Shan Wang

Infertility affects about 17.5% of couples, with male factors accounting for approximately 50% of cases. Cytoskeletal remodeling is increasingly recognized as a critical component of male reproductive function, particularly in the regulation of testosterone synthesis by Leydig cells. However, the underlying molecular mechanisms remain poorly defined. Rho-associated coiled-coil-containing kinase (ROCK), a key cytoskeletal regulator, influences actin dynamics, impacting intracellular trafficking. In this study, we investigated the roles of ROCK1 and ROCK2 in Leydig cells using the TM3 cell model. Pharmacological inhibition of ROCK activity with Y-27632 impaired actin cytoskeleton organization, reduced the phosphorylation of LIMK, COFILIN, and MLC2, and disrupted the colocalization of F-actin with StAR and cholesterol, thereby decreasing testosterone production. Furthermore, RNA-seq revealed that hCG promotes transcription of steroidogenesis-related genes, while ROCK inhibition reverses this effect. Silencing of ROCK1 via siRNA mimicked the effects of ROCK-i, suppressing steroidogenic gene expression and testosterone synthesis. In contrast, ROCK2 knockdown enhanced testosterone secretion, promoted F-actin remodeling, and increased traffic of cholesterol targeting mitochondria. These opposing effects triggered distinct responses in the SCAP–SREBP2 axis, indicating a feedback mechanism regulating cholesterol homeostasis. Collectively, our findings uncover the isoform-specific roles of ROCK1 and ROCK2 in coordinating cytoskeletal dynamics and steroidogenic activity, providing new insights into the regulation of male reproductive endocrinology and identifying potential therapeutic targets for androgen deficiency and male infertility.

Background: To assess the variations in protein C (PC) activity throughout pregnancy and investigate potential correlations between plasma PC activities and adverse pregnancy outcomes. Methods: A retrospective cohort study was conducted among 1511 women who underwent PC activity testing at a hospital in China from June 2011 to August 2021. t-test, Kruskal Wallis, Fisher’s exact test, logistic regression and receiver operator characteristic (ROC) analysis were used for analysis of data. Results: The PC activity demonstrated a significant increase during the second trimester of pregnancy. The PC activity was found to be lower in pregnant women with a history of thrombosis (median, 95.70% [interquartile range (IQR), 85.50–114.60%]) as compared to those without (median, 109.00% [IQR, 95.00–124.60%], p = 0.008) or with current thrombosis (median, 101.10% [IQR, 85.30–117.00%]) compared to those without such events (median, 109.00% [IQR, 95.00–124.78%], p = 0.013). History of thrombosis was the independent risk factor of current thrombosis during pregnancy (odd ratio (OR) 260.57; 95% confidence interval (95% CI), 76.751–884.689; p < 0.001). The PC activity of 125 cases of threatened abortion was significantly lower than that of asymptomatic women (median, 100.80% [IQR, 91.30–113.15%] vs median, 110.00% [IQR, 95.65–125.00%], p < 0.001). Multivariate analysis showed that the low PC activity (OR 0.985; 95% CI, 0.976–0.994, p = 0.001), gestational age (OR 0.960; 95% CI, 0.946–0.975; p < 0.001) and hypothyroidism (OR 1.888; 95% CI, 1.054–3.381; p < 0.05) were risk factors for threatened abortion. There was no difference in PC activity between fetal loss, hypertensive disorder complicating pregnancy (HDCP), fetal growth restriction (FGR), oligohydramnios, placental abruption and those without. Conclusions: Women with a history of thrombosis and decreased PC activity are risk factors for thrombosis and threatened abortion during pregnancy, respectively. However, no significant correlation was observed between PC activity and fetal loss, HDCP, FGR, oligohydramnios or placental abruption.

To investigate the effects of the human chromosomal segregation 1-like (CSE1L) gene on the biological behaviour of human placental cells.The CSE1L gene plays important roles in chromosome segregati...

Objectives: The development of maternal-fetal immune tolerance and adequate trophoblast function are essential for the establishment and maintenance of pregnancy. Human leukocyte antigen (HLA), the major histocompatibility complex (MHC) antigen specific to humans, plays an important role in placentation and is involved in many pregnancy-associated diseases. HLA-C is the only classical MHC I gene expressed at the maternal-fetal interface. To investigate whether HLA-C plays an independent role in regulating the development of trophoblasts, we explored the effect of HLA-C expression on placental development. Methods: The role of HLA-C in the growth and migration of trophoblast JAR and HTR-8/Svneo cell lines was investigated after HLA-C-expressing lentivirus transfection. Results: The MTT assay and colony formation assay showed that HLA-C promoted cell proliferation. Furthermore, cell cycle analysis showed that HLA-C overexpression accelerated the transition of trophoblast cells from the G0/G1 phase to the S phase. However, FACS analysis and migration assay indicated that HLA-C had no significant influence on trophoblast apoptosis and migration. Conclusion: Our study demonstrated for the first time that besides being involved in immune tolerance, HLA-C can directly promote placental growth without interacting with immune cells, which could provide a new insight into studying the functions of HLA-C at the maternal-fetal interface.

Objectives: To analyse the effect of dydrogesterone use during pregnancy on uterine fibroids, pregnancy complications, and pregnancy outcome. Material and methods: In all, 372 pregnant women with uterine fibroids who were treated at the Affiliated Provincial Hospital of Shandong University were included in this study. Thirty-three of these women received dydrogesterone and constituted the treatment group, and the 27 women who were found to have uterine fibroids during the first trimester but did not receive intervention to prevent miscarriage composed the control group. The changes in uterine fibroids before and after pregnancy and the pregnancy complications were recorded; immunohistochemistry was used to detect the expression of progesterone receptor (PR) and proliferation- and apoptosis-related proteins in the uterine fibroid tissue. Results: No significant difference was observed in the change in uterine fibroid volume during pregnancy between the treatment group and the control group (p > 0.05). The percentage of uterine fibroids with red degeneration was lower in the treatment group than in the control group, but the difference was not statistically significant. No significant difference was observed in newborn weight, height, Apgar score, threatened miscarriage, or premature birth, among other characteristics, between the two groups (p > 0.05). Immunohistochemistry showed no significant difference in the expression of PR, cyclinD1, insulin-like growth factor (IGF1), or B-cell lymphoma 2 (Bcl2) between the two groups. Conclusions: The use of dydrogesterone during pregnancy has no significant effect on uterine fibroids, pregnancy progression, or pregnancy outcomes in pregnant patients with uterine fibroids. Objectives: To analyse the effect of dydrogesterone use during pregnancy on uterine fibroids, pregnancy complications, and pregnancy outcome. Material and methods: In all, 372 pregnant women with uterine fibroids who were treated at the Affiliated Provincial Hospital of Shandong University were included in this study. Thirty-three of these women received dydrogesterone and constituted the treatment group, and the 27 women who were found to have uterine fibroids during the first trimester but did not receive intervention to prevent miscarriage composed the control group. The changes in uterine fibroids before and after pregnancy and the pregnancy complications were recorded; immunohistochemistry was used to detect the expression of progesterone receptor (PR) and proliferation- and apoptosis-related proteins in the uterine fibroid tissue. Results: No significant difference was observed in the change in uterine fibroid volume during pregnancy between the treatment group and the control group (p > 0.05). The percentage of uterine fibroids with red degeneration was lower in the treatment group than in the control group, but the difference was not statistically significant. No significant difference was observed in newborn weight, height, Apgar score, threatened miscarriage, or premature birth, among other characteristics, between the two groups (p > 0.05). Immunohistochemistry showed no significant difference in the expression of PR, cyclinD1, insulin-like growth factor (IGF1), or B-cell lymphoma 2 (Bcl2) between the two groups. Conclusions: The use of dydrogesterone during pregnancy has no significant effect on uterine fibroids, pregnancy progression, or pregnancy outcomes in pregnant patients with uterine fibroids.