during the postpartum period.

Cervical estrogen (E) and progesterone (P) receptors were characterized and quantified during the postpartum period in Corriedale ewes lambing in the late breeding season. Cervices and uteri were collected after ovariohysterectomy at 1 d (n = 2), 5 d (n = 4), 17 d (n = 2) or 30 d (n = 2) post partum. The estrogen and progesterone receptors were measured using binding assays with tritiated hormones, dextran charcoal separation and inverse Scatchard analysis. Similar kinetic parameters in cytosolic binding sites for both hormones were found in all cervical and uterine samples, indicating that the binding protein in both tissues is of the same nature. Receptor concentrations (fmol/mg cytosolic protein) in the cervix of early (1 to 5 d, n = 6) and late (17 to 30 d, n = 4) postpartum ewes were 348 +/- 66 vs 994 +/- 145 (P < 0.05) for E and 618 +/- 126 vs 1170 +/- 201 (P < 0.05) for P, respectively. These data suggest an increased synthesis of receptors, probably due to the presence of ovarian estrogen-active follicles. Cervical E and P receptor concentrations were similar or higher than those in the uterus (1.40 +/- 0.15, n = 10 and 1.51 +/- 0.19, n = 10; for E and P respectively), and these receptor ratios did not differ between the early and late postpartum period. The high ratio between cervical/uterine receptors suggests that the ovine cervix may be a very sensitive to steroid action. In conclusion, it was shown that restoration of steroid receptors during the postpartum period in the ovine cervix is similar to receptor dynamics in the uterus, and is probably associated with the recovery of ovarian cyclicity.