Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source of estradiol through active aromatase. Steroidogenic factor-1 (SF1) is a key transcription factor that promotes aromatase synthesis. The expression of SF1 and ESRβ is enhanced by the demethylation of their promoter in progenitor cells of the female reproductive system. High local concentrations of estrogen are involved in the chronic inflammatory environment favoring the implantation and development of endometriotic implants. Similar local conditions can promote, directly and indirectly, the appearance and development of genital cancer. Recently, certain components of the microbiota have been identified as potentially promoting a high level of estrogen in the blood. Many environmental factors are also suspected of increasing the estrogen concentration, especially prenatal exposure to estrogen-like endocrine disruptors such as DES and bisphenol A. Phthalates are also suspected of promoting endometriosis but throughmeans other than binding to estradiol receptors. The impact of dioxin or tobacco seems to be more controversial.

Women’s fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women’s fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women’s fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.

Hereditary hemochromatosis is a genetic disease that progresses silently. This disease is often diagnosed late when complications appear. Hypogonadotropic hypogonadism (HH) is one of the classical complications of hemochromatosis. Its frequency is declining probably because of earlier diagnosis and better informed physicians. Certain symptoms linked to HH can have an impact on a patient’s sexuality, such as decreased libido, erectile dysfunction, and impairment of ejaculation, as well as on his reproductive capacities. This review is based on an online search in English, French and German language publications found in PubMed/Medline, up to 23 September 2016 using the following key word: Male infertility, Hypogonadotropic Hypogonadism, Hereditary Hemochromatosis. Thirty-four papers met these inclusion criteria. This review describes the impact of iron overload on male fertility, resulting in hypogonadotropic hypogonadism and proposes treatment modalities.

In the context of a continuously increased delay of motherhood and of an increase of the incidence of premature ovarian failure, it is of the greatest interest to dispose of a predictive marker of the duration of the fertility window. Unfortunately, current available markers of women’s fertility (hormonal rates or echography count of small follicles) have a poor predictive value of premature ovarian failure. In the last ten years, some studies have suggested that telomere length may be correlated with premature ovarian failure, but the results of these studies are contradictory.In accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this systematic review of the literature selected studies evaluating telomere length or telomerase activity in granulosa cells and/or in leukocytes as a premature ovarian failure marker.Five publications (252 premature ovarian failure patients) were included in this review of experimental evidence. Two of them studied telomere length and/or telomerase activity in granulosa cells and 4 in leukocytes in women with premature ovarian failure. For each study, authors determined if there was a positive or a negative correlation between telomeric parameters and premature ovarian failure.3 studies (178 premature ovarian failure patients) found shorter telomere length in granulosa cells and/or leukocytes and/or lower telomerase activity in premature ovarian failure patients. 2 studies (74 premature ovarian failure patients) presented contradictory results about the correlation of leucocyte telomere length with premature ovarian failure.Shorter telomeres and diminished telomerase activity in granulosa cells appear to be associated with ovarian insufficiency. However, the number of studies and of subjects within are low and the methodology questionable. The confirmation of these results is essential with more subjects, better defined populations and more adapted methodology, in order to consider telomere length in granulosa cells and/or in leucocytes as an early and reliable marker for the decline of ovarian function.

Purpose: Bardet-Biedl syndrome (BBS) is a ciliopathy with a wide spectrum of symptoms due to primary cilia dysfunction, including genitourinary developmental anomalies as well as impaired reproduction, particularly in males. Primary cilia are known to be required at the following steps of reproduction function: (i) genitourinary organogenesis, (ii) in fetal firing of hypothalamo-pituitary axe, (iii) sperm flagellum structure, and (iv) first zygotic mitosis conducted by proximal sperm centriole. BBS phenotype is not fully understood.Methods: This study explored all steps of reproduction in 11 French male patients with identified BBS mutations.Results: BBS patients frequently presented with genitourinary malformations, such as cryptorchidism (5/11), short scrotum (5/8), and micropenis (5/8), but unexpectedly, with normal testis size (7/8). Ultrasonography highlighted epididymal cysts or agenesis of one seminal vesicle in some cases. Sexual hormones levels were normal in all patients except one. Sperm numeration was normal in 8 out of the 10 obtained samples. Five to 45% of sperm presented a progressive motility. Electron microscopy analysis of spermatozoa did not reveal any homogeneous abnormality. Moreover, a psychological approach pointed to a decreased self-confidence linked to blindness and obesity explaining why so few BBS patients express a child wish.Conclusions: Primary cilia dysfunction in BBS impacts the embryology of the male genital tract, especially epididymis, penis, and scrotum through an insufficient fetal androgen production. However, in adults, sperm structure does not seem to be impacted. These results should be confirmed in a greater BBS patient cohort, focusing on fertility.

The molecular mechanism of human embryo implantation is poorly understood. The role of MUC4 mucin, present in endometrial epithelium, has never been explored, and results obtained in animal studies strongly suggest a role in implantation. We investigated the role of MUC4 in human embryo implantation. We analysed the MUC4 variable number of tandem repeat (VNTR) polymorphism in three populations by Southern blot analysis: spontaneously fertile patients (C), infertile patients with repeated unexplained implantation failures after IVF (IF) and patients with a child after IVF (IVF-C). We found no differences in the size or allelic distribution of MUC4 VNTR between these three populations. We also examined, in IVF-C and IF groups, the endometrial expression of MUC4 mRNA as well as the expression of the MUC4 glycoprotein together with estrogen receptor (ER) and progesterone receptor (PR). No expression differences could be detected. However, we noticed a pattern of expression for MUC4 protein, which is limited to patches of cells in the luminal and glandular epithelium. We conclude that the different-sized MUC4 alleles do not interfere with implantation. The absence of coexpression of MUC4 and the steroid receptors suggests that MUC4 expression is not directly regulated by steroids.