Reproductive disorders

  • Article
    | Open Access

    The sperm head-to-tail coupling apparatus ensures sperm head-tail integrity, but mechanistic insights remain limited. Here the authors demonstrate that CENTLEIN links and controls the interaction between SUN5 and PMFBP1, indicating that its impairments might be associated with acephalic spermatozoa syndrome.

    • Ying Zhang
    • , Chao Liu
    •  & Li Yuan
  • Article
    | Open Access

    Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

    • Yalda Afshar
    • , Jiantong Dong
    •  & Yazhen Zhu
  • Article
    | Open Access

    Open fires can increase heavy exposure to hazardous particulate matters, and thus harm human health, particularly among the vulnerable individuals, such as pregnant women. Here, the authors show an association between maternal exposure to fire smoke and increased risk of pregnancy loss in South Asia.

    • Tao Xue
    • , Guannan Geng
    •  & Tong Zhu
  • Article
    | Open Access

    Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs.

    • Sungsam Gong
    • , Francesca Gaccioli
    •  & D. Stephen Charnock-Jones
  • Article
    | Open Access

    Anterior vaginal prolapse (AVP), the most common form of pelvic organ prolapse, has deleterious effects on women’s health. Here the authors employ single-cell RNA-seq to construct a transcriptomic atlas of vaginal wall cells from AVP patients, and find that extracellular matrix dysregulation and immune reaction are associated with AVP.

    • Yaqian Li
    • , Qing-Yang Zhang
    •  & Lan Zhu
  • Article
    | Open Access

    Miscarriage affects around 15% of clinically confirmed pregnancies. Here the authors carry out a large genome-wide association study for sporadic and multiple consecutive miscarriage and suggest links with placental biology.

    • Triin Laisk
    • , Ana Luiza G. Soares
    •  & Cecilia M. Lindgren
  • Article
    | Open Access

    Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

    • Valgerdur Steinthorsdottir
    • , Ralph McGinnis
    •  & Linda Morgan
  • Article
    | Open Access

    Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. Here the authors identify an optimum dietary macronutrient balance that can rectify PCOS reproductive traits in a mouse model of PCOS, while metabolic features were less sensitive to diet changes.

    • Valentina Rodriguez Paris
    • , Samantha M. Solon-Biet
    •  & Kirsty A. Walters
  • Article
    | Open Access

    How maternal RNA clearance is regulated in human preimplantation embryos is unclear. Here, the authors show there is a potential correlation between maternal mRNA decay defects and early developmental arrest from in vitro fertilized human embryos, suggesting that M-decay and Z-decay pathways may regulate such early development.

    • Qian-Qian Sha
    • , Wei Zheng
    •  & Heng-Yu Fan
  • Article
    | Open Access

    Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications with limited treatment options. Here the authors show that dysregulation of bile acids increases risk for PTB in pregnant women while restoring bile acid homeostasis delays or prevents PTB in the mouse models.

    • Sangmin You
    • , Ai-Min Cui
    •  & Ruitang Deng
  • Article
    | Open Access

    Somatic mutations in MED12 have been implicated as the causal genetic lesion in the majority of uterine leiomyomas. Here, the authors profile the chromatin landscape of matched normal and leiomyoma tissues and find that changes in enhancer acetylation, enhancer-promoter interaction strength, differential enhancer usage and transcription factor AP-1 occupancy are significant drivers of transcriptional dysregulation in MED12 mutant leiomyomas.

    • Mthabisi B. Moyo
    • , J. Brandon Parker
    •  & Debabrata Chakravarti
  • Article
    | Open Access

    Glycoprotein ZP1 is a component of the oocyte’s zona pellucida (ZP), and mutations in human ZP1 are linked to female infertility. Here, using structure-function analysis, the authors suggest that filament cross-linking by ZP1 is required to form a stable ZP in human, and infertility mutations interfere with cross-linking.

    • Kaoru Nishimura
    • , Elisa Dioguardi
    •  & Luca Jovine
  • Article
    | Open Access

    The transcription factor SOX17 is important for uterine gland formation, fertility, and embryo implantation in mouse. Here the authors show that SOX17 is upstream of Indian hedgehog to regulate mouse uterine receptivity, and their analysis of uterine tissue from endometriosis patients suggests the same function in humans.

    • Xiaoqiu Wang
    • , Xilong Li
    •  & Francesco J. DeMayo
  • Article
    | Open Access

    The onset of mammalian puberty is sensitive to metabolic changes and nutritional status, but the mechanisms underlying this phenomenon are poorly understood. Here the authors show that the epigenetic regulator of transcription, SIRT1, mediates the effects of under and overnutrition on pubertal timing by controlling the expression of Kiss1 in hypothalamic neurons.

    • M. J. Vazquez
    • , C. A. Toro
    •  & M. Tena-Sempere
  • Article
    | Open Access

    Asthenozoospermia is a major cause of male infertility, and multiple morphological abnormalities of the flagella (MMAF) is a particularly severe form. Here, using whole-exome sequencing of 78 MMAF patients, the authors identify mutations in two WDR proteins, CFAP43 and CFAP44, and confirm that these proteins are required for flagellogenesis in mouse and Trypanosoma brucei.

    • Charles Coutton
    • , Alexandra S. Vargas
    •  & Pierre F. Ray
  • Article
    | Open Access

    Embryo implantation initiates the interaction of the blastocyst with the uterus and occurs within a specialised crypt formed by uterine epithelial cells. Here, using 3D imaging techniques of wild type and mutant uteri, the authors show that crypt formation occurs with preexisting glands of the uterus, opening communication between glands and the implanting embryo.

    • Jia Yuan
    • , Wenbo Deng
    •  & Sudhansu. K. Dey
  • Article
    | Open Access

    About a quarter of pre-menopausal women will suffer from heavy menstrual bleeding in their lives. Here, Maybin and colleagues show hypoxia and subsequent activation of HIF-1α during menses are required for normal endometrial repair, and identify pharmacological stabilisation of HIF-1α as a potential therapeutic strategy for this debilitating condition.

    • Jacqueline A. Maybin
    • , Alison A. Murray
    •  & Hilary O. D. Critchley
  • Article
    | Open Access

    Endometriosis is a common gynaecological disease but the underlying pathogenesis is poorly understood, however there is a strong familial component. Here the authors conduct a genome wide association study and identify a novel susceptibility locus that correlates with disease severity.

    • Valgerdur Steinthorsdottir
    • , Gudmar Thorleifsson
    •  & Kari Stefansson
  • Article
    | Open Access

    Hypoxia has diverse effects on aquatic life. Wang et al.show that reproductive defects resulting from hypoxia are epigenetically heritable in Japanese rice fish, and that this intergenerational inheritance is accompanied by differential methylation and gene expression in sperm.

    • Simon Yuan Wang
    • , Karen Lau
    •  & Rudolf Shiu-Sun Wu
  • Article |

    Non-obstructive azoospermia (NOA) is a major cause of male infertility. Here, the authors provide insight into the genetic basis of NOA by identifying three new genetic risk loci in a genome-wide association study and reporting a fourth potential NOA susceptibility locus based on a Drosophilaknockdown experiment.

    • Zhibin Hu
    • , Zheng Li
    •  & Jiahao Sha
  • Article |

    The kisspeptin receptor GPR54 is implicated in the maintenance of mammalian fertility. Kirilov et al.study GPR54 mutant mice and identify a subset of neurons in the brain expressing gonadotropin-releasing hormone as the critical site for kisspeptin action.

    • Milen Kirilov
    • , Jenny Clarkson
    •  & Allan E. Herbison