Female Fertility Disorders Research Articles

Irisin in Reproduction: Its Roles and Therapeutic Potential in Male and Female Fertility Disorders.

The current study focused on identifying the potential of irisin in mammalian reproduction. The established role of irisin, a proteolytic product of FNDC5, in adipose tissue browning, energy metabolism, and thermogenesis suggests its role in reproductive health, often disturbed by metabolic imbalances. Various studies on mice demonstrated irisin's role in improving spermatogenesis, sperm count, and testosterone levels by influencing the hypothalamus-pituitary-gonadal axis. Moreover, in females, there is a fluctuation in levels of irisin during critical reproductive stages, including menstrual cycles, puberty, and pregnancy. Conditions like pregnancy complications, precocious puberty, and polycystic ovary syndrome (PCOS) are found to have an association with abnormal irisin levels. The potential role of irisin in endometrial receptivity and preventing endometritis is also discussed in this review. Overall, the influence of irisin on female and male reproduction is evident from various studies. However, further research is needed to elucidate irisin mechanism in reproduction and its potential as a therapeutic or diagnostic tool for reproductive dysfunctions and infertility.

A Human Homozygous HELQ Missense Variant Does Not Cause Premature Ovarian Insufficiency in a Mouse Model.

Disruption of meiosis and DNA repair genes is associated with female fertility disorders like premature ovarian insufficiency (POI). In this study, we identified a homozygous missense variant in the HELQ gene (c.596 A>C; p.Gln199Pro) through whole exome sequencing in a POI patient, a condition associated with disrupted ovarian function and female infertility. HELQ, an enzyme involved in DNA repair, plays a crucial role in repairing DNA cross-links and has been linked to germ cell maintenance, fertility, and tumour suppression in mice. To explore the potential association of the HELQ variant with POI, we used CRISPR/Cas9 to create a knock-in mouse model harbouring the equivalent of the human HELQ variant identified in the POI patient. Surprisingly, Helq knock-in mice showed no discernible phenotype, with fertility levels, histological features, and follicle development similar to wild-type mice. Despite the lack of observable effects in mice, the potential role of HELQ in human fertility, especially in the context of POI, should not be dismissed. Larger studies encompassing diverse ethnic populations and alternative functional approaches will be necessary to further examine the role of HELQ in POI. Our results underscore the potential uncertainties associated with genomic variants and the limitations of in vivo animal modelling.

Herbal treatment options for female fertility disorders: a systematic review of clinical trials

Herbal treatment options for female fertility disorders: a systematic review of clinical trials

Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

The Hepatokine FGF21 Increases the Human Spermatozoa Motility.

Lifestyle, environment and excess body weight are not only associated with an increased risk of metabolic disorders, such as type 2 diabetes, but also to other pathological processes, such as infertility. A hormone produced mainly by the liver called fibroblast growth factor 21 (FGF21) is closely linked to the energy status and is increased in patients suffering from obesity or insulin resistance. Recently, FGF21 has been shown to be associated with female fertility disorders, but no or few data about the role of FGF21 on human male fertility has been described. In the present study, FGF21 was measured in the seminal fluid at a lower level in comparison to the blood level. Thus, in the present in vitro study, we aimed to decipher the FGF21 system in human semen. To evaluate the putative role of FGF21 on spermatozoa function, we incubated human spermatozoa with increasing concentrations of recombinant human FGF21. The FGF21 in seminal fluid is potentially produced by male reproductive tract tissues. In spermatozoa, the FGF21 signal was transduced by the two main receptors FGFR1-c and FGFR3 and the cofactor β-klotho, which are colocalized in the middle piece of spermatozoa and stimulated the PI3K/Akt and MAPK pathways. Finally, in vitro treatment by FGF21 significantly increased sperm motility and ATP levels. Concomitantly, exposure to FGF21 improved the oxidative stress, as a lower ROS level was observed. Overall, these results seem to indicate that the metabolic factor, FGF21, positively modifies the activity and quality of the parameters of human spermatozoa.

Роль імуноглобуліну А при запальному процесі за участю нейтрофілів

Neutrophils, as effector cells of acute inflammation, play a significant role in tissue homeostasis maintaining through participation in innate and adaptive immune responses. Class A immunoglobulins (IgA) are the most common antibodies in mucous membranes, as well as the second most abundant in the blood and are considered one of the powerful regulators of the functional activity of neutrophils. The review examines the effect of IgA on the inflammatory process involving neutrophils, which involves both the nonspecific innate immune response and the antigen-dependent response of the immunity. Depending on the situation, IgA is able to initiate both pro- and anti-inflammatory neutrophil response. Examples of diseases with IgA-dependent disorders in the regulation of neutrophil activity, as well as approaches to their correction are given. Particular attention has been paid to the possible association of some diseases in which neutrophils are overactivated by IgA immune complexes with female fertility disorders.

The Role of ApoE Expression and Variability of Its Glycosylation in Human Reproductive Health in the Light of Current Information.

Apolipoprotein E (ApoE), a 34-kDa glycoprotein, as part of the high-density lipoprotein (HDL), has antioxidant, anti-inflammatory and antiatherogenic properties. The variability of ApoE expression in the course of some female fertility disorders (endometriosis, POCS), and other gynecological pathologies such as breast cancer, choriocarcinoma, endometrial adenocarcinoma/hyperplasia and ovarian cancer confirm the multidirectional biological function of ApoE, but the mechanisms of its action are not fully understood. It is also worth taking a closer look at the associations between ApoE expression, the type of its genotype and male fertility disorders. Another important issue is the variability of ApoE glycosylation. It is documented that the profile and degree of ApoE glycosylation varies depending on where it occurs, the type of body fluid and the place of its synthesis in the human body. Alterations in ApoE glycosylation have been observed in the course of diseases such as preeclampsia or breast cancer, but little is known about the characteristics of ApoE glycans analyzed in human seminal and blood serum/plasma in the context of male reproductive health. A deeper analysis of ApoE glycosylation in the context of female and male fertility will both enable us to broaden our knowledge of the biochemical and cellular mechanisms in which glycans participate, having a direct or indirect relationship with the fertilization process, and also give us a chance of contributing to the enrichment of the diagnostic panel in infertile women and men, which is particularly important in procedures involved in assisted reproductive techniques. Moreover, understanding the mechanisms of glycoprotein glycosylation related to the course of various diseases and conditions, including infertility, and the interactions between glycans and their specific ligands may provide us with an opportunity to interfere with their course and thus develop new therapeutic strategies. This brief overview details some of the recent advances, mainly from the last decade, in understanding the associations between ApoE expression and some female and male fertility problems, as well as selected female gynecological diseases and male reproductive tract disorders. We were also interested in how ApoE glycosylation changes influence biological processes in the human body, with special attention to human fertility.

The role of free radicals and antioxidants in male and female fertility disorders: review study

Introduction: Free radicals play a double role in the body based on their physiological level and can be beneficial or harmful. This review study was performed with aim to evaluate the cellular and molecular mechanisms of oxidative stress on spermatogenesis and oogenesis and the role of using antioxidant in improving fertility in men and women. Methods: In this review study, the issues related to the role of free radicals and antioxidants on male and female fertility disorders were searched in the Persian and English databases including: Elsevier, Scopus, Irandoc, SID, Iran medex, Sciencedirect, Pubmed, GoogleScholar and Web of Science using the keywords of free radicals, male infertility, female infertility, and antioxidants without any time limitation. Finally, 63 studies entered the review study. Results: The excessive production of free radicals in the male reproductive system causes damage to DNA, RNA, and sperm membranes, and ultimately disrupts spermatogenesis. It also causes disorders in the female genital tract including defect in oocyte development and maturation, follicular growth and function of corpus luteum. Conclusion: According the results of previous studies, using antioxidants may remove the harmful effects of free radicals on male and female fertility.

Survival analyses in Holstein cows considering direct disease diagnoses and specific SNP marker effects

The aim of the present study was to infer influences of health disorders and of specific SNP markers on longevity in Holstein cows via survival analyses. Longevity was defined as the length of productive life (LPL), reflecting the interval from first calving until the culling or censoring date. In this regard, we considered longevity records from 129,386 Holstein cows from 57 large-scale herds, with calving dates in first parity between January 2004 and December 2017 (30.27% censored records). We selected specific diseases from the overall categories claw disorders, udder diseases, metabolic disorders, and female fertility disorders within 3 stages of parities 1, 2, and 3. Lactation stage 1 was the period from calving to days in milk (DIM) 59, lactation stage 2 from DIM 60 to DIM 299, and lactation stage 3 from DIM 300 to the next calving date. The effects of the diseases on culling risk ratios were estimated via Weibull proportional hazards models. In this regard, we used 3 different modeling strategies. In modeling strategy M1S, binary diseases from different parities and lactation stages for the same diagnosis were modeled as explanatory variables in separate runs. Modeling strategy M3S included diseases for the same diagnosis from stage 1, 2, and 3 in the same parity simultaneously. Modeling strategy M9S implied consideration of diseases for the same diagnosis from different lactation stages and from all 3 parities simultaneously. The effect of the same diseases on culling risks from M1S and M3S were similar, with increasing detrimental effect of diseases recorded in later lactation stages and parities. The strongest disease effect on LPL was detected for clinical and subclinical mastitis recorded in the middle of the third lactation, with culling risks of 2.59 and 2.40, respectively, and for claw disorders from the last stage in third lactation (culling risks in the range from 1.85 to 2.29). The effective (ignoring the proportion of censoring; heff2) and equivalent (considering proportion of censoring; hequ2) heritabilities for LPL when considering diseases from specific stages in parities 1 and 3 were quite low ( heff2 0.02 - 0.17; hequ2 0.01 - 0.12). Simultaneous consideration of same disease diagnoses across stages (M3S) and across lactations (M9S) contributed to a LPL heritability increase. Ignoring diseases as explanatory variables in survival analyses was generally associated with a decline of genetic LPL variances and LPL heritabilities. A genome-wide association study for LPL was based on estimated de-regressed proofs from 17,362 genotyped cows. Six SNP located on Bos taurus autosomes 1, 4, 10, 13, and 28 were significantly associated with LPL (using a 5% false discovery rate). Gene annotations via Ensembl identified the 4 potential candidate genes ETV1, ONECUT1, MACROD2, and SIRT1, which directly (via disease resistance mechanisms) or indirectly (via milk productivity) influence dairy cow longevity. Genotypes of the 6 significantly associated SNP were considered as fixed effects in Weibull hazards models, but their effects on culling risks were nonsignificant. Heritabilities for LPL from all SNP-based survival models considering the single SNP separately or the 6 SNP simultaneously were 0.05 (hequ2) and 0.12 (heff2). The small number of significantly associated SNP in genome-wide associations and the minor effect of specific SNP on LPL in survival analyses underline the polygenetic nature of longevity.

Effect of ionizing radiation on the female reproductive system.

The tendency towards postponement of maternity implies a greater exposure of female germ cells to damaging environmental effects, including ionizing radiation (IR). Progress in paediatric oncology, based on the use of radiotherapy, also implies the occurrence of gonadal dysfunctions and subsequent female fertility disorders. Therefore, it seems justifiable to systematize the state of knowledge concerning the effect of IR on the female reproductive system. A considerable part of studies concerning the effect of IR on female germ cells have been conducted on animals. Their extrapolation to humans is hindered because in animal studies high acute exposures are applied, which do not reflect human environmental exposures characterized by chronic low dose exposure. Studies on animals provide a heterogenous image, which hinders the formulation of unequivocal conclusions and indicates that radiosensitivity depends, i.a. on IR dose, stage of development of oocytes, the applied marker of the effects of IR, or on the species. LD50 of human oocytes is estimated to be below 2 Gy. The effect of IR depends, i.a. on the dose fractionation and the age (older women are more radiosensitive). In females, the effective sterilizing dose is: at birth 20.3 Gy, at 10 years 18.4 Gy, at 20 years 16.5 Gy, whereas at 30 years 14.3 Gy, which is associated with the available pool of ovarian follicles. Within the range of low doses received as a result of environmental exposure to IR, there is no evidence for the occurrence of either adverse pregnancy outcomes, nor fertility disorders in females. These effects may be related to the cancer radiotherapy, or exposure to high IR doses during nuclear accidents.

Investigation of soluble anti-Müllerian hormone receptor type 2 as a biomarker for diagnosis of female fertility disorders.

The ectodomain of the anti-Müllerian hormone (AMH) type 2 receptor is shed by proteases under certain conditions, which makes it measurable in the blood. The aim of this study was to identify correlations of soluble anti-Müllerian hormone receptor type 2 (sAMHR2) with other sex hormone concentrations and to assess whether sAMHR2 may serve as a new biomarker in fertility disorders. In a retrospective cross-sectional study of women (n=186) with different gynaecological-endocrinological disorders, mixed-effect models were used to analyse the correlation with established diagnostic hormone tests. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance. There was a strong correlation of sAMHR2 with LH (r = 0.898) and FSH (r = 0.846) and a moderate correlation of AMH with testosterone (r = 0.666) and androstenedione (r = 0.696) (all P<0.001). In diagnoses of polycystic ovary syndrome (PCOS), AMH showed the best performance (area under the curve [AUC] 0.981, cut-off 4ng/ml) with 96% sensitivity and 94% specificity. sAMHR2 concentrations and sAMHR2/AMH ratios were elevated in women with ovarian insufficiency, compared with all other study groups, including post-menopausal women on hormone replacement therapy. Highest sensitivity and specificity (100% and 98.2%, respectively) were achieved with sAMHR2/AMH ratio for the diagnosis of post-menopausal status (cut-off 68.85). The sAMHR2/AMH ratio (AUC 0.997) had a better performance than sAMHR2 (AUC 0.947), FSH (AUC 0.989) and LH (AUC 0.967). The sAMHR2/AMH ratio may serve as a useful biomarker for infertility diagnostics to identify post-menopausal women.

Genetic parameters for body weight from birth to calving and associations between weights with test-day, health, and female fertility traits

A data set including 57,868 records for calf birth weight (CABW) and 9,462 records for weight at first insemination (IBW) were used for the estimation of direct and maternal genetic effects in Holstein Friesian dairy cattle. Furthermore, CABW and IBW were correlated with test-day production records and health traits in first-lactation cows, and with nonreturn rates in heifers. Health traits considered overall disease categories from the International Committee for Animal Recording diagnosis key, including the general disease status, diarrhea, respiratory diseases, mastitis, claw disorders, female fertility disorders, and metabolic disorders. For single-trait measurements of CABW and IBW, animal models with maternal genetic effects were applied. The direct heritability was 0.47 for CABW and 0.20 for IBW, and the direct genetic correlation between CABW and IBW was 0.31. A moderate maternal heritability (0.19) was identified for CABW, but the maternal genetic effect was close to zero for IBW. The correlation between direct and maternal genetic effects was antagonistic for CABW (-0.39) and for IBW (-0.24). In bivariate animal models, only weak genetic and phenotypic correlations were identified between CABW and IBW with either test-day production or health traits in early lactation. Apart from metabolic disorders, there was a general tendency for increasing disease susceptibilities with increasing CABW. The genetic correlation between IBW and nonreturn rates in heifers after 56 d and after 90 d was slightly positive (0.18), but close to zero when correlating nonreturn rates with CABW. For the longitudinal BW structure from birth to the age of 24 mo, random regression models with the time-dependent covariate "age in months" were applied. Evaluation criteria (Bayesian information criterion and residual variances) suggested Legendre polynomials of order 3 to modeling the longitudinal body weight (BW) structure. Direct heritabilities around birth and insemination dates were slightly larger than estimates for CABW and IBW from the single-trait models, but maternal heritabilities were exactly the same from both models. Genetic correlations between BW were close to 1 for neighboring age classes, but decreased with increasing time spans. The genetic correlation between BW at d 0 (birth date) and at 24 mo was even negative (-0.20). Random regression model estimates confirmed the antagonistic relationship between direct and maternal genetic effects, especially during calfhood. This study based on a large data set in dairy cattle confirmed genetic parameters and (co)variance components for BW as identified in beef cattle populations. However, BW records from an early stage of life were inappropriate early predictors for dairy cow health and productivity.

Genetic relationships among female fertility disorders, female fertility traits and productivity of Holstein dairy cows in the early lactation period.

Fertility health disorders from the early lactation period including retained placenta (REPLA), metritis (MET), corpus luteum persistence (CLP), anoestria/acyclia (AOEAC) and ovarial cysts (OC), as well as overall disease categories (disorders during the postpartal period (DPP), ovary infertility (OINF), overall trait definition "fertility disorders" (FD)), were used to estimate genetic (co)variance components with female fertility and test-day traits. The disease data set comprised 25,142 Holstein cows from parities 1, 2 and 3 resulting in 43,584 lactations. For disease traits, we used the binary trait definition (sick or healthy) and disease count data reflecting the sum of treatments for the same disease within lactation or within lactation periods. Statistical modelling included single and multiple trait repeatability animal models for all trait combinations within a Bayesian framework. Heritabilities for binary disease traits ranged from 0.04 (OC) to 0.10 (REPLA) and were slightly lower for the corresponding sum trait definitions. Correlations between both trait definitions were almost one, for genetic as well as for permanent environmental effects. Moderate to high genetic correlations were found among puerperal disorders DPP, REPLA and MET (0.45-0.98) and among the ovarian disorders OINF, AOEAC, CLP and OC (0.59-0.99). Genetic correlations between puerperal and ovarian disorders were close to zero, apart from the REPLA-OC association (0.55). With regard to fertility disorders and productivity in early lactation, a pronounced genetic antagonistic relationship was only identified between OC and protein yield. Genetic correlations between fertility disorders and test-day SCS were close to zero. OINF and all diseases contributing to OINF were strongly correlated with the female fertility traits "interval from calving to first service," "interval from service to pregnancy" and "interval from calving to pregnancy." The strong correlations imply that fertility disorders could be included in genetic evaluations of economic fertility traits as correlated predictors. Vice versa, a breeding focus on female fertility traits will reduce genetic susceptibility to OC, CLP and AOEAC.

Phenotypic, genetic, and single nucleotide polymorphism marker associations between calf diseases and subsequent performance and disease occurrences of first-lactation German Holstein cows

A total of 31,396 females born from 2010 to 2013 in 43 large-scale Holstein-Friesian herds were phenotyped for calf and cow disease traits using a veterinarian diagnosis key. Calf diseases were general disease status (cGDS), calf diarrhea (cDIA), and calf respiratory disease (cRD) recorded from birth to 2 mo of age. Incidences were 0.48 for cGDS, 0.28 for cRD, and 0.21 for cDIA. Cow disease trait recording focused on the early period directly after calving in first parity, including the interval from 10 d before calving to 200 d in lactation. For cows, at least one entry for the respective disease implied a score = 1 (sick); otherwise, score = 0 (healthy). Corresponding cow diseases were first-lactation general disease status (flGDS), first-lactation diarrhea (flDIA), and first-lactation respiratory disease (flRD). Additional cow disease categories included mastitis (flMAST), claw disorders (flCLAW), female fertility disorders (flFF), and metabolic disorders (flMET). A further cow trait category considered first-lactation test-day production traits from official test-days 1 and 2 after calving. The genotype data set included 41,256 single nucleotide polymorphisms (SNP) from 9,388 females with phenotypes. Linear and generalized linear mixed models with a logit link-function were applied to Gaussian and categorical cow traits, respectively, considering the calf disease as a fixed effect. Most of the calf diseases were not significantly associated with the occurrence of any cow disease. By trend, increasing risks for the occurrence of cow diseases were observed for healthy calves, indicating mechanisms of disease resistance with aging. Also by trend, occurrence of calf diseases was associated with decreasing milk, protein, and fat yields. Univariate linear and threshold animal models were used to estimate heritabilities and breeding values (EBV) for all calf and cow traits. Heritabilities for cGDS and cRD were 0.06 and 0.07 for cDIA. Genetic correlations among all traits were estimated using linear-linear animal models in a series of bivariate runs. The genetic correlation between cDIA and cRD was 0.29. Apart from the genetic correlation between flRD with cGDS (-0.38), EBV correlations and genetic correlations between calf diseases with all cow traits were close to zero. Genome-wide association studies were applied to estimate SNP effects for cRD and cDIA, and for the corresponding traits observed in cows (flRD and flDIA). Different significant SNP markers contributed to cDIA and flDIA, or to cRD and flRD. The average correlation coefficient between cRD and flRD considering SNP effects from all chromosomes was 0.01, and between cDIA and flDIA was -0.04. In conclusion, calf diseases are not appropriate early predictors for cow traits during the early lactation stage in parity 1.

The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders.

A large number of studies have contributed to understanding the general mechanisms driving ovarian folliculogenesis in humans and show a complex endocrine dialog between the central nervous system, the pituitary and the ovary, integrated by various intraovarian paracrine messages. The role of intraovarian paracrine regulation has acquired more relevance in the recent years owing to the discovery of previously unknown factors, such as the oocyte-derived bone morphogenetic protein (BMP)15. A thorough literature search was carried out in order to summarize what has been reported so far on the role of BMP15, and the BMP15 paralog, growth and differentiation factor 9 (GDF9), in ovarian function and female fertility. Research articles published in English until March 2014 were included. The biological actions of BMP15 include: (i) the promotion of follicle growth and maturation starting from the primary gonadotrophin-independent phases of folliculogenesis; (ii) the regulation of follicular granulosa cell (GC) sensitivity to FSH action and the determination of ovulation quota; (iii) the prevention of GC apoptosis and (iv) the promotion of oocyte developmental competence. The existence of biologically active heterodimers with GDF9, and/or the synergistic co-operation of BMP15 and GDF9 homodimers are indeed relevant in this context. Experimental disruption of the bmp15 gene in mice resulted in a mild fertility defect limited to females, whereas natural missense mutations in ewes cause variable phenotypes (ranging from hyperprolificacy to complete sterility) depending on a fine gene dosage mechanism also involving GDF9. Strong evidence supports the concept that such a mechanism plays an important role in the regulation of ovulation rate across mammalian and non-mammalian species. Following the discovery of sheep fecundity genes, several research groups have focused on alterations in human BMP15 associated with primary ovarian insufficiency (POI) or polycystic ovary syndrome. Several variants of BMP15 are significantly associated with POI supporting their pathogenic role, but the underlying biological mechanism is still under investigation and of great interest in medicine. BMP15 maps to the Xp locus involved in the determination of the ovarian defect in Turner syndrome and significantly contributes to the determination of ovarian reserve. Pioneering studies in women undergoing controlled ovarian stimulation indicate that BMP15 may represent a marker of ovarian response or oocyte quality. BMP15, an oocyte-derived growth and differentiation factor, is a critical regulator of folliculogenesis and GC activities. Variations in BMP15 gene dosage have a relevant influence on ovarian function and can account for several defects of female fertility. The modulation of BMP15 action may have interesting pharmacological perspectives and the analysis of BMP15 may become a useful marker in IVF procedures. Recent outcomes indicate that the close interactions of BMP15/GDF9 have a critical biological impact that should be taken into account in future studies.

Autonomic dysfunction may be an under-recognized cause of female fertility disorders

Female conditions of impaired fertility comprise a heterogeneous group of disorders that are attributed to various anatomic, hormonal and immunologic disturbances. We hypothesize that autonomic dysfunction may be a previously unrecognized factor in female fertility disorders. Emerging physiologic and molecular evidence suggests that autonomic balance varies during normal menstrual cycles with a shift to sympathetic bias during the luteal phase. Furthermore, many diseases associated with autonomic dysfunction show catamenial variations in patterns consistent with a shift to sympathetic bias occurs during the second half of normal menstrual cycles. The shift to sympathetic bias during the normal luteal phase may be an evolutionary adaptation to address the immunologic and physiologic demands for successful implantation and gestation. Through direct modulation of the lymphoid system and activation of the cortisol pathway, sympathetic bias promotes a shift to relative T helper (Th)-2 biased immunity which may favor maternal tolerance of the embryo by attenuating Th-1 mediated interference of implantation. Indeed, a growing body of evidence has implicated abnormal Th balance in fertility disorders, but the link has been attributed to factors other than autonomic function, such as hormonal factors. After implantation, maternal sympathetic bias may further support gestation through physiologic changes necessary to maintain placental perfusion pressure. We propose that insufficient shift to sympathetic bias during the luteal phase, which manifests in inadequate shift towards Th-2 bias and down-regulation of Th-1 function, may be the mechanism of impaired fertility in certain patients. Our hypothesis portends new potential methods to treat fertility disorders by modulating autonomic balance.

New evidence of the influence of exogenous and endogenous factors on sperm count in man

Objective: To examine the association between individual exposures due to occupation, environment and lifestyle on sperm count, we conducted a case-control study among 92 fertile and 73 sub-fertile Caucasian males. Study Design: Data from questionnaires were analysed using simple univariate and multivariate logistic regression models. Results: At risk for oligozoospermia are men exposed to pesticides (odds ratio (OR) 8.4; 95% confidence interval (CI) 1.3–52.1), welding (OR 2.8; CI 0.9–8.7), antibiotic use (OR 15.4; CI 1.4–163), a history of mumps (OR 2.9; CI 1.3–6.7), gastrointestinal complaints (OR 6.2; CI 1.4–26.8), decreased intake of fruits (OR 2.3; CI 1.0–5.1), vegetables (OR 1.9; CI 0.7–5.0), or with female fertility disorders in their families (OR 8.4; CI 1.7–41.9). Unlike other studies, no associations were observed between oligozoospermia and exposure to paint or heat. Conclusion: This study suggests new risk factors oligozoospermia in man and confirms previously reported results from others.