Clinicopathological features and prognostic value of CD276 expression in female reproductive system malignancies: A meta-analysis.

The relationship between CD276 and malignancies of the female reproductive system has previously been controversial. The purpose of this study was to evaluate the predictive value of CD276 expression in clinicopathological features and prognosis of female reproductive system malignant tumors through meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang databases were searched for studies published up to December 2022 on the role of CD276 expression in the clinicopathological features and prognosis of female reproductive system malignancies. STATA 14.0 was used for meta-analysis. A total of 10 studies were included, involving 840 patients with malignant tumors of the female reproductive system. The results showed that in terms of clinicopathological features: CD276 expression was closely related to lymph node status [OR = 2.33， 95 %CI = 1.32-4.11， P = 0.003], tumor differentiation [OR = 2.15， 95 %CI = 1.27-3.63, P = 0.004], and FIGO stage [OR = 2.58， 95 %CI = 1.44-4.61, P = 0.001] of reproductive system malignant tumors. In terms of prognosis: CD276 expression is strongly associated with shorter OS in patients with female reproductive system malignancies [HR = 3.33, 95 % CI = 1.36-8.15, P = 0.01]. CD276 may be a new target for immunotherapy and a biomarker for predicting poor prognosis of female reproductive system malignancies.

Predictive and prognostic biomarkers in female genital tract tumours: an update highlighting their clinical relevance and practical issues.

The evaluation of biomarkers by molecular techniques and immunohistochemistry has become increasingly relevant to the treatment of female genital tract tumours as a consequence of the greater availability of therapeutic options and updated disease classifications. For ovarian cancer, mutation testing for BRCA1/2 is the standard predictive biomarker for poly(ADP-ribose) polymerase inhibitor therapy, while homologous recombination deficiency testing may allow the identification of eligible patients among cases without demonstrable BRCA1/2 mutations. Clinical recommendations are available which specify how these predictive biomarkers should be applied. Mismatch repair (MMR) protein and folate receptor alpha immunohistochemistry may also be used to guide treatment in ovarian cancer. In endometrial cancer, MMR immunohistochemistry is the preferred test for predicting benefit from immune checkpoint inhibitor (ICI) therapy, but molecular testing for microsatellite instability may have a supplementary role. HER2 testing by immunohistochemistry and in situ hybridisation is applicable to endometrial serous carcinomas to assess trastuzumab eligibility. Immunohistochemistry for oestrogen receptor and progesterone receptor expression may be used for prognostication in endometrial cancer, but its predictive value for hormonal therapy is not yet proven. POLE mutation testing and p53 immunohistochemistry (as a surrogate for TP53 mutation status) serve as prognostic markers for favourable and adverse outcomes, respectively, in endometrial cancer, especially when combined with MMR testing for molecular subtype designation. For cervical cancer, programmed death ligand 1 immunohistochemistry may be used to predict benefit from ICI therapy although its predictive value is under debate. In vulvar cancer, p16 and p53 immunohistochemistry has established prognostic value, stratifying patients into three groups based on the human papillomavirus and TP53 mutation status of the tumour. Awareness of the variety and pitfalls of expression patterns for p16 and p53 in vulvar carcinomas is crucial for accurate designation. It is hoped that collaborative efforts in standardising and optimising biomarker testing for gynaecological tumours will contribute to evidence-based therapeutic decisions.

The effect of the female genital tract and gut microbiome on reproductive dysfunction.

Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The interaction between the microbiome and reproductive health has become an increasingly compelling area of study. Disruption of the female genital tract microbiome can significantly impact the metabolism of amino acids, carbohydrates, and lipids, increasing susceptibility to reproductive tract diseases such as vaginitis, chronic endometritis, endometrial polyps, endometriosis, and polycystic ovary syndrome. The gut microbiome, considered an endocrine organ, plays a crucial role in the reproductive endocrine system by interacting with hormones like estrogen and androgens. Imbalances in the gut microbiome composition can lead to various diseases and conditions, including polycystic ovary syndrome, endometriosis, and cancer, although research on their mechanisms remains limited. This review highlights the latest advancements in understanding the female genital tract and gut microbiomes in gynecological diseases. It also explores the potential of microbial communities in the treatment of reproductive diseases. Future research should focus on identifying the molecular mechanisms underlying the association between the microbiome and reproductive diseases to develop new and effective strategies for disease prevention, diagnosis, and treatment related to female reproductive organs.

EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.

Desmoplastic small round cell tumor (DSRCT) is a high-grade, primitive round cell sarcoma classically associated with prominent desmoplastic stroma, coexpression of keratin and desmin, and a characteristic EWSR1::WT1 gene fusion. DSRCT typically arises in the abdominopelvic cavity of young males with diffuse peritoneal spread and poor overall survival. Although originally considered to be pathognomonic for DSRCT, EWSR1::WT1 gene fusions have recently been detected in rare tumors lacking the characteristic morphologic and immunohistochemical features of DSRCT. Here, we report 3 additional cases of neoplasms other than conventional DSCRCT with EWSR1::WT1 gene fusions that occurred outside the female genital tract. Two occurred in the abdominopelvic cavities of a 27-year-old man and a 12-year-old girl, whereas the third arose in the axillary soft tissue of an 85-year-old man. All cases lacked prominent desmoplastic stroma and were instead solid and cystic with peripheral fibrous pseudocapsules and occasional intervening fibrous septa. Necrosis was either absent (1/3) or rare (2/3), and mitotic activity was low (<1 to 3 per 10 hpf). In immunohistochemical studies, there was expression of smooth muscle actin (3/3) and desmin (3/3), rare to focal reactivity for EMA (2/3), and variable expression of CK AE1/AE3 (1/3). Myogenin and MyoD1 were negative, and C-terminus-specific WT1 was positive in both cases tested (2/2). All 3 tumors followed a more indolent clinical course with 2 cases demonstrating no evidence of disease at 20 and 44 months after resection. The patient from case 3 died of other causes at 14 months with no evidence of recurrence. DNA methylation profiling showed that the 3 cases clustered with DSRCT; however, they demonstrated fewer copy number variations with 2 cases having a flat profile (0% copy number variation). Differential methylation analysis with hierarchical clustering further showed variation between the 3 cases and conventional DSRCT. Although further study is needed, our results, in addition to previous reports, suggest that EWSR1::WT1 gene fusions occur in rare and seemingly distinctive tumors other than conventional DSRCT with indolent behavior. Proper classification of these unusual soft tissue tumors with EWSR1::WT1 gene fusions requires direct correlation with tumor morphology and clinical behavior, which is essential to avoid overtreatment with aggressive chemotherapy.

Expression of IRS2 in the female reproductive system during the estrous cycle in mice.

Insulin receptor substrate 2 (IRS2) participates in reproduction; however, the location and expression of IRS2 in the reproductive system of female mice is not clear. We used real-time quantitative polymerase chain reaction (RT-PCR), western blot and immunohistochemical staining to investigate the expression of IRS2 in the ovary, oviduct and uterus of female mice during the estrous cycle. We found that IRS2 was expressed in all reproductive organs of mouse and that the expression level changed with the estrous phases. The expression of IRS2 in reproductive organs was greatest during estrus.

An Overview of the Current Known and Unknown Roles of Vitamin D3 in the Female Reproductive System: Lessons from Farm Animals, Birds, and Fish.

Recent studies have clearly shown that vitamin D3 is a crucial regulator of the female reproductive process in humans and animals. Knowledge of the expression of vitamin D3 receptors and related molecules in the female reproductive organs such as ovaries, uterus, oviduct, or placenta under physiological and pathological conditions highlights its contribution to the proper function of the reproductive system in females. Furthermore, vitamin D3 deficiency leads to serious reproductive disturbances and pathologies including ovarian cysts. Although the influence of vitamin D3 on the reproductive processes of humans and rodents has been extensively described, the association between vitamin D3 and female reproductive function in farm animals, birds, and fish has rarely been summarized. In this review, we provide an overview of the role of vitamin D3 in the reproductive system of those animals, with special attention paid to the expression of vitamin D3 receptors and its metabolic molecules. This updated information could be essential for better understanding animal physiology and overcoming the incidence of infertility, which is crucial for optimizing reproductive outcomes in female livestock.

Molecular mechanism of progesterone action in the female reproductive system / Molekularny mechanizm dzialania progesteronu w zenskim ukladzie rozrodczym.

Progesterone (P4) is a steroid hormone which participate in many processes in the female reproductive system. The hormone is produced mainly by the corpus luteum (CL), however, also the ovarian follicles, uterine tissues and placenta are able to produce P4. Progesterone is involved in the regulation of the sexual cycle, as well as in the initiation and maintenance of pregnancy. The hormone may affect cell function by genomic mechanism, through nuclear P4 receptors (PGR), and via nongenomic mechanism, through the membrane P4 receptors, such as progesterone receptor membrane component (PGRMC) 1 and 2, and membrane progestin receptors (mPR) α, ß and γ. The genomic mechanism of P4 action leads to the expression of target genes and the synthesis of new proteins, while the nongenomic mechanism modifies various intracellular signaling pathways. The integration of these two mechanisms of P4 activity leads to the suitable regulation of the cell, tissue and, consequently, the response of organism to the hormone.

Female Reproductive Systems: Hormone Dependence and Receptor Expression.

The female reproductive system which consists of the ovaries, uterus (myometrium, endometrium), Fallopian tubes, cervix and vagina is exquisitely sensitive to the actions of steroid hormones. The ovaries play a key role in the synthesis of bioactive steroids (oestrogens, androgens, progestins) that act both within the tissue (intracrine/paracrine) as well as on other reproductive organs following release into the blood stream (endocrine action). Sex steroid receptors encoded by the oestrogen (ESR1, ESR2), progesterone (PR) and androgen (AR) receptor genes, which are members of the superfamily of ligand activated transcription factors are widely expressed within these tissues. These receptors play critical role(s) in regulation of cell proliferation, ovulation, endometrial receptivity, myometrial cell function and inflammatory cell infiltration. Our understanding of their importance has been informed by studies on human tissues and cells, which have employed immunohistochemistry as well as a wide range of molecular and genetic methods to identify which processes are dependent steroid ligand activation. The development of mice with targeted deletions of each of these receptors has provided complementary data that has extended our appreciation of cell-cell interactions in the fine tuning of reproductive tissue function. This large body of work has formed the basis of new and improved therapeutics to treat conditions such as infertility.

Immunohistochemical Expression of LHRH Receptor in Different Compartments of Female Genital Tract in Patients With Endometrial Cancer.

Luteinizing hormone-releasing hormone receptor (LHRHR) expression has been reported in various cancers, including endometrial neoplasms. Thus, LHRHR provides a potential point for therapeutic approach using LHRH analogs as carrier molecules for chemotherapeutic agents in this cancer population. However, clinical data did not prove any potential benefits for patients. We decided to assess LHRHR expression in patients with endometrial cancer to explain possible lack of efficacy in previous clinical reports. LHRHR expression was assessed immunohistochemically in different anatomic and histogenetic compartments of female genital tract of patients with endometrial cancer. The study sample consisted of paraffin tissue blocks obtained from patients who has undergone primary surgery owing to endometrial cancer. Strong LHRHR expression was found in endometrial cancer, fallopian tube, and concurrent atypical hyperplasia. Interestingly, LHRHR expression showed significant differences depending on the respective compartment of the ovary analyzed. Level of LHRHR expression in patients with primary advanced and unresectable disease, particularly in certain ovarian compartments may be substantially lower, which may influence the use of new targeted therapy regimens. The studies on secondary Müllerian system compartment and its hormonal receptor status may be crucial to understand mechanisms of lack of efficacy of LHRH hybrid molecules anti-cancer treatment.

Progress of Adipokines in the Female Reproductive System: A Focus on Polycystic Ovary Syndrome.

Adipose tissue, one type of loose connective tissue in the human body, maintains the primary task of energy storage. Adipose tissue is not only an energy reservoir but also plays a vital role as the largest endocrine organ of the whole body via releasing a variety of adipokines, which participate in many pathophysiological processes, such as energy metabolism regulation, glucose and lipid metabolism, and inflammation. Polycystic ovary syndrome (PCOS) is a disorder that mainly involves the female reproductive system, affecting women of childbearing age particularly. Insulin resistance (IR) and hyperandrogenemia (HA) have been implicated as a critical link involving the etiology and outcome of PCOS. A great deal of studies has bridged the gap between adipokines (such as Adiponectin, Chemerin, Metrnl, Apelin, Resistin, Visfatin, Leptin, Vaspin, Lipocalin 2, and Omentin) and reproductive fitness. In this review, we will focus on the adipokines' functions on PCOS and come up with some points of view on the basis of current research.

Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways.

Advanced glycation end products (AGEs), a heterogenous group of products formed by the reaction between protein and reducing sugars, can form endogenously due to non-enzymatic reactions or by exogenous sources such as diet where considerable increase in AGEs is observed due to the modification of food mainly by thermal processing. Recent studies have suggested that AGEs could impact, via inducing inflammation and oxidative stress, the reproductive health and fertility in both males and females. This review presents a summary of recently published data pertaining to the pathogenesis of dietary AGEs and their receptors as well as their potential impact on female reproductive health. More specifically, it will present data pertaining to dietary AGEs' involvement in the mechanistic pathogenesis of polycystic ovary syndrome, ovarian dysfunction, as well as the AGEs' effect perinatally on the female offspring reproduction. Understanding the mechanistic impact of dietary AGEs on female reproduction can help contribute to the development of targeted pharmacological therapies that will help curb rising female infertility.

Exosomes - Spectacular role in reproduction.

Exosomes are nano-sized structures that are found in semen, epididymal -fluid, endometrium, as well as in follicular fluid. They are responsible for transporting bioactive cargo- proteins, lipids, and nucleic acids. Exosomes have been proven to influence processes in both female and male reproductive systems, including gametogenesis, acrosomal reaction, sperm capacitation, and embryo implantation in the endometrium. Exosomes are made of the same particles as the cells they come from and are secreted by normal and pathological cells. Therefore, exosomes can reflect the physiological state of cells. Moreover, due to the transportation of biomolecules, they participate in intercellular communication and can be used as biomarkers of many diseases, including ovarian, endometrial and prostate cancer. Identification of exosomes as biomarkers could contribute to a better understanding of genital dysfunction and fertility disorders.

Physiological and pathological roles of Ang II and Ang- (1-7) in the female reproductive system.

The local Renin-Angiotensin System (RAS) has been demonstrated to exist in a wide range of tissues and organs, In the female reproductive system, it is mainly found in the ovary, uterus and placenta. The RAS system is made up of a series of active substances and enzymes, in addition to the circulating endocrine renin-angiotensin system. The active peptides Angiotensin II (Ang II) and Angiotensin (1-7) (Ang-(1-7)), in particular, appear to have distinct activities in the local RAS system, which also controls blood pressure and electrolytes. Therefore, in addition to these features, angiotensin and its receptors in the reproductive system seemingly get involved in reproductive processes, such as follicle growth and development, as well as physiological functions of the placenta and uterus. In addition, changes in local RAS components may induce reproductive diseases as well as pathological states such as cancer. In most tissues, Ang II and Ang- (1-7) seem to maintain antagonistic effects, but this conclusion is not always true in the reproductive system, where they play similar functions in some physiological and pathological roles. This review investigated how Ang II, Ang- (1-7) and their receptors were expressed, localized, and active in the female reproductive system. This review also summarized their effects on follicle development, uterine and placental physiological functions. The changes of local RAS components in a series of reproductive system diseases including infertility related diseases and cancer and their influence on the occurrence and development of diseases were elucidated. This article reviews the physiological and pathological roles of Ang II and Ang- (1-7) in female reproductive system,a very intricate system of tissue factors that operate as agonists and antagonists was found. Besides, the development of novel therapeutic strategies targeting components of this system may be a research direction in future.

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review.

The progesterone hormone regulates the human menstrual cycle, pregnancy, and parturition by its action via the different progesterone receptors and signaling pathways in the female reproductive tract. Progesterone actions can be exerted through classical and non-classical receptors, or even a combination of both. The former are nuclear receptors whose activation leads to transcriptional activity regulation and thus in turn leads to slower but long-lasting responses. The latter are composed of progesterone receptors membrane components (PGRMC) and membrane progestin receptors (mPRs). These receptors rapidly activate the appropriate intracellular signal transduction pathways, and they can subsequently initiate specific cell responses or even modulate genomic cell responses. This review covers our current knowledge on the mechanisms of action and the relevance of classical and non-classical progesterone receptors in female reproductive tissues ranging from the ovary and uterus to the cervix, and it exposes their crucial role in female infertility.

The damage effect of heat stress and psychological stress combined exposure on uterus in female rats.

AIMS: Explore the effects of heat stress and psychological stress combined exposure on the uterus and its underlying mechanisms. MAIN METHODS: Sixty female Sprague-Dawley rats were randomly assigned to four groups: control group, psychological stress group, high ambient temperature group, and high ambient temperature combined with psychological stress group. All treatments were administered for two weeks. During this period, the estrous cycle, body weights and rectal temperature were measured regularly. Then, ovarian weight coefficient, serum estradiol (E2) and progesterone (P) concentration, uterine histomorphological alterations, levels of tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD), and the expressions of ovarian hormone receptors, leukemia inhibitory factor (LIF) and its receptor, homeobox gene A10 (HoxA10), Wnt5a, Wnt7a, ß-catenin, and P-ß-cateninY142 in the uterus and endometrium were detected. KEY FINDINGS: High temperature combined with psychological stress lead to body weight, body temperature, ovarian hormones and estrus cycle disorder, uterine gland ducts expansion and endometrial thickness reduction, and the decreased expression of endometrial receptivity markers (LIF and HoxA10). Further, disturbed expression of E2 and P receptors in endometrium, elevated MDA and TNF-α levels, and decreased Wnt5a, Wnt7a and P-ß-cateninY142 content were found. Our data suggested that co-exposure to high temperature and psychological stress could aggravate uterine damage probably by inducing ovarian hormonal disorder and the subsequent oxidative stress and inflammation, and reduce the endometrial function through suppressing Wnt signaling. SIGNIFICANCE: This will provide the scientific basis for improving female reproductive health, and preventing and treating reproductive disorders.

Drug delivery strategies for management of women's health issues in the upper genital tract.

The female upper genital tract (UGT) hosts important reproductive organs including the cervix, uterus, fallopian tubes, and ovaries. Several pathologies affect these organ systems such as infections, reproductive issues, structural abnormalities, cancer, and inflammatory diseases that could have significant impact on women's overall health. Effective disease management is constrained by the multifaceted nature of the UGT, complex anatomy and a dynamic physiological environment. Development of drug delivery strategies that can overcome mucosal and safety barriers are needed for effective disease management. This review introduces the anatomy, physiology, and mucosal properties of the UGT and describes drug delivery barriers, advances in drug delivery technologies, and opportunities available for new technologies that target the UGT.

Obesity induces morphological and functional changes in female reproductive system through increases in NF-κB and MAPK signaling in mice.

BACKGROUND: Recently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility. METHODS: To deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues. RESULTS: The obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status. CONCLUSIONS: These HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-ß estradiol.

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-ß estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

The role of androgens in women's health and wellbeing.

Androgens in women, as well as in men, are intrinsic to maintenance of (i) reproductive competency, (ii) cardiac health, (iii) appropriate bone remodeling and mass retention, (iii) muscle tone and mass, and (iv) brain function, in part, through their mitigation of neurodegenerative disease effects. In recognition of the pluripotency of endogenous androgens, exogenous androgens, and selected congeners, have been prescribed off-label for several decades to treat low libido and sexual dysfunction in menopausal women, as well as, to improve physical performance. However, long-term safety and efficacy of androgen administration has yet to be fully elucidated. Side effects often observed include (i) hirsutism, (ii) acne, (iii) deepening of the voice, and (iv) weight gain but are associated most frequently with supra-physiological doses. By contrast, short-term clinical trials suggest that the use of low-dose testosterone therapy in women appears to be effective, safe and economical. There are, however, few clinical studies, which have focused on effects of androgen therapy on pre- and post-menopausal women; moreover, androgen mechanisms of action have not yet been thoroughly explained in these subjects. This review considers clinical effects of androgens on women's health in order to prevent chronic diseases and reduce cancer risk in gynecological tissues.

PAQR7: An intermediary mediating nongenomic progesterone action in female reproductive tissue.

Progestin and adipoQ receptor 7 (PAQR7) as an indispensable member of membrane progestin receptors in the Progestin and adipoQ receptor (PAQR) family that mediates nongenomic progesterone actions, initiated rapidly at the cell surface. Previous research demonstrated the distribution of PAQR7, which was mainly expressed in reproductive tissues, including ovary and testis. In the male reproductive system, PAQR7 is involved in progestin-induced sperm hypermotility. However, reports studying PAQR7 in female reproductive tissue mainly concentrate on oocyte maturation in fish, its expression in the ovary and gestational tissue, and regulation of uterine functions in mammals. Despite recent advances, many aspects of progestin signaling through PAQR7 are still unclear, especially in female reproductive tissue. Therefore, we reveal the structure and characteristics of PAQR7 and conclude the putative progestin-induced action mediated by PAQR7 in female reproductive tissue, such as the development of ovarian follicles, apoptosis of granulosa cells, oocyte maturation, and development of certain diseases, among others, to review the function of PAQR7 in the female reproductive system in detail.