The human Y chromosome harbors genes that are responsible for testis development and also for initiation and maintenance of spermatogenesis in adulthood. The long arm of the Y chromosome (Yq) ...contains many ampliconic and palindromic sequences making it predisposed to self-recombination during spermatogenesis and hence susceptible to intra-chromosomal deletions. Such deletions lead to copy number variation in genes of the Y chromosome resulting in male infertility. Three common Yq deletions that recur in infertile males are termed as AZF (Azoospermia Factor) microdeletions viz. AZFa, AZFb and AZFc. As estimated from data of nearly 40,000 Y chromosomes, the global prevalence of Yq microdeletions is 7.5% in infertile males; however the European infertile men are less susceptible to Yq microdeletions, the highest prevalence is in Americans and East Asian infertile men. In addition, partial deletions of the AZFc locus have been associated with infertility but the effect seems to be ethnicity dependent. Analysis of > 17,000 Y chromosomes from fertile and infertile men has revealed an association of gr/gr deletion with male infertility in Caucasians and Mongolian men, while the b2/b3 deletion is associated with male infertility in African and Dravidian men. Clinically, the screening for Yq microdeletions would aid the clinician in determining the cause of male infertility and decide a rational management strategy for the patient. As these deletions are transmitted to 100% of male offspring born through assisted reproduction, testing of Yq deletions will allow the couples to make an informed choice regarding the perpetuation of male infertility in future generations. With the emerging data on association of Yq deletions with testicular cancers and neuropsychiatric conditions long term follow-up data is urgently needed for infertile men harboring Yq deletions. If found so, the information will change the current the perspective of androgenetics from infertility and might have broad implication in men health.
Embryo Implantation: War in Times of Love Ashary, Nancy; Tiwari, Abhishek; Modi, Deepak
Endocrinology (Philadelphia),
02/2018, Letnik:
159, Številka:
2
Journal Article
Recenzirano
Abstract
Contrary to widespread belief, the implantation of an embryo for the initiation of pregnancy is like a battle, in that the embryo uses a variety of coercive tactics to force its acceptance ...by the endometrium. We propose that embryo implantation involves a three-step process: (1) identification of a receptive endometrium; (2) superimposition of a blastocyst-derived signature onto the receptive endometrium before implantation; and finally (3) breaching by the embryo and trophoblast invasion, culminating in decidualization and placentation. We review here the story that is beginning to emerge, focusing primarily on the cells that are in “combat” during this process.
In the present review, we describe the mechanisms that are involved in implantation of the embryo to the uterus and initiation of pregnancy.
Decidual Control of Trophoblast Invasion Sharma, Shipra; Godbole, Geeta; Modi, Deepak
American journal of reproductive immunology (1989),
March 2016, Letnik:
75, Številka:
3
Journal Article
Recenzirano
Odprti dostop
At the time of implantation, the trophoblast cells of the embryo adhere and then invade into the maternal endometrium and eventually establish placentation. The endometrium at the same time undergoes ...decidualization, which is essential for successful pregnancy. While the NK cells of the decidua have been implicated to play a key role in trophoblast invasion, few evidence are now available to demonstrate a pro‐invasive property of decidual stromal cells. Secretions from decidualized endometrial stromal cells promote invasion of primary trophoblasts and model cell lines by activating proteases and altering expression of adhesion‐related molecules. The decidual secretions contain high amounts of pro‐invasive factors that include IL‐1β, IL‐5, IL‐6, IL‐7, IL‐8, IL‐9, IL‐13, IL‐15, Eotaxin CCL11, IP‐10 and RANTES, and anti‐invasive factors IL‐10, IL‐12 and VEGF. It appears that these decidual factors promote invasion by regulating the protease pathways and integrin expression utilizing the STAT pathways in the trophoblast cells. At the same time the decidua also seem to secrete some anti‐invasive factors that are antagonist to the matrix metalloproteinases and/or are activators of tissue inhibitors of metalloproteinases. This might be essential to neutralize the effects of the invasion‐promoting factors and restrain overinvasion. It is tempting to propose that during the course of pregnancy, the decidua must balance the production of these pro and anti‐invasive molecules and such harmonizing production would allow a timely and regulated invasion.
Background
SARS‐CoV‐2 has infected a large number of pregnant women.
Objective
To compare clinical, perinatal outcomes of women with COVID‐19 from high‐income countries (HICs) and low‐ to ...middle‐income countries (LMICs).
Search strategy
Online databases were searched.
Selection criteria
Original studies on pregnant women with COVID‐19 were included.
Data collection and analysis
Information on clinical presentation, co‐morbidities, pregnancy outcomes, neonatal outcomes, and SARS‐CoV‐2 infection in neonates was extracted.
Main results
The pooled estimate of SARS‐CoV‐2 positive neonates is 3.7%. Symptomatic presentations are less common in LMICs compared to HICs (odds ratio OR 0.38). Diabetes (OR 0.5), hypertension (OR 0.5), and asthma (OR 0.14) are commonly reported from HICs; hypothyroidism (OR 2.2), anemia (OR 3.2), and co‐infections (OR 6.0) are commonly reported in LMICs. The overall risk of adverse pregnancy outcomes is higher in LMICs compared to HICs (OR 2.4). Abortion (OR 6.2), stillbirths (OR 2.0), and maternal death (OR 7.8) are more common in LMICs. Preterm births and premature rupture of membranes are comparable in both groups. Neonatal deaths (OR 3.7), pneumonia (OR 7.5), and neonatal SARS‐CoV‐2 infection (OR 1.8) are commonly reported in LMICs.
Conclusions
In LMICs, pregnant women and neonates are more vulnerable to adverse outcomes due to COVID‐19.
PROSPERO registration no: CRD42020198743.
Synopsis
Pregnant women and newborns in low‐ and middle‐income countries are more vulnerable and will require a rigorous clinical evaluation and proper follow‐up to minimize the adverse impact of COVID‐19.
Monoclonal antibodies (mAbs) are one of the most significant molecules in protein therapeutics. They are employed in the field of immunology, oncology and organ transplant. They have been also been ...employed for alleviating several bacterial and viral infections. Moreover, they have revolutionized the area of targeted therapy and improved the quality of treatments, as compared to other cytotoxic drugs and therapies. mAbs bind to specific molecules on the antigen and exhibit specificity towards that molecule, i.e. epitope. Thus, mAbs have immense opportunity to be explored for personalized therapy. The introduction of targeted mAb-based therapeutics has promoted many important scientific achievements in rheumatology. This has warranted additional investigations for developing newer mAb producing clones, to supplement the limited industrial production of certain mAb therapeutics. In this investigation, an integrative approach comprising optimized expression, selection and expansion was adopted to develop a mammalian cell line expressing mAb against TNF-α.The resulting stable clone is anticipated to serve as an economic alternative to the industrial clones, especially for research purposes. The clone was constructed for development of biosimilar of the highly valued therapeutic antibody, Humira.
Infection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this ...work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening. MVs when instilled vaginally are capable of anterograde transport in mouse reproductive tract. Intra-amniotic injections of GBS MVs in mice led to upregulation of pro-inflammatory cytokines and inflammation mimicking features of chorio-amnionitis; it also led to apoptosis in the chorio-decidual tissue. Instillation of MVs in the amniotic sac also resulted in intrauterine fetal death and preterm delivery. Our findings suggest that GBS MVs can independently orchestrate events at the feto-maternal interface causing chorio-amnionitis and membrane damage leading to preterm birth or fetal death.
Purpose
Endometriosis is recognized as a steroid hormone-dependent disorder. However, controversies exist regarding the status of the steroid hormone receptor expression in endometriotic tissues. The ...purpose of this study was to determine the ontogeny of cellular changes in the expression of estrogen receptors (ERα, ERβ), G protein-coupled estrogen receptor 1 (GPER1), and progesterone receptors (PRs) in endometriosis using a mouse model.
Methods
We used the autologous uterine tissue transfer mouse model and studied the mRNA and protein expression of ERα, ERβ, GPER1, and PR in ectopic lesions at 2, 4, and 8 weeks of induction of endometriosis.
Result
As compared to endometrium of controls, in the ectopic endometrium, ERα is reduced while ERβ was elevated in stromal cells; however, Gper1 and PR levels are reduced in both stromal and epithelial cells in a time-specific manner. There is a high inter-animal variation in the levels of these receptors in ectopic endometrium as compared to controls; the levels also varied by almost 100-fold within the same lesion resulting in “micro-heterogeneity.” The expression of all these receptors also deferred between two lesions from the same animal.
Conclusion
In the endometriotic tissue, there is extensive inter-animal and intra-lesion heterogeneity in the expression of ERα, ERβ, GPER1, and PR. These changes are not due to the influence of the peritoneal environment but appear to be tissue intrinsic. We propose that the variable outcomes in hormonal therapy for endometriosis could be possibly due to heterogeneity in the expression of steroid hormone receptors in the ectopic endometrium.
Background & objectives: The PregCovid registry was established to document the clinical presentations, pregnancy outcomes and mortality of pregnant and post-partum women with COVID-19.
Methods: The ...PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across the State of Maharashtra, India. Data of 4203 pregnant women collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) was analyzed.
Results: There were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The proportion of pregnancy/foetal loss including stillbirths was six per cent. Five hundred and thirty-four women (13%) were symptomatic, of which 382 (72%) had mild, 112 (21%) had moderate, and 40 (7.5%) had severe disease. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications. The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths.
Interpretation & conclusions: The study demonstrates the adverse outcomes including severe COVID-19 disease, pregnancy loss and maternal death in women with COVID-19 in Maharashtra, India.
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