Aim: To evaluate obstetric outcomes in embryo transfer (ET) during estrogen with progestin hormone replacement therapy (HRT) cycles using assisted reproductive technology (ART). Methods: Of the 118 singleton pregnancies conceived with ART and delivered between January 2015 and December 2017, we reviewed the data of 87 cases that had information on HRT at the time of ET. Data on pregnancy outcomes included the presence of small for gestational age fetuses, hypertensive disorders of pregnancy, placenta previa (including low-lying placenta), placental abruption and placenta accreta spectrum (including placenta accreta, placenta increta and placenta percreta). We investigated the relationship between HRT cycles and adverse placental outcomes (placenta accreta spectrum, placental abruption, placenta previa, hypertensive disorders of pregnancy and small for gestational age fetuses). We then analyzed the associations that correlated with adverse placental outcomes. Results: Patients with ET during HRT cycles were more likely to have placenta accreta spectrum. During the study period, 87 out of 118 singleton live births using ART had information on HRT (60 HRT cycles and 27 ovulation cycles). The incidence of placenta accreta spectrum was significantly higher in the HRT cycle group than in the ovulation cycle group (HRT cycle, 31.7% [19 of 60] vs ovulation cycle, 7.4% [2 of 27]; P < 0.01). Conclusion: The obstetric outcomes occurring in pregnancies involving HRT use may differ among ET cycles. ET during HRT cycles were associated with adverse obstetric outcomes due to placenta accreta spectrum. The potential interaction between HRT cycles and adverse placental events is novel and warrants further investigation.
Background Since the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1‐derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression. Methods Since AR expression was negative in W12 cells and HaCaT cells, a human male skin‐derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions. Results DHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR‐transfected W12 cells. Si‐RNA treatments showed that DHT induced the expression of squamous differentiation‐related genes in AR‐transfected W12 cells via an ELF3‐dependent pathway. DHT also reduced FOXP4 expression in AR‐transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN. Conclusion Androgen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone‐induced differentiation therapy against CIN1 and CIN2.
Problem: In the cell column of anchoring villi, the cytotrophoblast differentiates into extravillous trophoblast (EVT) and invades the endometrium in contact with maternal immune cells. Recently, chemokines were proposed to regulate the decidual immune response. To investigate the roles of chemokines around the anchoring villi, we examined the expression profiles of chemokines in the first-trimester trophoblast-derived Swan71 cells using a three-dimensional culture model. Method of Study:The gene expressions in the spheroid-formed Swan71 cells were examined by microarray and qPCR analyses. The protein expressions were examined by immunochemical staining. The chemoattractant effects of spheroid-formed Swan71 cells were examined by migration assay using monocyte-derived THP-1 cells. Results:The expressions of an EVT marker, laeverin, and matrix metalloproteases, MMP2 and MMP9, were increased in the spheroid-cultured Swan71 cells. Microarray and qPCR analysis revealed that mRNA expressions of various chemokines, CCL2, CCL7, CCL20, CXCL1, CXCL2, CXCL5, CXCL6, CXCL8, and CXCL10, in the spheroid-cultured Swan71 cells were up-regulated as compared with those in the monolayer-cultured Swan71 cells. These expressions were significantly suppressed by hypoxia. Migration assay showed that culture media derived from the spheroid-formed Swan71 cells promoted THP-1 cell migration. Conclusion:This study indicated that chemokine expressions in Swan71 cells increase under a spheroid-forming culture and the culture media have chemoattractant effects.Since three-dimensional cell assembling in the spheroid resembles the structure of the cell column, this study also suggests that chemokines play important roles in the interaction between EVT and immune cells in their early differentiation stage.
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