Authors: Ivana Winkler, Alexander Tolkachov, Fritjof Lammers...

The female reproductive tract (FRT) undergoes extensive remodeling during reproductive cycling. This recurrent remodeling and how it shapes organ-specific aging remains poorly explored. Using single-cell and spatial transcriptomics, we systematically characterized morphological and gene expression changes occurring in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrous cycle, during decidualization, and into aging. These analyses reveal that fibroblasts play central-and highly organ-specific-roles in FRT remodeling by orchestrating extracellular matrix (ECM) reorganization and inflammation. Our results suggest a model wherein recurrent FRT remodeling over reproductive lifespan drives the gradual, age-related development of fibrosis and chronic inflammation. This hypothesis was directly tested using chemical ablation of cycling, which reduced fibrotic accumulation during aging. Our atlas provides extensive detail into how estrus, pregnancy, and aging shape the organs of the female reproductive tract and reveals the unexpected cost of the recurrent remodeling required for reproduction.

Topics: Animals; Female; Mice; Pregnancy; Aging; Genitalia, Female; Inflammation; Uterus; Vagina; Single-Cell Analysis

PubMed: 38325365
DOI: 10.1016/j.cell.2024.01.021

Authors: Saskia van der Straaten, Alexander Springer, Aleksandra Zecic...

CONTEXT

Standardized description of external genitalia is needed in the assessment of children with atypical genitalia.

OBJECTIVES

To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs).

DESIGN, SETTING

A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018.

PATIENTS AND METHODS

EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0-12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0-24 months) and 181 preterm babies, and 111 babies with atypical genitalia.

RESULTS

The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6-11.5); in males 28-32 weeks 11.5 (9.2-12); in males 33-36 weeks 11.5 (10.5-12) and in full-term males 12 (10.5-12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia.

CONCLUSIONS

EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research.

Topics: Cross-Sectional Studies; Disorders of Sex Development; Europe; Female; Genitalia, Female; Genitalia, Male; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Reference Values; Reproducibility of Results

PubMed: 31665438
DOI: 10.1210/clinem/dgz142

Authors: Salvatore Giovanni Vitale, Federico Ferrari, Michał Ciebiera...

The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the -dominated flora seems to play a pivotal role in determining fertility, and in particular showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as , , species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

Topics: Cervix Uteri; Endometrium; Female; Genitalia, Female; Humans; Infertility, Female; Lactobacillus; Microbiota; Vagina

PubMed: 35008605
DOI: 10.3390/ijms23010180

Authors: Rachel M Keeffe, Patricia L R Brennan

What is the vagina? This seemingly simple question has a rather complex answer, depending on whether we use a functional or a developmental definition. The terminal portion of the female reproductive tract that opens to the environment initially served as a conduit for eggs to be laid, and in species with external fertilization the distal oviduct may be specialized for oviposition but there is no vagina. In animals with internal fertilization, this terminal section of the oviduct interacts with the sperm and the intromittent organ leading to functional specialization of this region that we often call a vagina in insects and some vertebrates. Here we address the evolution, morphology and diverse functions of the vagina and some of the unknown questions that remain to be addressed in the study of this remarkable structure.

Topics: Animals; Humans; Female; Male; Semen; Genitalia, Female; Spermatozoa; Oviducts; Oviposition; Fertilization

PubMed: 37339591
DOI: 10.1016/j.cub.2023.05.012

Authors: Patricia L R Brennan

While most birds do not have external genitalia, in a small number of species the males have penises, which can be either intromittent or non-intromittent. Brennan provides an overview of bird genitalia, including speculation about the evolutionary forces involved.

Topics: Male; Animals; Genitalia; Biological Evolution; Penis; Birds

PubMed: 36283360
DOI: 10.1016/j.cub.2022.09.015

Review

Authors: Emma S Gargus, Hunter B Rogers, Kelly E McKinnon...

Engineered male and female biomimetic reproductive tissues are being developed as autonomous in vitro units or as integrated multi-organ in vitro systems to support germ cell and embryo function, and to display characteristic endocrine phenotypic patterns, such as the 28-day human ovulatory cycle. In this Review, we summarize how engineered reproductive tissues facilitate research in reproductive biology, and overview strategies for making engineered reproductive tissues that might eventually allow the restoration of reproductive capacity in patients.

Topics: Biocompatible Materials; Bioprinting; Cell Encapsulation; Female; Genitalia, Female; Genitalia, Male; Germ Cells; Humans; Hydrogels; Male; Microfluidics; Printing, Three-Dimensional; Reproduction; Testis; Tissue Engineering; Tissue Scaffolds; Tissue Transplantation

PubMed: 32251392
DOI: 10.1038/s41551-020-0525-x

Authors: W W Schultz, P van Andel, I Sabelis...

OBJECTIVE

To find out whether taking images of the male and female genitals during coitus is feasible and to find out whether former and current ideas about the anatomy during sexual intercourse and during female sexual arousal are based on assumptions or on facts.

DESIGN

Observational study.

SETTING

University hospital in the Netherlands.

METHODS

Magnetic resonance imaging was used to study the female sexual response and the male and female genitals during coitus. Thirteen experiments were performed with eight couples and three single women.

RESULTS

The images obtained showed that during intercourse in the "missionary position" the penis has the shape of a boomerang and 1/3 of its length consists of the root of the penis. During female sexual arousal without intercourse the uterus was raised and the anterior vaginal wall lengthened. The size of the uterus did not increase during sexual arousal.

CONCLUSION

Taking magnetic resonance images of the male and female genitals during coitus is feasible and contributes to understanding of anatomy.

Topics: Adult; Arousal; Coitus; Feasibility Studies; Female; Genitalia, Female; Genitalia, Male; Humans; Magnetic Resonance Imaging; Male; Penis; Uterus

PubMed: 10600954
DOI: 10.1136/bmj.319.7225.1596

Authors: Nadia S Sloan, Leigh W Simmons

In this Quick guide, Nadia Sloan and Leigh Simmons introduce the diverse and fascinating biology of female genitalia.

Topics: Animals; Biodiversity; Biological Evolution; Female; Genitalia, Female; Humans; Species Specificity

PubMed: 33352121
DOI: 10.1016/j.cub.2020.10.074

Authors: Gerald R Cunha, Laurence S Baskin

Topics: Animals; Clitoris; Embryonic Development; Female; Genitalia; Humans; Hypospadias; Male; Mice; Morphogenesis; Penis; Receptors, Androgen; Signal Transduction; Urethra

PubMed: 31881402
DOI: 10.1016/j.diff.2019.10.008

Review

Authors: Kazuhide Takada, Vyacheslav G Melnikov, Ryoki Kobayashi...

The female reproductive tract (FRT) and remote/versatile organs in the body share bidirectional communication. In this review, we discuss the framework of the "FRT-organ axes." Each axis, namely, the vagina-gut axis, uterus-gut axis, ovary-gut axis, vagina-bladder axis, vagina-oral axis, uterus-oral axis, vagina-brain axis, uterus-brain axis, and vagina-joint axis, is comprehensively discussed separately. Each axis could be involved in the pathogenesis of not only gynecological diseases but also diseases occurring apart from the FRT. Although the microbiota is clearly a key player in the FRT-organ axes, more quantitative insight into the homeostasis of the microbiota could be provided by host function measurements rather than current microbe-centric approaches. Therefore, investigation of the FRT-organ axes would provide us with a multicentric approach, including immune, neural, endocrine, and metabolic aspects, for understanding the homeostatic mechanism of women's bodies. The framework of the FRT-organ axes could also provide insights into finding new therapeutic approaches to maintain women's health.

Topics: Female; Humans; Genitalia, Female; Uterus; Vagina; Ovary; Microbiota

PubMed: 36798125
DOI: 10.3389/fimmu.2023.1110001