Circulating immunity protects the female reproductive tract from Chlamydia infection.

Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Chlamydia Despite robust establishment of localized memory lymphocytes within the FRT, naïve mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting Chlamydia infection via the vaginal route. Blocking the rapid mobilization of circulating memory CD4 T cells to the FRT inhibited this protective response. These data demonstrate that secondary protection in the FRT can occur in the complete absence of tissue-resident immune cells. The ability to confer robust protection to barrier tissues via circulating immune memory provides an unexpected opportunity for vaccine development against infections of the FRT.

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.

Melatonin and its mechanism of action in the female reproductive system and related malignancies.

Melatonin (N-acetyl-5-methoxytryptamine), the main product of pineal gland in vertebrates, is well known for its multifunctional role which has great influences on the reproductive system. Recent studies documented that melatonin is a powerful free radical scavenger that affects the reproductive system function and female infertility by MT1 and MT2 receptors. Furthermore, cancer researches indicate the influence of melatonin on the modulation of tumor cell signaling pathways resulting in growth inhibitor of the both in vivo/in vitro models. Cancer adjuvant therapy can also benefit from melatonin through therapeutic impact and decreasing the side effects of radiation and chemotherapy. This article reviews the scientific evidence about the influence of melatonin and its mechanism of action on the fertility potential, physiological alteration, and anticancer efficacy, during experimental and clinical studies.

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.

Effects of experimental exposure to zearalenone on reproductive system morphometry, plasma oestrogen levels, and oocyte quality of beef heifer.

The aim of the present study was to evaluate the effects of zearalenone (ZEA) on the reproductive system morphometry, oestrogen (E2) levels and oocyte quality of beef heifers. Twenty non-pregnant purebred Nellore (Bos indicus) heifers [age, ≥18 months; initial body weight, 348 ± 30 kg (mean ± standard deviation)] were used. The animals were randomly divided into experimental group and a control group of 10 animals each. Group experimental was administered 300 ppb ZEA per os for 98 days, and the control group was administered placebo per os for 98 days. The administration of ZEA was carried out daily by adding mycotoxin to the diet. All heifers were evaluated weekly via rectal ultrasound examinations (12 weeks). Diameters of the right and left uterine horns, right and left ovaries, largest antral follicle and corpus luteum were measured. Vulva size was also measured. Blood samples were collected to estimate E2 levels. At the end of 12 weeks, the heifers were slaughtered, and the ovaries were sent to the laboratory for in vitro embryo production. A completely randomized design was adopted, and repeated measures analysis of variance (p < .05) was performed (except for oocyte quality). Vulva size (p = .0985); diameters of uterine horns (p = .0522), ovaries (p = .6955), antral follicles (p = .6355) and corpus luteum (p = .3808); and E2 levels (p = .3379) were not affected by the treatments. ZEA-contaminated diet significantly reduced (p = .05) the proportion of viable oocytes (49.4%, n = 207) compared with the control diet (59.9%, n = 222); however, the blastocyst rate did not differ between the groups (p = .9418). The results indicate that contamination of beef heifer's diet with 300 ppb ZEA affected neither morphometric parameters nor plasma oestrogen levels; however, ZEA contamination was detrimental to oocyte quality.

Maternal Reproductive Toxicity of Some Essential Oils and Their Constituents.

Even though several plants can improve the female reproductive function, the use of herbs, herbal preparations, or essential oils during pregnancy is questionable. This review is focused on the effects of some essential oils and their constituents on the female reproductive system during pregnancy and on the development of the fetus. The major concerns include causing abortion, reproductive hormone modulation, maternal toxicity, teratogenicity, and embryo-fetotoxicity. This work summarizes the important studies on the reproductive effects of essential oil constituents anethole, apiole, citral, camphor, thymoquinone, trans-sabinyl acetate, methyl salicylate, thujone, pulegone, ß-elemene, ß-eudesmol, and costus lactone, among others.

Augmentation of the Female Reproductive System Using Honey: A Mini Systematic Review.

Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in vivo on the FRS remain unclear. This review aims to investigate the current literature on the effects of HS on the FRS, particularly on the sex hormone profile and reproductive organs (uterus and vagina). A systematic literature search using Scopus, MEDLINE via Ovid and Cochrane Library databases was conducted. Records were screened and identified for preclinical and clinical studies addressing the effects of HS on the FRS. Data on populations, interventions, outcomes and methodological quality were extracted. Studies were synthesised using tables and written summaries. Of the 198 identified records, six fulfilled the inclusion criteria. All six records were used for data extraction: two experimental studies using rats as the model organism and four human clinical studies of honey on female reproductive health. HS elevated the progesterone levels, restrained body weight increase, prevented uterine and vaginal atrophies in ovariectomised rats, attenuated symptoms of candidiasis and improved oxidative status in patients. Current evidence shows that short-term HS following surgical or physiological menopause exerts an oestrogenic, antioxidant and anti-inflammatory effect on the FRS. However, insufficient long-term studies preclude any definitive conclusions.

Recombinant protein subunit vaccine reduces puerperal metritis incidence and modulates the genital tract microbiome.

The objective of this study was to evaluate the efficacy of 3 vaccine formulations containing proteins (FimH, leukotoxin, and pyolysin), inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes), or both, in the prevention of postpartum uterine diseases. A randomized clinical trial was conducted at a commercial dairy farm; 800 heifers were assigned into 1 of 4 different treatment groups: control, vaccine 1 (bacterin and subunit proteins), vaccine 2 (bacterin), and vaccine 3 (recombinant subunit proteins), and each heifer received a subcutaneous injection of its respective treatment at 240 ± 3 and 270 ± 3 d of gestation. Vaccination significantly reduced the incidence of puerperal metritis when compared with control (9.1% vs. 14.9%, respectively; odds ratio 0.51). Additionally, vaccine 3 was found to reduce the incidence of puerperal metritis when compared with the control (8.0% vs. 14.9%, respectively; odds ratio 0.46). Reproduction was improved for metritic cows that were vaccinated, and the effect was stronger for cows that were treated with vaccine 3. In general, vaccination decreased the total vaginal bacterial load and decreased the vaginal load of F. necrophorum by 9 d in milk. Vaccination reduced the prevalence of puerperal metritis in the first lactation of dairy cows, leading to less metritic disease and improved reproduction.

Low-dose in utero exposure to finasteride promotes developmental changes in both male and female gerbil prostates.

The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers.

Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system.

BACKGROUND: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats. METHODS: Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups. RESULTS: In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup-treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure. CONCLUSIONS: The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female.

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats.

Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats. HIGHLIGHTS: Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats. In the uterus, expression of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure, In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.

Use of Growth Factors for Vulvo/Vaginal Bio-Stimulation.

Vulvo-vaginal atrophy as a main symptom of the Genito Urinary Syndrome of Menopause (GSM) is a consequence of aging, particularly after menopause as a result of follicular ovarian follicle depletion and consequently low estrogen levels. Anatomical structures derived from the urogenital sinus, such as the distal urethra trigone and vestibule, are the most affected areas because of the high concentrations of alfa- and beta-estrogen receptors. The most common symptoms associated with vulvo-vaginal atrophy are dyspareunia, vaginal dryness, irritation, recurrent urinary tract infection and urinary incontinence, which negatively affect the patient's quality of life and sexuality. The purpose of this pilot study was to evaluate a protocol with topical growth factors that seeks to activate collagen and elastin at a molecular level, and thus restore all vaginal functions such as secretion, absorption, elasticity, lubrication and vaginal epithelium thickness.

The development of a silicone vaginal ring with a prostaglandin analogue for potential use in the treatment of canine reproductive disorders.

In veterinary medicine, vaginal rings (VRs) are rarely used. However, there are diseases of female dogs' reproductive system which represent a suitable possibility for their usage. An example of such a disease is canine pyometra which can be treated by lipophilic prostaglandin drugs, unfortunately with harmful side effects after systemic administration. The aim of the study was to prove that the matrix VR based on silicone and channel-forming substance can be successfully used as a carrier for a three-day delivery of prostaglandin E2 (PGE2). Based on an in-vitro release study, an optimum channel-forming substance and its concentration were selected. The results were implemented during the construction of VR from the medical grade silicone DDU-4840 with PGE2 (5 mg). Glucose anhydrous in the 30% concentration was chosen as the most functional channel-forming substance due to synergism of osmotic activity and solubility. The DDU-VR containing PGE2 and 30% of glucose anhydrous exhibited excellent mechanical characteristics and ensured 29% drug release through water-filled channels in first-order kinetic manner. This is eight times higher than a sample without glucose where molecular diffusion through the silicone matrix was dominating the release mechanism. Moreover, drug-free VRs were tested for mechanical resistance and the design of removal thread.

[Effect of Tripterygium Glycosides Tablets on reproductive toxicity in female rats with â ¡ type collagen induced arthritis].

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.

Hormone-responsive genes in the SHH and WNT/ß-catenin signaling pathways influence urethral closure and phallus growth.

Environmental endocrine disruptors (EEDs) that affect androgen or estrogen activity may disrupt gene regulation during phallus development to cause hypospadias or a masculinized clitoris. We treated developing male tammar wallabies with estrogen and females with androgen from day 20-40 postpartum (pp) during the androgen imprinting window of sensitivity. Estrogen inhibited phallus elongation but had no effect on urethral closure and did not significantly depress testicular androgen synthesis. Androgen treatment in females did not promote phallus elongation but initiated urethral closure. Phalluses were collected for transcriptome sequencing at day 50 pp when they first become sexually dimorphic to examine changes in two signaling pathways, sonic hedgehog (SHH) and wingless-type MMTV integration site family (WNT)/ß-catenin. SHH mRNA and ß-catenin were predominantly expressed in the urethral epithelium in the tammar phallus, as in eutherian mammals. Estrogen treatment and castration of males induced an upregulation of SHH, while androgen treatment downregulated SHH. These effects appear to be direct since we detected putative estrogen receptor α (ERα) and androgen receptor (AR) binding sites near SHH. WNT5A, like SHH, was downregulated by androgen, while WNT4 was upregulated in female phalluses after androgen treatment. After estrogen treatment, WIF1 and WNT7A were both downregulated in male phalluses. After castration, WNT9A was upregulated. These results suggest that SHH and WNT pathways are regulated by both estrogen and androgen to direct the proliferation and elongation of the phallus during differentiation. Their response to exogenous hormones makes these genes potential targets of EEDs in the etiology of abnormal phallus development including hypospadias.

Restless Genital Syndrome (ReGS) Should Be Distinguished From Spontaneous Orgasms: A Case Report of Cannabis-Induced Spontaneous Orgasm.

A case is described of a 40-year-old woman with persistent spontaneous orgasms after use of cannabis and five hours of intense pounding sexual activity. She presented with severe anxiety, in particular suffering from restless genital syndrome (ReGS). However, she did not fulfill any of the five criteria of ReGS. It was concluded that her spontaneous orgasms were the result of the use of cannabis combined with the long duration of previous sexual activity. This finding is not only important for physicians, but also for highly exposed subjects such as those active in the sex industry.

Combined oral contraceptives promote androgen receptor and oestrogen receptor alpha upregulation in the female prostate (Skene's paraurethral glands) of adult gerbils (Meriones unguiculatus).

The aim of this study was to evaluate the effects of cyproterone acetate (CPA) and ethinyloestradiol (EE) alone or in combination on the female prostate of adult gerbils. Adult females were exposed for 21 days to daily oral doses of CPA (1mgkg-1), EE (10µgkg-1) or a combination of CPA and EE. Female prostatic complexes were removed, weighed and subjected to morphological, stereological, immunohistochemical and ultrastructural analyses. CPA treatment caused epithelial atrophy and decreased prostate secretory activity. The EE treatment group showed glandular hyperplasia, a high cell-proliferation index and an increase in androgen and oestrogen receptor α (AR and ERα) immunoreactivity. Combined treatment (CPA+EE) caused adverse effects, such as an increase in cell proliferation, higher AR and ERα immunoreactivity, prostatic intraepithelial neoplasia, cell degeneration and aging. In conclusion, the CPA-only treatment promoted antiandrogenic effects on the female gerbil prostate, whereas EE-only had a potent oestrogenic activity. However, when combined, EE overlapped the effects of CPA, changing the pattern of glandular hormonal regulation and stimulating the development of prostatic lesions in female gerbils.

The impact of electromagnetic radiation (2.45 GHz, Wi-Fi) on the female reproductive system: The role of vitamin C.

The present study investigated the effects of applied continuous 2.45 GHz electromagnetic radiation (EMR), which might cause physiopathological or morphological changes in the ovarian, fallopian tubal, and uterine tissues of rats. We proposed that the addition of vitamin C (Vit C) may reduce these severe effects. Eighteen female Sprague Dawley rats were randomly divided into three groups with six animals in each: Sham, EMR (EMR, 1 h/day for 30 days), and EMR + Vit C (EMR, 1 h/day for 30 days 250 mg/kg/daily). Total oxidant status (TOS) and oxidative stress index (OSI) levels increased ( p = 0.011 and p = 0.002, respectively) in the EMR-only group in ovarian tissues. In all tissues, TOS and OSI levels significantly decreased in the Vit C-treated group in ovarian, fallopian tubal, and uterine tissues ( p < 0.05). Anti-müllerian hormone levels significantly increased in the EMR group ( p < 0.05) and decreased in the Vit C-treated groups. Estrogen (E2) levels were unchanged in the EMR group, as the differences were not statistically significant. Immunohistochemical examination of the ovaries revealed significant increases in Caspase-3 expressions in the epithelial cells of the EMR group ( p < 0.05). In the EMR group, hyperemia was observed in uterine tissues. Also, Caspase-3 and Caspase-8 were significantly increased in the EMR group ( p < 0.001). Caspase-3 was significantly diminished with Vit C application in the ovarian and uterine tissues ( p < 0.05). Caspase-8 was significantly diminished only in uterine tissues ( p < 0.05). These results indicate that prolonged EMR exposure induced physiopathological changes in the ovarian, fallopian tubal, and uterine tissues due to oxidative damage. Under the conditions of this study, Vit C may have protective effects on female reproductive system against oxidative damage.

Pathology of cigarettes on the reproductive system and ameliorative effects of alpha lipoic acid: A rat model study.

Cigarette smoking (CS) has some detrimental effects that occur via oxidative stress (OS). The aim of this work was to demonstrate the pathological and immunohistochemical effects of CS and the protective effects of a strong antioxidant alpha lipoic acid (ALA) on CS-induced genital system changes in a rat model. Twenty-eight female rats were randomly allocated to three groups as control, CS-exposed, and CS-exposed and ALA-treated. Reproductive tract organs were collected for biochemical and pathological examinations. In the CS group, OS markers increased in the tissues of both the ovary and fallopian tubes. Decreased follicle numbers in the ovary, marked cilial loss in the fallopian tubes, and pathologic changes in the uterus were observed in the CS group. Positive calcitonin gene-related peptide (CGRP), caspase 3α, hypoxia-inducible factor 1α (HIF-1α), tumor necrosis factor-α (TNF-α) immunoreactions were observed in uterine tissues and HIF-1α immunoreactions in tubal and uterine epithelial cells of the CS group. ALA reversed all these findings effectively. CS has negative effects on the female reproductive system via HIF-1α in tuba uterina and HIF-1α, HIF-2α, TNF-α, caspase 3, and CGRP in the uterus, and ALA could protect against the negative effects of CS on the female reproductive system.