[Individual hormonal profiles of blood progesterone and estradiol-17ß during the course of a reproductive cycle in mares]. / Individueller Konzentrationsverlauf von Progesteron und Östradiol-17ß im Blut bei Stuten während des Zyklus.

OBJECT AND AIM: This study presents the individual course of estradiol-17ß and progesterone concentrations in blood during the reproductive cycle in mares in order to point out physiological differences between individual animals and to aid in the interpretation of hormone values. MATERIAL AND METHODS: Concentrations of estradiol-17ß and progesterone were determined in seven mares over the course of their cycle. One mare was excluded from the study due to a physiologically deviating cycle. In addition, the mares' ovaries were examined via ultrasound on a daily basis in order to match the hormone values to morphological changes of the ovaries. RESULTS: In some cases, the mares showed considerable individual differences in their hormone concentrations, which also differed from the published comparative values in the literature. For example, two mares showed progesterone levels above basal levels at the time of ovulation. The postovulatory progesterone concentrations of the mares are characterized by marked fluctuations, which makes it difficult to provide reference values in the different sections of the corpus luteum phase. The length of the plateau phases averaged 12.3±1.5 days. The mare with double ovulation showed the highest progesterone concentrations. CONCLUSION: The measurement of plasma progesterone levels in mares should be interpreted only in the context of other test results. The very wide variation in estradiol-17ß concentrations makes it questionable whether the determination of this hormone value is of diagnostic value. CLINICAL RELEVANCE: When interpreting steroid hormone values in the ingravid cycle of a mare, the individual concentration courses must be taken into consideration, as they may deviate significantly from the published reference values.

A matter of new life and cell death: programmed cell death in the mammalian ovary.

BACKGROUND: The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are associated with drastic functional and morphological rearrangements of ovarian tissue, including follicular development and degeneration, and the formation and subsequent atrophy of the corpus luteum. The flawless execution of these reiterative processes is impossible without the involvement of programmed cell death (PCD). MAIN TEXT: PCD is crucial for efficient and careful clearance of excessive, depleted, or obsolete ovarian structures for ovarian cycling. Moreover, PCD facilitates selection of high-quality oocytes and formation of the ovarian reserve during embryonic and juvenile development. Disruption of PCD regulation can heavily impact the ovarian functions and is associated with various pathologies, from a moderate decrease in fertility to severe hormonal disturbance, complete loss of reproductive function, and tumorigenesis. This comprehensive review aims to provide updated information on the role of PCD in various processes occurring in normal and pathologic ovaries. Three major events of PCD in the ovary-progenitor germ cell depletion, follicular atresia, and corpus luteum degradation-are described, alongside the detailed information on molecular regulation of these processes, highlighting the contribution of apoptosis, autophagy, necroptosis, and ferroptosis. Ultimately, the current knowledge of PCD aberrations associated with pathologies, such as polycystic ovarian syndrome, premature ovarian insufficiency, and tumors of ovarian origin, is outlined. CONCLUSION: PCD is an essential element in ovarian development, functions and pathologies. A thorough understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of the ovary and the female reproductive system in general.

Cellular senescence in the pathogenesis of ovarian dysfunction.

The follicular microenvironment is crucial for normal ovarian function, and intra-ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens the adverse environment of various tissues and plays critical roles in chronological aging and various pathological conditions. Cellular senescence involves cell-cycle arrest, a senescence-associated secretory phenotype (SASP), macromolecular damage, and dysmetabolism. In this review, I summarize the latest knowledge regarding the role of cellular senescence in pathological conditions in the ovary, in the context of reproduction. Specifically, cellular senescence is known to impair follicular and oocyte health in cisplatin- and cyclophosphamide-induced primary ovarian insufficiency and to contribute to the pathogenesis of polycystic ovary syndrome (PCOS). In addition, cellular senescence is induced during the decline in ovarian reserve that is associated with chronological aging, endometriosis, psychological stress, and obesity, but it remains unclear whether it plays a causative role in these conditions. Finally, I discuss the potential for use of cellular senescence as a novel therapeutic target. The modification of SASP using a senomorphic and/or the elimination of senescent cells using a senolytic represent promising therapeutic strategies. Further elucidation of the role of cellular senescence in the effects of various insults on ovarian reserve, including chronological aging, as well as in pathogenesis of ovarian pathologies, including PCOS, may facilitate a new era of reproductive medicine.

Prolonged cold-preservation of domestic cat ovarian tissue is improved by extracellular solution but impaired by the fragmentation of ovary.

For domestic cats ovaries, recommended cold-storage limit is 24 h in Phosphate Buffered Saline (PBS) or Dulbecco`s PBS (DPBS). Here, we attempted to verify wheatear cat ovaries may benefit from more complex solutions during prolonged cold-storage (>24 h). First, the preservation capabilities of extracellular (SP+), intracellular (UW) solutions and DPBS supplemented with glutathione (DPBS+GSH) were compared using ovary fragments from the same ovary (n=10). Intact ovary stored in DPBS served as a control. Ovaries were kept at 4 °C for 48 h, and 72 h. In the second experiment, first ovary was stored in DPBS, second in SP+ or UW solution for 48 h (n = 12). Ovaries pairs stored in DPBS for 24 h served as a control (n=8). Tissue samples were evaluated directly after cold-storage and after following 24 h in vitro culture. Ovarian follicle morphology, apoptosis rates (cleaved caspase-3, TUNEL), and follicular growth activation (Ki-67) were assessed. Ovary fragmentation impaired follicular morphology preservation upon cold-storage comparing to intact ovary. However, ovarian fragments stored in UW for 48 h and in SP+ for 72 h presented better morphology than DPBS+GSH group. Comparison of intact ovaries cold-storage for 48 h showed that SP+ provided superior follicular morphology over DPBS, and it was comparable to the outcome of 24-hour storage. No follicular activation after in vitro culture was observed. Nevertheless, tissue culture increased considerably caspase-3 cleavage and TUNEL detection. The ovary fragmentation prior to cold-storage is not recommended in domestic cats. Replacement of DPBS with SP+ solution for whole ovary and UW solution for ovarian tissue fragments improves follicular structure preservation during 48-hour cold-storage.

Positive effects of rutin on female reproduction.

This article reviews the source and properties of rutin (vitamin P), its general physiological and medicinal effects and their mechanisms, but the main subject of it is the currently available knowledge concerning the character and mechanisms of action of rutin on female reproductive processes. The available data demonstrate the stimulatory action of rutin on female reproductive processes: it can promote ovarian follicles development and ovulation, ovarian cyclicity, and viability of ovarian cells. On the other hand, it can suppress ovarian cancer cell and tumour development by inhibition of cell proliferation and growth and activation of their apoptosis and death. Furthermore, it could be able to prevent other reproductive disorders (ischaemia, polycystic ovarian syndrome, toxic effects of chemotherapy, nanoparticles and toluene). Rutin could exert its effects via changes in the release and reception of gonadotropin, ovarian steroid hormones, prostaglandins, cytokines, VEGF, as well as in intracellular regulators and markers of oxidative and inflammatory processes, proliferation, apoptosis and angiogenesis.

In Vitro Maturation, In Vitro Oogenesis, and Ovarian Longevity.

This paper will review a remarkable new approach to in vitro maturation "IVM" of oocytes from ovarian tissue, based on our results with in vitro oogenesis from somatic cells. As an aside benefit we also have derived a better understanding of ovarian longevity from ovary transplant. We have found that primordial follicle recruitment is triggered by tissue pressure gradients. Increased pressure holds the follicle in meiotic arrest and prevents recruitment. Therefore recruitment occurs first in the least dense inner tissue of the cortico-medullary junction. Many oocytes can be obtained from human ovarian tissue and mature to metaphase 2 in vitro with no need for ovarian stimulation. Ovarian stimulation may only be necessary for removing the oocyte from the ovary, but this can also be accomplished by simple dissection at the time of ovary tissue cryopreservation. By using surgical dissection of the removed ovary, rather than a needle stick, we can obtain many oocytes from very small follicles not visible with ultrasound. A clearer understanding of ovarian function has come from in vitro oogenesis experiments, and that explains why IVM has now become so simple and robust. Tissue pressure (and just a few "core genes" in the mouse) direct primordial follicle recruitment and development to mature oocyte, and therefore also control ovarian longevity. There are three distinct phases to oocyte development both in vitro and in vivo: in vitro differentiation "IVD" which is not gonadotropin sensitive (the longest phase), in vitro gonadotropin sensitivity "IVG" which is the phase of gonadotropin stimulation to prepare for meiotic competence, and IVM to metaphase II. On any given day 35% of GVs in ovarian tissue have already undergone "IVD" and "IVG" in vivo, and therefore are ready for IVM.

Increased Hepatocyte Growth Factor Secretion by Placenta-Derived Mesenchymal Stem Cells Improves Ovarian Function in an Ovariectomized Rat Model via Vascular Remodeling by Wnt Signaling Activation.

The vascular network contributes to the development of follicles. However, the therapeutic mechanism between vascular remodeling and ovarian functions is still unclear. Therefore, we demonstrated whether increased HGF by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in an ovariectomized rat model via vascular remodeling by Wnt signaling activation. We established a half-ovariectomized rat model in which damaged ovaries were induced by ovariectomy of half of each ovary, and PD-MSCs (5 × 105 cells) were transplanted by intravenous injection. Three weeks after transplantation, rats in all groups were sacrificed. We examined the secretion of HGF by PD-MSCs through culture medium. The vascular structure in injured ovarian tissues was restored to a greater extent in the PD-MSC transplantation (Tx) group than in the nontransplantation (NTx) group (* p < 0.05). The expression of genes related to Wnt signaling (e.g., LRP6, GSK3ß, ß-catenin) was significantly increased in the Tx group compared to the NTx group (* p < 0.05). However, the expression of genes related to vascular permeability (e.g., Asef, ERG3) was significantly decreased in the Tx group compared to the NTx group (* p < 0.05). Follicular development was improved in the Tx group compared to the NTx group (* p < 0.05). Furthermore, to evaluate vascular function, we cocultivated PD-MSCs after human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and we analyzed the vascular formation assay and dextran assay in HUVECs. Cocultivation of PD-MSCs with injured HUVECs enhanced vascular formation and decreased endothelial cell permeability (* p < 0.05). Also, cocultivation of PD-MSCs with explanted ovarian tissues improved follicular maturation compared to cocultivation of the Wnt inhibitor-treated PD-MSCs with explanted ovarian tissues. Therefore, HGF secreted by PD-MSCs improved ovarian function in rats with ovarian dysfunction by decreasing vascular permeability via Wnt signaling.

Chemotherapy-induced ovarian damage and protective strategies.

More than 9.2 million women worldwide suffer from cancer, and about 5% of them are at reproductive age. Chemotherapy-induced impairment of fertility affects the quality of life of these women. Several chemotherapeutic agents have been proven to cause apoptosis and autophagy by inducing DNA damage and cellular stress. Injuries to the ovarian stroma and micro-vessel network are also considered as pivotal factors resulting in ovarian dysfunction induced by chemotherapeutic agents. Primordial follicle pool over-activation may also be the mechanism inducing damage to the ovarian reserve. Although many studies have explored the mechanisms involved in chemotherapy-induced reproductive toxicity, the exact molecular mechanisms have not been elucidated. It is essential to understand the mechanisms involved in ovarian damage, in order to develop potential protective treatments to preserve fertility. In this article, we reviewed the current knowledge on the mechanism of chemotherapy-induced ovarian damage and possible protective strategies that prevent the ovary from such damages.

New insight into the role of macrophages in ovarian function and ovarian aging.

Macrophages (MΦs) are the most abundant leukocytes in mammalian ovaries that have heterogeneity and plasticity. A body of evidence has indicated that these cells are important in maintaining ovarian homeostasis and they play critical roles in ovarian physiological events, such as folliculogenesis, ovulation, corpus luteum formation and regression. As females age, ovarian tissue microenvironment is typified by chronic inflammation with exacerbated ovarian fibrosis. In response to specific danger signals within aged ovaries, macrophages polarize into different M1 or M2 phenotypes, and specialize in unique functions to participate in the ovarian aging process. In this review, we will focus on the physiologic roles of MΦs in normal ovarian functions. Furthermore, we will discuss the roles of MΦs in the process of ovarian senescence, as well as the novel techniques applied in this field.

The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response.

BACKGROUND: Assisted reproduction faces a significant obstacle in the form of poor ovarian response (POR) to controlled ovarian stimulation. To address this challenge, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. Our previous research has demonstrated that menstrual blood-derived-mesenchymal stromal cells (MenSCs) injected into the ovaries of women with POR can increase pregnancy rates. The objective of this study was to examine whether MenSC therapy could enhance ovarian reserve parameters and pregnancy outcomes in a larger population of individuals with POR. METHOD: This study consisted of 180 infertile individuals with POR who declined oocyte donation. Participants were divided into two groups: those who received bilateral MenSCs intraovarian injection and those who received no intervention. Our primary aim was to compare the rates of spontaneous pregnancy between the two groups, followed by an investigation of any alterations in the ovarian reserve parameters, such as serum FSH, AMH, and AFC levels, as well as the ICSI/IVF outcomes, in both groups of participants. RESULTS: The MenSC therapy exhibited a favourable tolerability profile and did not raise any safety concerns. Following the 2-month follow-up period, women who received MenSC treatment demonstrated a significantly higher rate of spontaneous pregnancy (P < 0.005) and an improvement in anti-Müllerian hormone (AMH) levels (P = 0.0007) and antral follicle count (AFC) (P < 0.001), whereas the control group demonstrated a considerable decline in these parameters (Both P < 0.001). The MenSC therapy led to a greater number of mature oocytes and embryos among women who underwent ICSI/IVF. Our age subgroup analysis demonstrated a significant difference in the number of spontaneous pregnancies and ICSI/IVF outcomes between the treatment and control groups only among individuals below 40 years of age. CONCLUSION: The results of our study indicate that MenSCs treatment may be a viable option for treating women experiencing POR. However, in order to be widely implemented in clinical practice, the clinical effectiveness of MenSCs therapy will need to be established through rigorous prospective randomized clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308 . IRCT, IRCT20180619040147N4. Registered 08/01/2020.

CHEK2 signaling is the key regulator of oocyte survival after chemotherapy.

Cancer treatments can damage the ovarian follicle reserve, leading to primary ovarian insufficiency and infertility among survivors. Checkpoint kinase 2 (CHEK2) deficiency prevents elimination of oocytes in primordial follicles in female mice exposed to radiation and preserves their ovarian function and fertility. Here, we demonstrate that CHEK2 also coordinates the elimination of oocytes after exposure to standard-of-care chemotherapy drugs. CHEK2 activates two downstream targets-TAp63 and p53-which direct oocyte elimination. CHEK2 knockout or pharmacological inhibition preserved ovarian follicle reserve after radiation and chemotherapy. However, the lack of specificity for CHEK2 among available inhibitors limits their potential for clinical development. These findings demonstrate that CHEK2 is a master regulator of the ovarian cellular response to damage caused by radiation and chemotherapy and warrant the development of selective inhibitors specific to CHEK2 as a potential avenue for ovario-protective treatments.

Advances in the mechanisms related to follicle loss after frozen-thawed ovarian tissue transplantation.

Ovaries are important reproductive and endocrine organs in women. Ovarian tissue cryopreservation and transplantation technology can not only solve the fertility problems of patients, but also may improve female endocrine problems. This is particularly important for patients in urgent need of radiotherapy and chemotherapy, and for women with prepubertal malignant tumors. However, follicle loss after freeze-thawing is a key challenge for effective ovarian tissue transplantation and leads to poor transplant outcomes. Therefore, it is crucial to elucidate the mechanisms underlying follicle loss after transplantation. This paper reviews current research on the mechanisms of follicle loss after frozen-thawed ovarian tissue transplantation, including the activation, apoptosis, and pyroptosis mechanisms of primordialfollicles. Further, it highlights the requirement of more experimental studies for improving ovarian tissue transplantation methods.

Involvement of cathepsin L in the degradation and degeneration of postovulatory follicle of the medaka ovary†.

Cathepsin L plays physiological and pathological roles in immune responses, cancer, metamorphosis, and oogenesis in several species. However, the function of Cathepsin L in medaka ovaries remains unclear. Therefore, here, we examined the physiological functions of Cathepsin L in the medaka ovaries. Cathepsin L mRNA transcripts and proteins were found to be constitutively expressed in the ovaries of Oryzias latipes over a 24-h spawning cycle. Expression was localized within the oocyte cytoplasm of growing follicles and the follicle layer of preovulatory and postovulatory follicles. Moreover, the active form of Cathepsin L was highly expressed in the follicle layer of periovulatory follicles and the ovaries 2-6 h after ovulation. Recombinant Cathepsin L was activated under acidic conditions and exhibited enzymatic activity in acidic and neutral pH conditions. However, extracellular matrix proteins were degraded by recombinant Cathepsin L under acidic, not neutral pH conditions. Cathepsin L was secreted from preovulatory follicles, while active recombinant Cathepsin L was detected in the conditioned medium of a medaka cell line, OLHNI-2. Mechanistically, recombinant Cathepsin L activates recombinant urokinase-type plasminogen activator-1, which is expressed within the follicle layers post-ovulation. Meanwhile, the treatment of medakas with an E-64 or anti-Cathepsin L antibody effectively blocked follicular layer degeneration and degradation after ovulation, whereas in vitro ovulation was not inhibited by either. Collectively, the findings of this study indicate that although Cathepsin L does not impact ovulation in medakas, it contributes to the degeneration and degradation of the follicle layers following ovulation via activation of urokinase-type plasminogen activator-1, and not via the degradation of extracellular matrix proteins.

Kisspeptin decreases the adverse effects of human ovarian vitrification by regulating ROS-related apoptotic occurrences.

Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this study, the effects of kisspeptin on the improvement of the vitrification and thawing results of human ovarian tissues were investigated. In this work, 12 ovaries from patients who underwent hysterectomy were collected laparoscopically, and then 32 samples from each of their tissues were taken. Haematoxylin and eosin (H&E) staining was performed to check the normality of the ovarian tissue and, subsequently, the samples were allocated randomly into four groups, including: (1) fresh (control), (2) vitrification, (3) vitrified + 1 µM kisspeptin, and (4) vitrified + 10 µM kisspeptin groups. After vitrification, thawing, and tissue culture processes, H&E staining for tissue quality assessment, terminal deoxynucleotidyl transferase dUTP nick end labelling assay for apoptosis evaluation, and malondialdehyde (MDA), superoxide dismutase (SOD), and ferric reducing ability of plasma tests for oxidative stress appraisal were carried out. Our histological results showed incoherency of ovarian tissue morphology in the vitrification group compared with other groups. Other findings implicated increased apoptosis rate and MDA concentration and reduced SOD activity and total antioxidant capacity (TAC) in the vitrification group compared with the control group (P < 0.05). Moreover, decreased apoptosis rate and MDA concentration, and increased TAC and SOD function were observed in the vitrification with kisspeptin groups (1 µM and 10 µM) compared with the vitrified group (P < 0.05). Our reports express that kisspeptin is an effective agent to overcome the negative effects of vitrification by regulating reactive oxygen species-related apoptotic processes.

Can flaxseed, chia or puncture vine affect mare ovarian cell functions and prevent the toxic effect of the environmental contaminant toluene?

The aim of this in vitro study was to examine the potential effect of functional food plant extracts, namely, extracts of flaxseed (Linum usitatissimum L.), chia (Salvia hispanica) and puncture vine (Tribulus terrestris L.), on basic mare ovarian cell functions and their response to the environmental contaminant toluene. Mare granulosa cells were incubated with and without toluene (0, 0.02, 0.2 or 2.0 µg/mL) in the presence or absence of flaxseed, chia and puncture vine extracts (10 µg/mL). Markers of cell proliferation (accumulation of proliferating cell nuclear antigen, PCNA) and apoptosis (accumulation of bax), viability (Trypan blue extrusion) and the release of progesterone (P), oxytocin (OT) and prostaglandin F 2 alpha (PGF) were measured. Toluene reduced all other measured parameters except OT release. All the tested plants were able to reduce cell viability and the release of P and PGF, but they did not influence other indexes. Moreover, flaxseed mitigated toluene action on ovarian cell proliferation, apoptosis, OT and PGF, whilst puncture vine prevented and inverted toluene action on P and PGF ourput. Chia extract did not modify toluene action on any parameter. On the other hand, toluene was able to promote the inhibitory action of flaxseed on cell viability and P release and to prevent the inhibitory action of all the plant extracts on PGF release. The present study (1) is the first demonstration, that flaxseed, chia and puncture vine can directly suppress mare ovarian cell functions, (2) shows that toluene can suppress basic ovarian cell functions and modify the reproductive effect of food plants and (3) demonstrates the ability of flaxseed and puncture vine, but not of chia, to prevent some toxic effect of toluene on mare ovarian cell functions.

Low estradiol production of non-laying whooping cranes (Grus americana) is associated with the failure of small follicles to enter follicular hierarchy.

For endangered species managed ex situ, production of offspring is a key factor to ensure healthy and self-sustaining populations. However, current breeding goals for the whooping crane (Grus americana) are impeded by poor reproduction. Our study sought to better understand mechanisms regulating ovarian function in ex situ managed whooping cranes and the regulatory function of the hypothalamic-pituitary-gonadal (HPG) axis in relation to follicle formation and egg laying. To characterize hormonal regulation of follicular development and ovulation, we collected weekly blood samples from six female whooping cranes during two breeding seasons, for a total of 11 reproductive cycles. The plasma samples were assessed for follicle stimulating hormone, luteinizing hormone, estradiol, and progesterone and the yolk precursors vitellogenin and very low-density lipoprotein. Ultrasonographic examination of the ovary was conducted at the time of blood collection. Preovulatory follicles (>12 mm) were present in laying cycles (n = 6) but absent in non-laying cycles (n = 5). The patterns of plasma hormone and yolk precursor concentrations corresponded to the stage of follicle development. Specifically, gonadotropin and yolk precursor concentrations increased as follicles transitioned from the non-yolky to yolky stage but did not increase further as the follicle advanced to preovulatory and ovulatory stages. Estrogen and progesterone concentrations increased as follicle size increased and reached peak concentrations (P < 0.05) when follicles developed to ovulatory and preovulatory stages, respectively. While overall mean circulating gonadotropin, progesterone, and yolk precursor concentrations did not differ for laying versus non-laying cycles, mean plasma estradiol in laying cycles was significantly higher than that in non-laying cycles. In summary, the findings suggested that disruption of mechanisms regulating follicle recruitment is likely responsible for the oviposition failure of the captive female whooping crane.

Estradiol-independent restoration of T-cell function in post-reproductive females.

Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune systems show only moderate changes in T-cell subsets tend to live longer than age-matched siblings that display extensive T-cell subset aging. Importantly, at the time of reproductive decline, the increase in disease risks in women significantly outpace those of men. In female mice, there is a significant decline in central and peripheral naïve T-cell subsets at the time of reproductive failure. Available evidence indicates that this naïve T-cell decline is sensitive to ovarian function and can be reversed in post-reproductive females by transplantation of young ovaries. The restoration of naïve T-cell subsets due to ovarian transplantation was impressive compared with post-reproductive control mice, but represented only a partial recovery of what was lost from 6 months of age. Apparently, the influence of ovarian function on immune function may be an indirect effect, likely moderated by other physiological functions. Estradiol is significantly reduced in post-reproductive females, but was not increased in post-reproductive females that received new ovaries, suggesting an estradiol-independent, but ovarian-dependent influence on immune function. Further evidence for an estradiol-independent influence includes the restoration of immune function through the transplantation of young ovaries depleted of follicles and through the injection of isolated ovarian somatic cells into the senescent ovaries of old mice. While the restoration of naïve T-cell populations represents only a small part of the immune system, the ability to reverse this important functional parameter independent of estradiol may hold promise for the improvement of post-reproductive female immune health. Further studies of the non-reproductive influence of the ovary will be needed to elucidate the mechanisms of the relationship between the ovary and health.

Analysis of Physiological Control of Adult Drosophila Oogenesis by Interorgan Communication.

Tissue homeostasis is dependent on the interaction between various organs within an organism in response to physiological inputs. The adult Drosophila melanogaster ovary is sensitive to environmental challenges and has recently been shown to be regulated by signaling from peripheral organs. To dissect the intricate coordination between overall organism health and reproduction, it is necessary to meticulously characterize both experimental tools and oogenesis processes. This chapter provides a guide for the careful analysis of interorgan communication in regulating oogenesis in adult Drosophila melanogaster.