Abstract
Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm2) of CD45+ leukocytes, CD56+ uNK cells, and CD138+ plasma cells as well as of CD16+ and CD57+ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90–300 CD56+ uNK cells/mm2. uRPL cases were classified in subgroups of low (uRPL-CD56low < 90 cells/mm2), normal (uRPL-CD56normal 90–300 cells/mm2), and high uNK cell counts (uRPL-CD56high > 300 cells/mm2). Some cases from the uRPL-CD56low and uRPL-CD56normal subgroups showed elevated proportions of cytotoxic CD16+ and CD57+ cells in relation to CD56+ cells. In the uRPL-CD56high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.
Highlights
The demise of two or more subsequent clinical pregnancies until the 24th week fulfills the latest strict criteria proposed for diagnosis of recurrent pregnancy loss (RPL) [1,2,3]
Elevated levels of CD16+ and CD57+ cells were observed in around 40% of the unexplained recurrent pregnancy loss (uRPL)-CD56low subgroup. These results show that even cases with reduced numbers of uterine Natural Killer (uNK) cells may have heightened cytotoxic potential
Our study reinforces a link between uRPL and disturbances in the endometrial immune cell profile
Summary
The demise of two or more subsequent clinical pregnancies until the 24th week fulfills the latest strict criteria proposed for diagnosis of recurrent pregnancy loss (RPL) [1,2,3]. RPL poses a series of challenges to reproductive medicine worldwide and constitutes a substantial economic burden. It represents a highly frustrating life event for many couples, and its repetitive nature intensifies the psychological distress experienced [4]. RPL affects 1–5% of women of reproductive age. Documented causes of this multifactorial, heterogeneous disorder include advanced maternal age, parental chromosomal abnormalities, uterine. Many are attributed to immune factors [7,8]. Disturbed endometrial immunoreactivity due to inadequate number and function of endometrial immune cell populations has been associated with uRPL [9,10,11,12]
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