The Impact of Adenomyosis on Women's Fertility

Introduction This study evaluated the risk of preterm birth, low birthweight and small‐for‐gestational‐age neonates born to mothers with adenomyosis during pregnancy. Material and methods We used the results of a Japanese nationwide prospective birth cohort study, identifying 93 668 singleton deliveries from 2011 to 2014. We identified 314 pregnancies with adenomyosis using self‐reported questionnaires. Multiple logistic regression analyses were conducted to examine whether adenomyosis was associated with adverse pregnancy outcome. Maternal age, smoking status, method of conception, history of parity, fibroids, endometriosis and body mass index before pregnancy were analyzed as confounding factors. Results Multiple logistic regression analysis showed that pregnancy with adenomyosis was a risk factor for preterm birth at less than 37 weeks (adjusted odds ratio [aOR: 2.49, 95% confidence interval [CI] 1.89‐3.41), preterm birth at less than 34 weeks (aOR 1.91, 95% CI 1.02‐3.55), low birthweight <2500 g (aOR 1.83, 95% CI 1.36‐2.45), low birthweight <1500 g (aOR 2.39, 95% CI 1.20‐4.77) and small‐for‐gestational‐age neonates (aOR 1.68, 95% CI 1.13‐2.51). Conclusions This study found that pregnancy with adenomyosis was associated with preterm birth, low birthweight and small‐for‐gestational‐age neonates.

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“…miscarriage. 1,[6][7][8][9][10] However, obstetric and neonatal outcomes in patients with adenomyosis have not yet been thoroughly investigated.…”

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confidence: 99%

Risk of preterm birth, low birthweight and small‐for‐gestational‐age infants in pregnancies with adenomyosis: A cohort study of the Japan Environment and Children's Study

Yamaguchi

Kyozuka

Fujimori

et al. 2018

Acta Obstet Gynecol Scand

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“…This was accompanied by adenomyosis which is characterized by extension of the glands into the myometrium. Adenomyosis is known to reduce implantation 42 , which is associated with dysregulated adhesion molecules expression, including ITGB3 and SPP1 43 . Interestingly, we found elevated Spp1 expression in the Wnk1 d/d uteri during implantation, revealing another possible mechanism of impaired implantation in the Wnk1 d/d mice.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we found elevated Spp1 expression in the Wnk1 d/d uteri during implantation, revealing another possible mechanism of impaired implantation in the Wnk1 d/d mice. In addition to implantation, adenomyosis negatively impact pregnancy in several other ways including abnormal muscle contractility, inflammation and metabolism 42, 44, 45 . Interestingly, the ERM protein family member moesin (encoded by the MSN gene) has been correlated with adenomyosis in humans 21 , and we accordingly found higher Msn expression in the Wnk1 d/d mice.…”

Section: Discussionmentioning

confidence: 99%

WNK1 regulates uterine homeostasis and its ability to support pregnancy

Chi¹,

Wang²,

Huang

et al. 2020

Preprint

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21WNK1 is critical for uterine function as a mediator of stromal cell decidualization in vitro. 22 Here, we employed a mouse model with conditional WNK1 ablation from the female 23 reproductive tract to define its in vivo role in uterine biology. Loss of WNK1 altered uterine 24 morphology, causing endometrial epithelial hyperplasia, adenomyosis and a delay in 25 embryo implantation, ultimately resulting in compromised fertility. Mechanistic 26 investigations through transcriptomic and proteomic approaches uncovered the 27 regulatory role of WNK1 in controlling the PP2A-AKT-FOXO1 signaling axis. We show 28 that WNK1 interacts directly with PPP2R1A, which is crucial for PP2A phosphatase 29 activity. PP2A phosphatase in turn dephosphorylates AKT, thereby reducing its inhibitory 30 effect on FOXO1. This permits the nuclear entry of FOXO1 to transcriptionally regulate 31 implantation-associated genes. Our findings revealed a novel function of WNK1 in 32 regulating AKT-FOXO1 post-translational modification, and demonstrated that this 33 signaling pathway is critical in normal uterine physiology and pregnancy. 34 35 36 37 38 physiological functions, the underlying cellular components regulated by WNK1 may share 62 similarity between the different tissues. 63 64Despite its ubiquitous expression pattern, WNK1's role in organs other than those described 65 above remain unexplored. Given the role of WNK1 in regulating uterine stromal cell biology in 66 vitro, we hypothesized that WNK1 is essential in regulating uterine functions. To test this idea, we 67 established a conditional uterine WNK1 ablated mouse model, which resulted in severely 68 compromised fertility. We demonstrated that WNK1 is critical in maintaining uterine morphology, 69regulating epithelial proliferation and permitting appropriate embryo implantation. Additionally, we 70 defined the molecular mechanism through both transcriptomic and proteomic approaches to show 71 that the WNK1 signaling cascade begins by its direct interaction with the scaffold subunit of the 72 phosphatase complex PP2A, PPP2R1A. This interaction stabilized PP2A which prevented 73 unregulated AKT phosphorylation, ultimately alleviating AKT's inhibitory effect on FOXO1 nuclear 74 localization, an indispensable mediator of implantation 16 . 75 76 5 RESULTS 77 78 WNK1 is expressed in the uterus during early pregnancy in both humans and mice 79WNK1 expression was examined by immunohistochemistry in human endometrium during the 80 proliferative and mid-secretory phases as well as in the peri-implantation uterus of mice. In 81 humans, WNK1 is expressed in both the epithelial and stromal cells during the proliferative and 82 mid-secretory phases (Fig. 1.A). Similarly in mice, WNK1 is expressed during and after 83 implantation on gestation days (GDs) 4.5 and 5.5 (Fig. 1.B). These findings support the in vivo 84 involvement of WNK1 in regulating functions of the female reproductive tract. 85 86 WNK1 ablation altered uterine morphology and microenvironment 87To examine WNK1's function in the ...

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“…Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma in the myometrium and muscular hypertrophy/hyperplasia associated with increased vascularity and reactive fibrosis (1). According to the most convincing theory, adenomyosis was originally thought to originate from the invagination of the basalis of the endometrium into the inner myometrium (1,2). In addition, this disorder may possibly result from metaplastic alterations of Müllerian duct remnants.…”

Section: Introductionmentioning

confidence: 99%