Postpartum Involution Research Articles

The morphofunctional pattern of neuronal biogenic amines in postpartum involution period-an in vivo study.

Postpartum uterine diseases are associated with significant imbalance in the levels of biogenic amines (BAs) in rat uterus. Mast cells (MCs) are the main suppliers of BAs such as serotonin, catecholamines, and histamine in uterus. There is limited evidence of the BA-positive elements involved in the physiological regulation of uterus during postpartum involution. The aim of present study is to determine the concentration and distribution of biogenic amines (BAs) such as histamine, serotonin, and catecholamines in the uterine endometrium, myometrium, and peritoneal fluid (PF) during the postpartum uterine involution. A total of 110 nulliparous outbred female nonpregnant Wistar rats of mature age were divided into eleven groups (n=10 per group) according to days of postpartum involution. Tissue specimens of uterine segments, PF were prepared. Serotonin, catecholamines, and histamine concentrations were examined by fluorescence-histochemical techniques. The fluorescence of the BA-positive elements was detected and analyzed by microspectrofluorimetry. Results were analyzed using the Kruskal-Wallis chi-squared test and pairwise Mann-Whitney-Wilcoxon tests with "Benjamini-Hochberg correction" in R 3.6.3. Mast cells in uterine segments, PF exhibited characteristic yellowish-green fluorescence. The highest MCs number was reported in corpus uteri on the 15th day of postpartum involution. Serotonin, catecholamines, and histamine levels were significantly higher in BA-positive elements in the initial days. BA content was dynamic and relies on the time elapsed after parturition. There was statistically significant difference in the levels of BAs in the cornu and cervix uteri. A single morphofunctional complex of BA supply was noticed in the reproductive system of the rats. The coupled interactions of intra- and extra-organic BA-positive elements was associated with anabolic/catabolic equilibrium in uterus through the metabolism of serotonin, catecholamines, and histamine during postpartum involution.

Vitamin D as a Potential Preventive Agent For Young Women's Breast Cancer.

Clinical studies backed by research in animal models suggest that vitamin D may protect against the development of breast cancer, implicating vitamin D as a promising candidate for breast cancer prevention. However, despite clear preclinical evidence showing protective roles for vitamin D, broadly targeted clinical trials of vitamin D supplementation have yielded conflicting findings, highlighting the complexity of translating preclinical data to efficacy in humans. While vitamin D supplementation targeted to high-risk populations is a strategy anticipated to increase prevention efficacy, a complimentary approach is to target transient, developmental windows of elevated breast cancer risk. Postpartum mammary gland involution represents a developmental window of increased breast cancer promotion that may be poised for vitamin D supplementation. Targeting the window of involution with short-term vitamin D intervention may offer a simple, cost-effective approach for the prevention of breast cancers that develop postpartum. In this review, we highlight epidemiologic and preclinical studies linking vitamin D deficiency with breast cancer development. We discuss the underlying mechanisms through which vitamin D deficiency contributes to cancer development, with an emphasis on the anti-inflammatory activity of vitamin D. We also discuss current evidence for vitamin D as an immunotherapeutic agent and the potential for vitamin D as a preventative strategy for young woman's breast cancer.

The Role of Neurogenic Bioamines in Nerve Fibers of Uterus during the Postpartum Involution in Experimental Animal Models.

Biogenic amines (BAs) secreted by the sympathetic neural apparatus of rat uterus are reported to be conducive to the uterine functional activity during postpartum involution; the imbalance in BAs ratio could confer postpartum reproductive disorders including improper postpartum involution. The objective of this study is to identify the changes in the density of uterine sympathetic nerves implicated in the pathology of endometriosis, adenomyosis, and delayed uterine involution. The present study aims to ascertain 'serotonin' and 'catecholamine' concentrations in mesenteric mast cells (MCs), and structural elements of nerve fibers across the perivascular plexuses (PPs) and single sympathetic nerve terminals (SST). Furthermore, the density of their spatial distribution (SDP and SDT) in the uterine body, cervix, and mesometrium was determined during postpartum involution. Tissue specimens of postpartum uterus were obtained from 55 nulliparous female Wistar outbred strain rats, which were grouped according to the days after parturition at the time of sacrifice. The nerve fibers of PP and SST exhibited emerald green fluorescence, which was detected by glyoxylic acid fluorescence technique; the fluorescence invoked by BAs was identified by microspectrofluorimetry. Concentrations of BAs were extensive in the varicosities of PP and SST on the 10th day. However, the highest BA concentrations were found in structural elements of PP in the uterine mesometrium in the initial days of postpartum. In mesenteric MC, serotonin and catecholamines were at the highest concentration on the 10th day of postpartum. Histamines peaked on the 6th day. SDP and SDT were increased significantly in all structural elements of uterine nerve fibers in the uterine body and cervix compared to SDP in mesentery. Considering that catecholamines and serotonin are antagonists in many aspects of their biological action, the ratio of BAs should be well-balanced to maintain anabolic- catabolic equilibrium in the rat uterus.

Postpartum Uterine Involution and Embryonic Development Pattern in Chinese Holstein Dairy Cows.

Understanding the postpartum uterine involution pattern and embryonic development could facilitate bovine reproduction management, improve reproductive efficiency, and diagnosis of the reproductive disorder, which would contribute to the success of the dairy business. This study aimed to investigate postpartum uterine involution and embryonic developmental patterns or postconceptional marks of embryonic fetal development in Chinese Holstein dairy cows using B-mode ultrasonography. The results revealed a significant decline in the involution period with an increase of parity and age. The uterine involution period was shorter in multiparous cows when compared with cows with lower parities. Consistently, cows over 4 years old recovered faster than younger cows (2 or 3 years). Besides, the elder cows (over 4 years) had a relatively larger size of resumed cervix uteri and horns. Postpartum uterine involution pattern analysis revealed that the reproductive tract recovered very fast during the first 16 days postpartum for all the parity. Results of postconceptional marks of embryo development revealed a slow increase in diameter of the gravid uterine horn and crown-rump length (CRL) before day 60. In contrast, this increase was dramatic and rapid after the 60th day. We also established two models to estimate gestational age based on gravid uterine horn diameter or CRL. A formula was established to determine the gravid uterine horn size during postconceptional on day 30th–day 90th (r = 0.8714, P < 0.01). In addition, a significant positive correlation between CRL and gestational age (r = 0.98151, P < 0.01) was built. In conclusion, these results illustrated that parity and calving age had significant effects on uterine involution in Chinese Holstein cows. Crown-rump length and gravid uterine horn diameter are both efficient for evaluating the embryo growth. These current findings broaden the understanding of basic reproductive pattern in Chinese Holstein cows and could benefit bovine reproductive management primarily in postpartum and early pregnant cows to reduce the calving interval and avoid periparturient metabolic diseases.

Postpartum uterine involution and ovarian follicular dynamics in crossbreed Anatolian water buffalo (Bubalus bubalis) during summer season

It was aimed to monitor postpartum (pp) uterine involution and follicular wave pattern by transrectal ultrasonography and detection of concentrations of milk progesterone (P4) in eleven water buffaloes during the summer season in Turkey. The data obtained from the first day of calving to positive pregnancy diagnosis were evaluated on a daily basis. Uterine position scores and nonechogenic material showed a decreasing grade pattern related to the time (P < 0.0001). A time effect was evident with uterine horn thickness (P < 0.05) or intercaruncular zone thickness (P < 0.01) and uterine horn lumen (P < 0.01). Uterine horn thickness showed a gravidity x time interaction (P < 0.05). Gravidity x time interaction was not evident in total uterine horn thickness but time effect was seen (P < 0.0001). Time effect was also evident for the thickness of uterine body (P < 0.0001) and cervix uteri (P < 0.01). The uterine body and horns were returned to previously nongravid state on day 26.00 ± 2.38 and the interval from calving to complete disappearance of uterine fluid was accomplished on day 31.44 ± 3.23 pp. The previously gravid and nongravid uterine horns, uterine body and cervix uteri involuted on day 31.42 ± 1.39, 28.37 ± 0.65, 29.37 ± 0.73 and 27.87 ± 0.47 pp, respectively. The interval from calving to first observation of dominant follicle of nonovulatory wave was 18.54 ± 6.91 days and on average 3.45 ± 1.91 nonovulatory waves were observed. Postpartum first ovulation occurred on day 64.45 ± 18.49. One and two wave models or combination of both waves were observed. The interval from calving to pregnancy was 72.36 ± 21.33 days. The maximum concentrations of milk P$_{4}$ during short or normal cycles and pregnancy were 0.62 ng/mL, 2.2 ng/mL, and 4.04 ng/mL, respectively. In conclusion, the presence of one or two waves should be considered when estrous synchronization programmes are planned in Anatolian water buffaloes during summer season.

Optimization methods for correcting the duration of the anovulatory period of cattle

Post-calving anestrus leads to serious economic losses and is the reason for the animal culling. Deficiency of estrogen and hypofunctional state of the ovaries due to negative energy balance, as well as violations of the timing of postpartum involution of the uterus are considered the leading causes of an extended anovulatory period in fresh cows. A comparison was made of the therapeutic efficacy of Ovsynch scheme and Ovariovit preparation when used in first heifers with post-calving anestrus against the background of ovarian hypofunction. When using Ovsynch scheme, the fertility of the first insemination was 50%; estrous cyclicity recovered in 80% of first heifers. When using Ovariovit, the fertility of the first insemination was 60%; the estrous cycle was restored in 100% of first heifers.

Postpartum Uterine Ultrasonographic Scale: a novel method to standardize the assessment of uterine postpartum involution.

Postpartum hemorrhage is a leading cause of maternal mortality. Various methods can be used to evaluate the postpartum uterine cavity volume. This work aims to introduce a simple method for uterine postpartum cavity volume evaluation, called Postpartum Uterine Ultrasonographic Scale (PUUS), which could be used routinely. In this prospective study, 131 consecutive Caucasian patients were evaluated by using the PUUS method. The mean age was 27.72 years (ranging from 15 to 42). Patients were examined in the same time intervals: within the first 24-48 hours after delivery in case of vaginal delivery, and within the first 48-72 hours, in case of cesarean delivery. Patients with PUUS grades 2, 3, or 4 were reexamined daily until the PUUS grade declined to 1 or 0. The PUUS method evaluated the length of the endometrium of the uterine cavity occupied by blood or debris, from grade 0 (no blood) to grade 4 (over three-quarters of the endometrial length occupied by blood/debris). The PUUS grade of uterine involution varied with the day of examination, gestation, and parity. In this article, a novel method of evaluating uterine postpartum involution titled PUUS is introduced. This method standardized uterine cavity involution in a numerical fashion. We hope that the PUUS scale could further be used to decrease the morbidity and mortality of women due to postpartum hemorrhage.

Hydrastinine with uterine bleeding.

Analyzing the pharmaceutical treatment of uterine bleeding, the author quite rightly stops at ergot preparations and hydrastis canadensis, as the most effective means. Ergot acts mainly on the very muscle of the uterus and, therefore, is shown in atonic bleeding, depending for example. from insufficient postpartum involution of the uterus, while hydrastis is most useful for so-called secondary bleeding that occurs under the influence of diseases of the uterine appendages, with chronic endometritis, in the menopausal period, in girls, etc. The disadvantage of this remedy, in the form of a liquid extract, is that it does not work well when used when bleeding has already occurred, and that to get the proper effect, it must be taken long (two weeks) before the expected Meno-or metrorrhagia.

The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning.

Insulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus on Pregnancy-Associated Plasma Protein A (PAPP-A), a protease involved in the degradation of IGFBP-5. PAPP-A is overexpressed in the majority of breast cancers but its role in cancer has only begun to be explored. More specifically, this review aims at highlighting the role of post-partum involution in the oncogenic function of PAPP-A. Notably, we summarize recent studies indicating that PAPP-A plays a role not only in the degradation of IGFBP-5 but also in the deposition of collagen and activation of the collagen receptor discoidin 2 (DDR2) during post-partum involution. Finally, considering the immunosuppressive microenvironment of post-partum involution, we also discuss the unexpected finding made in Ewing Sarcoma that PAPP-A plays a role in immune evasion. While the immunosuppressive role of PAPP-A in breast cancer remains to be determined, collectively these studies highlight the multifaced role of PAPP-A in cancer that extends well beyond its effect on IGF-signaling.

Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism.

There is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumor growth through neutrophils' activity. However, how estrogen and neutrophils influence mammary involution are unknown. Combined analysis of transcriptomic, protein, and immunohistochemical data in BALB/c mice showed that estrogen promotes involution by exacerbating inflammation, cell death and adipocytes repopulation. Remarkably, 88% of estrogen-regulated genes in mammary tissue were mediated through neutrophils, which were recruited through estrogen-induced CXCR2 signalling in an autocrine fashion. While neutrophils mediate estrogen-induced inflammation and adipocytes repopulation, estrogen-induced mammary cell death was via lysosome-mediated programmed cell death through upregulation of cathepsin B, Tnf and Bid in a neutrophil-independent manner. Notably, these multifaceted effects of estrogen are mostly mediated by ERα and unique to the phase of mammary involution. These findings are important for the development of intervention strategies for parity-associated breast cancer.

Postpartum Involution and Cancer: An Opportunity for Targeted Breast Cancer Prevention and Treatments?

Childbirth at any age confers a transient increased risk for breast cancer in the first decade postpartum and this window of adverse effect extends over two decades in women with late-age first childbirth (>35 years of age). Crossover to the protective effect of pregnancy is dependent on age at first pregnancy, with young mothers receiving the most benefit. Furthermore, breast cancer diagnosis during the 5- to 10-year postpartum window associates with high risk for subsequent metastatic disease. Notably, lactation has been shown to be protective against breast cancer incidence overall, with varying degrees of protection by race, multiparity, and lifetime duration of lactation. An effect for lactation on breast cancer outcome after diagnosis has not been described. We discuss the most recent data and mechanistic insights underlying these epidemiologic findings. Postpartum involution of the breast has been identified as a key mediator of the increased risk for metastasis in women diagnosed within 5-10 years of a completed pregnancy. During breast involution, immune avoidance, increased lymphatic network, extracellular matrix remodeling, and increased seeding to the liver and lymph node work as interconnected pathways, leading to the adverse effect of a postpartum diagnosis. We al discuss a novel mechanism underlying the protective effect of breastfeeding. Collectively, these mechanistic insights offer potential therapeutic avenues for the prevention and/or improved treatment of postpartum breast cancer.

The Effect of Mycobacterium Cell Wall Fraction on Histologic, Immunologic, and Clinical Parameters of Postpartum Involution in the Mare

Maintaining yearly foal production is important for the economic success of the broodmare, and this requires breeding to occur as quickly postpartum as possible. The initial postpartum estrus occurs within 5–20 days postpartum, whereas the uterus is still undergoing repair from tissue alterations during pregnancy and parturition, a process known as involution. Attempts have been made to hasten this process, but with minimal success. Mycobacterium cell wall fraction (MCWF) is an immunomodulator that has been shown to reduce bacterial growth and alter aspects of the immune response to breeding, but it is unknown if MCWF hastens the process of involution. Therefore, the objectives of this study were to (1) investigate the effect of MCWF on tissue remodeling, (2) assess the effect of MCWF on the local immune system of the uterus, and (3) determine the optimal treatment interval needed for these processes to occur. We hypothesize that repeated treatments of MCWF postpartum will hasten the process of involution. To study this, 16 pregnant mares of mixed breeds were evaluated postpartum. Control mares (n = 4) received 1.5 mL lactated Ringer’s solution intravenously on Day 1 (Day 0 = day of parturition) postpartum and again on Day 7, whereas treated mares either received 1.5 mL Settle intravenously on Day 1 and Day 7 (TX1; n = 6) or 1.5 mL Settle intravenously on Day 1 and then every 3 days until ovulation was detected (TX2; n = 6) and then evaluated until 15 days postpartum. Mares were assessed every 3 days for clinical, immunologic, and histologic parameters. Clinical parameters were assessed with transrectal ultrasonography and included ovarian activity, uterine fluid retention, and measurement of the uterine diameter, in addition to endometrial culture. Immunologic parameters included endometrial biopsies for quantitative polymerase chain reaction for expression of various cytokines (interleukin [IL]-1β, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor [TNF], interferon [IFN]-γ, and granulocyte-macrophage colony-stimulating factor) in addition to endometrial cytology. Formalin-fixed endometrial biopsies were histologically assessed for the retention of microcaruncles, dilation of endometrial glands, and inflammation of the mucosa, stratum compactum, and spongiosum. Statistics were performed using SAS 9.4, using a mixed model for repeated measures with mare and treatment as a random effect. All post-hoc analysis was done using a Tukey’s honestly significant difference test. Involution was considered complete by Day 15 postpartum in all mares, and the day postpartum had a significant effect on almost all parameters investigated, indicating the immunologic process of involution. Treatment with MCWF decreased the magnitude of bacterial growth in addition to time to negative culture. In addition, MCWF increased the expression of IL-1β, IFNγ, and TNF. Although minimal treatment effect was noted histologically, a decrease in mucosal inflammation was seen in MCWF-treated mares. In conclusion, involution appears to be influenced by the immune system. In addition, MCWF appears to have a bactericidal effect on the postpartum mare, and this may be because of an increase in proinflammatory cytokines. It is unknown if this bactericidal property will improve fertility on the first estrous cycle postpartum, and future studies are needed to determine this.

Consequence of Exogenous Administration of Oxytocin on Reproductive and Productive Parameters during Postpartum Involution Period in Newly Calved Nili-Ravi Buffaloes

Consequence of Exogenous Administration of Oxytocin on Reproductive and Productive Parameters during Postpartum Involution Period in Newly Calved Nili-Ravi Buffaloes

Postpartum involution of mouse myometrium under conditions of acute toxic hepatosis

The goal of the research was to study the structural processes of postpartum myometrial involution of C57Bl/6 mice in conditions of acute CCl4-induced hepatosis. The study was conducted on 60 female C57Bl/6 mice. Animals were divided into 2 groups: 1st – mice of the control group with physiological pregnancy, 2nd – pregnant mice with acute CCl4-induced hepatosis. The main mechanism of the process of postpartum involution of the myometrium of C57Bl/6 mice was clasmacytosis, that was morphologically represented by the presence of cytoplasmic conglomerates in the interstitium, and to a lesser extent myocyte apoptosis. More pronounced manifestations of the processes of involution were observed in the subserous muscle layer, smaller changes were observed in the vascular muscle layer and least of all in the subvascular (submucous) muscle layer. The myometrial involution processes in C57Bl/6 mice under conditions of acute CCl4-induced hepatosis slow down and do not end by the 10th day of the postpartum period, in contrast to mice of the control group.

Effect of selected nursing interventions in the reduction of after-pains and involution of uterus among post-natal mothers in selected hospitals

Background: The wonder of motherhood is the enjoyable journey that is felt only by the mother after giving birth. During postnatal period, the mother experiences problems like afterpain, back pain, pain in leg, breast engorgement, perineal discomfort, fatigue etc.&#x0D; Material and methods: This study focus on finding the effect of selected nursing interventions such as ambulation, emptying bladder, deep breathing exercise, fundal massage, alternate leg raising and Kegel’s exercise in reducing afterpain and improving involution of uterus among postnatal mother in selected hospitals of Bhubaneswar by quantitative experimental research approach of Quasi experimental non randomized control group design. Purposive sampling technique was used to select the 60 postnatal mothers. Data were collected through Self-structured Questionnaire on socio-demographic, standardized numeric pain intensity scale on after pain and Self-structured rating scale on assessing involution of uterus. Descriptive and inferential statistics were used for analyzed the collected data.&#x0D; Results: The study findings revealed that 83.3% of postnatal mothers had no pain and 96.7% had fundal height bellow umbilicus. After pain level in experimental group with the ‘t’ value was 20.79 at p value 0.05 level, which is statistically significant. There was significant difference observed between pre and post test mean score of after pain level and involution of uterus at p&lt;0.0001. There was notable association between parity of mother and afterpain level at χ2= 10.44.&#x0D; Conclusion: It conclude that rendering of planned nursing interventions to the postnatal mothers were helpful in dropping the level of after pains and improves in involution of uterus. Therefore, the investigator felt that more importance should be given to assess the post partum afterpain and involution of uterus experienced by the mother and measures should be taken seriously in order to reduce the afterpain and improves involution of uterus.

Ultrasonic control over the course of the postnatal period and diagnosis of obstetric pathology in the bitches

The article presents the results of ultrasound examination of uterine females in the postpartum period. It is established that during its physiological course on the 3rd day, the cervix and body of the uterus are placed in the pelvic cavity dorsally with respect to the bladder, and the horns of the uterus - in the abdominal cavity cranially, in the area of - the loops of the large intestine. On the ultrasound it is noted that the horns of the uterus are expanded, with a diameter of 15-18 mm. The walls of the horns are thickened, with sections from 4 mm to 6 mm. Its tissues are of average echogenicity, of heterogeneous consistency. Hypoechoic homogeneous content is observed in the visualized uterine cavity. In females with delayed litter during this period, uterine horns with a diameter of 1.91–1.96 cm were visualized, with a thickened wall that had hypoechoic areas. In addition, the endometrial relief was folded, uneven, and in some places, its desquamated fragments were visualized. Diagnostic sign of delay of litter was the detection in the uterine cavity of tissue structures of amniotic membranes with increased echogenicity. On the 7th day after childbirth, ultrasound signs of metritis were detected on the background of the delay of the litter. The uterine wall reached 3.3–3.9 cm, had a heterogeneous tissue structure and increased echogenicity. In the internal relief of the uterus, areas of desquamated endometrium were visualized and hyperechogenic contents were present in the uterine cavity. It is proved that ultrasound scan of the uterus into the bough is an eff ective method of monitoring the course of postpartum involution and provides early diagnosis of obstetric pathology. The main diagnostic ultrasound indicator for the delay of litter in the boughs is the visualization of the structures of the amniotic membranes in the uterine cavity, hyperechogenic areas and thickening of its walls. The development of postpartum metritis is indicated by signifi cant thickening of the uterus and its mucous membrane, areas of desquamated endometrium and the presence of hyperechoic content in the uterine cavity. Key words: bitch, postpartum period, uterine involution, delay of litter, metritis, ultrasound.

PD-1 Blockade During Post-partum Involution Reactivates the Anti-tumor Response and Reduces Lymphatic Vessel Density.

Post-partum breast cancer patients, or breast cancer patients diagnosed within 10 years of last childbirth, are ~3–5 times more likely to develop metastasis in comparison to non-post-partum, or nulliparous, patients. Additionally, post-partum patients have increased tumor-associated lymphatic vessels and LN involvement, including when controlled for size of the primary tumor. In pre-clinical, immune-competent, mouse mammary tumor models of post-partum breast cancer (PPBC), tumor growth and lymphogenous tumor cell spread occur more rapidly in post-partum hosts. Here we report on PD-L1 expression by lymphatic endothelial cells and CD11b+ cells in the microenvironment of post-partum tumors, which is accompanied by an increase in PD-1 expression by T cells. Additionally, we observed increases in PD-L1 and PD-1 in whole mammary tissues during post-partum mammary gland involution; a known driver of post-partum tumor growth, invasion, and metastasis in pre-clinical models. Importantly, implantation of murine mammary tumor cells during post-partum mammary gland involution elicits a CD8+ T cell population that expresses both the co-inhibitory receptors PD-1 and Lag-3. However, upon anti-PD-1 treatment, during post-partum mammary gland involution, the involution-initiated promotional effects on tumor growth are reversed and the PD-1, Lag-3 double positive population disappears. Consequently, we observed an expansion of poly-functional CD8+ T cells that produced both IFNγ and TNFα. Finally, lymphatic vessel frequency decreased significantly following anti-PD-1 suggesting that anti-PD-1/PD-L1 targeted therapies may have efficacy in reducing tumor growth and dissemination in post-partum breast cancer patients.

Improvement in post-partum uterine involution in rats treated with Apios americana.

Apios americana, a plant used as a staple ingredient of native American diets, has various properties, including anti-cancer, anti-hyperglycemic, hypotensive, and anti-inflammatory activity. In Japan, Apios is used as a post-natal medication. After parturition, women undergo a period of recovery as they return to pre-pregnancy conditions. However, few health products that aid post-partum recovery are on the market. We explored whether Apios can accelerate the post-partum recovery process, in particular the involution of the uterus. Female rats kept in individual cages were mated with two male rats, with the exception of the control group (female rats without mating, on basal diet; n=6). After delivery, rats were divided into five groups based on their diet: basal diet (model; n=6); basal diet+oral intake at 5.4 g/kg of Chanfukang granules (a Chinese patent medicine preparation for post-partum lochia) (positive; n=6); basal diet containing 10% Apios powder (low; n=6); basal diet containing 20% Apios powder (medium; n=6); basal diet containing 40% Apios powder (high; n=6). Five days later, uteri and spleens were weighed. Uterus and spleen indices for each rat were calculated by dividing visceral weight by the total weight. Hormone and cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Histological analysis of uteri was completed using hematoxylin and eosin (H&E) staining. Expression of matrix metalloproteinases and inhibitors in uteri was measured by western blotting. Our results showed that Apios treatment reduced the post-partum uterus index and regulated the hormone concentrations. Moreover, we found that the process of uterine involution was accelerated, based on morphological changes in the uterus. In addition, our results indicated that Apios alleviated the inflammatory response induced by the involution process. Transforming growth factor β was also found to be regulated by Apios. There were significant downregulation of matrix metalloproteinases and upregulation of their inhibitors by Apios, which suggested that Apios increased the rate of the collagen clearance process. These results, based on experimental observations at the molecular and protein levels, verified our hypothesis that Apios can improve uterine involution, and demonstrated the potential application of Apios in post-partum care.

Maternal and infant outcomes after elective neurosurgery for occupying lesions in saddle area during pregnancy

Objective To investigate the perinatal outcomes after elective neurosurgery in pregnant women complicated by space-occupying lesions in saddle area. Methods Clinical data were retrospectively collected and analyzed from five gravidas with space-occupying lesions in saddle area, who underwent neurosurgery at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to February 2018, including gestational age, perioperative management, surgical procedures, postoperative complications, pregnancy outcomes and pathological results. Results (1) Progressively deteriorated impaired vision was the chief complaint of all five patients. Space-occupying lesions in saddle area were detected by cranial MRI (plain scan). The surgical indication was clear as there was compression on optic nerve and a risk of blindness due to optic nerve atrophy. Two patients were operated in the third trimester and three in the second trimester. Postoperative pathology showed there were two cases with meningioma, two with pituitary macro adenoma and one with abscess of pituitary. Only one patient had mild postoperative cerebrospinal fluid rhinorrhea, which was improved three months later, and no complications were reported in the other four cases. All five patients had obvious improvement of vision after surgical intervention and no relapse was reported during a follow-up of 4-12 months. (2) Four gravidas continued their pregnancies to full or nearly full term, among which three underwent cesarean section due to obstetrical indications (one breech pregnancy, one twin pregnancy with scarred uterus and one complicated by hypertensive diseases of pregnancy with poor blood pressure control) and one delivered vaginally. Postpartum involution of the uterus was well in all of the four cases 42 d after delivery. The women with pituitary abscess terminated the pregnancy due to intraamniotic injection of ethacridine lactate at 20 weeks of gestation. Five neonates were all born with Apgar scores of 10 at 1, 5 and 10 min without any visible defects at birth and all grew and developed normally at 4-12 months after birth. Conclusions For gravidas with space-occupying lesions in saddle area, it is necessary to weigh the pros and cons and choose an individualized treatment plan. Resection of saddle area lesions in the second or third trimester backed by a multi-disciplinary team is a safe and feasible procedure if postponing the operation until delivery may cause irreversible or even life-threatening consequences. Key words: Pregnancy complications, neoplastic; Meningioma; Pituitary neoplasms; Neurosurgical procedures; Pregnancy outcome

Abstract ES2-2: Breast cancer's metastatic moment: How postpartum tissue involution facilitates progression

Abstract Virginia F. Borges* and Pepper J. Schedin*# Young Women's Breast Cancer Translational Program, University of Colorado, Anschutz Medical Campus, Aurora, Colorado*, and Knight Cancer Institute, Oregon Health &amp; Sciences University, Portland, Oregon#. Young women diagnosed with breast cancer (YWBC) have worse outcomes than older women, however the reasons remain poorly understood. The two dominant hypotheses, centered on tumor cell intrinsic and extrinsic biology respectively, appear in conflict. One hypothesis emphasizes the role of poor prognostic factors increased in young patients, such as ER-, PR- and Her2- disease. A second theory posits that host biology related to reproductive history drives poor outcomes, independent of tumor biologic subtype or size. However, studies addressing the roles of pregnancy in breast cancer risk and outcomes can appear discordant. Consequently, metrics of reproductive history are not always included in standard risk assessment tools, nor utilized to optimize treatment strategies. This education session is focused on bridging the gap between these two theories. Specifically, our data shows that tumor intrinsic risk factors for breast cancer progression are significantly modulated by reproductive biology and support the incorporation of reproductive history into clinical care decisions. There is a strong connection between reproductive history and risk of metastasis in breast cancer. Epidemiologic studies find a recent, but not concurrent, pregnancy to be an independent risk factor for breast cancer metastasis. Our own studies find a ∼3 fold increase in metastases in patients diagnosed postpartum (PPBC). Further, we and others find the postpartum risk-window persists for ≥10 years after child birth. Finally, interactions between breast cancer subtype and pregnancy history are observed, supporting roles for both tumor cell intrinsic and extrinsic biology in driving metastasis in young women. To investigate the mechanism of postpartum host biology on tumor progression, we developed rodent models of PPBC. We find the physiologic process of weaning-induced mammary gland involution to support immune suppression, tumor cell dissemination, and tumor cell access to vasculature — concerted processes that lead to breast cancer metastasis. In a prospective clinical trial, we developed a cohort of healthy, recently nursing women, and find similar tumor-promotional hallmarks in the human breast. Newly identified postpartum liver biology may also shed insight into metastasis in young women. We recently reported weaning-induced involution in the rodent liver. Further, the rodent involuting liver is highly permissive to breast cancer outgrowth. Potential relevance to women is suggested by a first-site-of-metastasis study in YWBC patients. Postpartum patients were at increased risk for liver metastasis, but not lung, brain or bone. Finally, our data showing normal mammary gland involution to be a COX-2 mediated process has led to preclinical modeling of NSAID based PPBC prevention and treatment strategies. Translating NSAID interventions to young women is potentially high-impact, as ∼50% of all YWBC patients are diagnosed within 10 years of their last pregnancy, putting them into an under-recognized, high risk, poor prognostic group. Citation Format: Schedin P. Breast cancer's metastatic moment: How postpartum tissue involution facilitates progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES2-2.